Tuesday, December 31, 2013

Blessings on Your New Year

Happy New Year to all my readers!

Thank you for reading, linking, and referring to this blog over the years. We are now approaching close to 2 million page views, which is simply stunning. Thank you so much; you humble me.

As a New Year's gift back to you, I'd like to share some special music. I love music, especially classical music, and this is one of my favorites.

In Japan, there is a lovely New Year's tradition of participating in a performance of Beethoven's Ninth Symphony (the choral symphony with the famous "Ode to Joy" tune, which was adapted into the church hymn, "Joyful Joyful We Adore Thee"). Supposedly this tradition began back in World War I when German prisoners-of-war played it at a concert for people in Japan. Over time (for many reasons), it developed into an annual tradition there, played all throughout December and culminating in massive New Year's Eve performances.

But while huge concerts are inspiring and impressive, there is something to be said for a slightly more intimate version too. This is an utterly charming video of a flash mob of musicians in Spain performing the best and most familiar bits of the famous last movement of Beethoven's Ninth.

It's not the most polished performance, but who cares? That's not the point. It's all about the exuberance of the music, the pleasure of making communal music together, and the sheer joy of the children and others watching as they are moved by this wonderful piece of music written long ago by a man who couldn't even hear the music out loud anymore but who continued to write for the sake of the beauty he could still hear inside his head.

Enjoy the beautiful music, count your blessings and your joys, and have a wonderful year. Many blessings upon you and yours.

*Want more? If you've got the time, check out the justly-famous 1989 Fall of the Berlin Wall Ode to Freedom concert of Beethoven's Ninth, conducted with transparent and overwhelming emotion by Leonard Bernstein. Part one of the 4th movement is here, and the second half of the movement is here. (If you don't have time for it all, my favorite part is the first four minutes or so of part one!)

Tuesday, December 24, 2013

Treasure This Time Together

Merry Christmas, everyone. Hope you are having a wonderful, happy holiday with your families!

Travel safely, and don't let the stress of travel or preparations impede the enjoyment of your time together. Focus on the important things in the season, not the passing unimportant ones.

Treasure every moment with your loved ones. Life changes quickly; savor your time with your family and friends now because you never know who won't be with you next year. Overlook their quirks where you can, humor or avoid the more challenging folks, forgive where you can, and appreciate people's good qualities as much as possible. Count your blessings and give thanks for the people you love.

Reach out to family and friends you don't know that well so you can build those relationships if possible. Family can be trying sometimes, but they do matter. When they are gone, you never get them back. Make the extra effort to reach out and make connections. Take a chance; you never know what kind of special relationship or memories you might be missing.

Shower love and appreciation on those who matter most. Remember that this time in the children's development will never come again, so take lots of pictures of everyone (including yourself) and spend as much time as you can just being with them and having fun together. It's not about what you are doing, it's about doing it together and making those memories.

Treasure your time together, and cherish your loved ones. Honor the sacredness of the season. Find the joy and hold it close to your heart.

Have a wonderful holiday; the blog will resume after some holiday family time. Merry Christmas and Happy New Year!

Friday, December 20, 2013

Public Perceptions of Obesity Health Messages

Fat shaming is extremely common these days. Just look at some of these "discussions" online and read some of the comments on them (if your sanity can take it). Or watch many weight-loss reality shows (if your blood pressure can take it).

This kind of fat shaming and scolding is the end result of many stigmatizing anti-obesity public health campaigns.

Research shows that public health campaigns that shame and scold fat people have negative effects on the health of fat people. Furthermore, they make fat people less likely to improve health habits or see their care providers regularly.

Perhaps the best approach to improving public health may well be the type that Health At Every Size® suggests ─ placing the emphasis on encouraging healthy habits instead of on losing weight as the main goal.


Int J Obes (Lond). 2013 Jun;37(6):774-82. doi: 10.1038/ijo.2012.156. Epub 2012 Sep 11.
Fighting obesity or obese persons? Public perceptions of obesity-related health messages.
Puhl R, Peterson JL, Luedicke J.  PMID: 22964792
OBJECTIVE: This study examined public perceptions of obesity-related public health media campaigns with specific emphasis on the extent to which campaign messages are perceived to be motivating or stigmatizing. METHOD: In summer 2011, data were collected online from a nationally representative sample of 1014 adults. Participants viewed a random selection of 10 (from a total of 30) messages from major obesity public health campaigns from the United States, the United Kingdom and Australia, and rated each campaign message according to positive and negative descriptors, including whether it was stigmatizing or motivating. Participants also reported their familiarity with each message and their intentions to comply with the message content. RESULTS: Participants responded most favorably to messages involving themes of increased fruit and vegetable consumption, and general messages involving multiple health behaviors. Messages that have been publicly criticized for their stigmatizing content received the most negative ratings and the lowest intentions to comply with message content. Furthermore, messages that were perceived to be most positive and motivating made no mention of the word 'obesity' at all, and instead focused on making healthy behavioral changes without reference to body weight. CONCLUSION: These findings have important implications for framing messages in public health campaigns to address obesity, and suggest that certain types of messages may lead to increased motivation for behavior change among the public, whereas others may be perceived as stigmatizing and instill less motivation to improve health.
J Bioeth Inq. 2013 Mar;10(1):49-57. doi: 10.1007/s11673-012-9412-9. Epub 2013 Jan 4. Primum non nocere: obesity stigma and public health. Vartanian LR, Smyth JM. PMID: 23288439
Several recent anti-obesity campaigns appear to embrace stigmatization of obese individuals as a public health strategy. These approaches seem to be based on the fundamental assumptions that (1) obesity is largely under an individual's control and (2) stigmatizing obese individuals will motivate them to change their behavior and will also result in successful behavior change. The empirical evidence does not support these assumptions: Although body weight is, to some degree, under individuals' personal control, there are a range of biopsychosocial barriers that make weight regulation difficult. Furthermore, there is accumulating evidence that stigmatizing obese individuals decreases their motivation to diet, exercise, and lose weight. Public health campaigns should focus on facilitating behavioral change, rather than stigmatizing obese people, and should be grounded in the available empirical evidence. Fundamentally, these campaigns should, first, do no harm.
Am J Prev Med. 2013 Jul;45(1):36-48. doi: 10.1016/j.amepre.2013.02.010. Public reactions to obesity-related health campaigns: a randomized controlled trial. Puhl R, Luedicke J, Lee Peterson J. PMID: 23790987
BACKGROUND: Despite numerous obesity-related health campaigns throughout the U.S., public perceptions of these campaigns have not been formally assessed. In addition, several recent publicized campaigns have come under criticism in the popular media for reinforcing stigmatization of obese people. Thus, research in this area is warranted...The data were collected online in summer 2012 from a nationally representative sample of American adults (N=1085). INTERVENTION: Participants were randomly assigned to view 10 obesity-related health campaigns that were pretested and publicly criticized as being stigmatizing of obese people, or 10 campaigns that contained more-neutral content...RESULTS: Stigmatizing campaigns were no more likely to instill motivation for improving lifestyle behaviors among participants than campaigns that were more neutral (OR=1.095, 95% CI=0.736, 1.630). Stigmatizing campaigns were also rated as inducing less self-efficacy (adjusted mean difference = -0.171 SD, 95% CI= -0.266, -0.076) and having less-appropriate visual content compared to less stigmatizing campaigns (adjusted difference in probability = -0.092, 95% CI= -0.124, -0.059). These findings remained consistent regardless of participants' body weight, and were generally consistent across sociodemographic predictors. CONCLUSIONS: This study highlights the need for careful selection of language and visual content used in obesity-related health campaigns, and provides support for efforts to portray obese people in a nonstigmatizing manner.
Obesity (Silver Spring). 2007 Jan;15(1):19-23. Internalization of weight bias: Implications for binge eating and emotional well-being. Puhl RM, Moss-Racusin CA, Schwartz MB. PMID: 17228027
OBJECTIVE: This study examined the relationship between internalization of negative weight-based stereotypes and indices of eating behaviors and emotional well-being in a sample of overweight and obese women. Research Method and Procedures: The sample was comprised of 1013 women who belonged to a national, non-profit weight loss organization. Participants completed an on-line battery of self-report questionnaires measuring frequency of weight stigmatization and coping responses to deal with bias and symptoms of depression and self-esteem, attitudes about weight and obesity, and binge eating behaviors. In addition, participants were asked to list the most common weight-based stereotypes and whether they believed them to be true or false. RESULTS: Participants who believed that weight-based stereotypes were true reported more frequent binge eating and refusal to diet in response to stigma experiences compared with those who reported stereotypes to be false. The degree to which participants believed stereotypes to be true or false was not related to types or amount of stigma experiences reported, self-esteem, depression, or attitudes toward obese persons. In addition, engaging in weight loss strategies as a response to bias was not predicted by stereotype beliefs or by actual stigma experiences, regardless of the amount or types of stigma reported. DISCUSSION: These findings suggest that obese individuals who internalize negative weight-based stereotypes may be particularly vulnerable to the negative impact of stigma on eating behaviors and also challenge the notion that stigma may motivate obese individuals to engage in efforts to lose weight. This study highlights a new area of research that warrants attention to better understand weight stigma and its potential consequences for health.
J Health Psychol. 2008 Jan;13(1):131-8. Effects of weight stigma on exercise motivation and behavior: a preliminary investigation among college-aged females. Vartanian LR, Shaprow JG. PMID: 18086724
This study examined the relation between weight stigma, exercise motivation and exercise behavior. One hundred female undergraduates (BMIs [kg/m(2)] 17-38) completed measures of experiences with weight stigma, body dissatisfaction, self-esteem and exercise motivation, and reported on their exercise behavior. Stigma experiences were positively correlated with BMI and body dissatisfaction. Importantly, stigma experiences were related to increased desire to avoid exercise, even when controlling for BMI and body dissatisfaction. Exercise avoidance was in turn related to less frequent strenuous and moderate exercise. These findings suggest that weight stigma (through its impact on avoidance motivation) could potentially decrease physical activity levels.

Wednesday, December 11, 2013

Feedback on the PCOS Series: What Do You Want?

Before we get to the next post in the PCOS series, I'd like to get some feedback on it.

First, are you liking the PCOS series? Is it useful to you? If so, what's been most helpful? The comments have been pretty quiet on this series and I want to know if it's been useful to people. The series is a considerable amount of work and I want to make sure it's worth my time and research effort to put this out there for you. Do you want me to continue the series, or would you rather I focused on something else instead?

Second, if I continue the PCOS series, what would you most like to see in the near future? I have many posts in development (PCOS and hirsutism/acne, PCOS and fertility, PCOS and pregnancy, PCOS and breastfeeding, PCOS and menopause, PCOS and alopecia, PCOS and depression, PCOS and Lifestyle Tweaks, PCOS and alternative medicine, etc.), but it's a matter of prioritizing which ones to work on first. Some are more ready than others, of course, so not all will be ready anytime soon, but it would be nice to know what people are most wanting to explore.

Third, I'd love to have more personal stories of how you deal with PCOS (if you have it). Personal stories really anchor a series like this, especially when there are so many dry facts and stats in the posts. We need the personal stories for balance and perspective. But I can't put them in if I don't have them.

I'm especially looking for stories on how you deal with the challenges of hirsutism, acne, alopecia, and/or depression. Not every person experiences every PCOS symptom, so I think it's really important to share the experiences and wisdom of those who have struggled with those particularly tough symptoms and what has helped them. Women with those symptoms often feel especially isolated, so I really want personal stories on those particular posts.

I'm happy to share your stories without using names so you can speak very frankly about your experiences. In fact, the more honest, the better. Just be sure to give me formal permission to use your story and how you'd like to see it attributed.

I do have a couple of stories of how people use Health At Every Size® techniques to deal with PCOS, but I'd love more stories with that point of view too. I'd love stories on how women with PCOS try to get traditional providers to deal with PCOS in a more size-friendly (or at least weight-neutral) way. In my experience, women are really looking for strategies on that because the traditional approach to PCOS is so incredibly weight-centric.

So please give me your feedback on the PCOS series so far and what you'd like to see for the future. And if you have a story to share about your own experience with PCOS and how you deal with it, I'd love to have more personal voices in the series as well.

You can use the comments section below, or you can email me privately, using the email address in the column to the left.

As always, thanks for reading!

Friday, December 6, 2013

PCOS Treatment of Irregular Cycles: Progesterone Supplements

Poster by Amanda Kohn,www.implementingdesignism.org 
We've been talking about PCOS (Polycystic Ovarian Syndrome).

First we discussed its definition and symptoms, how it presents, its testing and diagnosis, and its possible causes.

Now we are discussing common treatment protocols for PCOS, and the pros and cons of each.

We've already discussed insulin-sensitizing medications like metformin, the TZDs, and inositol.

Then we discussed glucose-lowering medications for those who have developed overt diabetes.

Today, we start discussing treatments for regulating the menstrual cycle.

This mainly includes progesterone treatments and oral contraceptives for bringing on a period.

Today, we discuss progesterone treatments.
Disclaimer: I am not a medical health-care professional. While the following information is based on my best understanding of the research, always do your own research. This information is not a complete explanation of all the risks and benefits of a particular medication, nor is it medical advice about a health condition or treatment. Consult your healthcare provider before making any decisions about your care plan.
Trigger Warning: Passing mention of the possible weight effects of several medications, and passing mention of weight loss as the usual recommended treatment for menstrual irregularity.
Why It's Important to Treat for Menstrual Irregularity

Many women with PCOS experience irregular periods. It is probably the most common symptom of PCOS, and the one that brings the most attention to the syndrome in medical journals (along with infertility).

In a normal menstrual cycle, the lining of the uterus (endometrium) is exposed to various hormones produced by the body, especially estrogen. These hormones cause the lining to thicken and proliferate in anticipation of a possible pregnancy.

Once ovulation occurs, progesterone levels increase strongly in order to help sustain any pregnancy until the developing placenta can take over progesterone production. If pregnancy does not occur, a precipitous drop in progesterone levels will bring on the woman's period to flush out the unneeded extra lining.

Many women with PCOS have abnormally low levels of progesterone. They don't produce enough progesterone to bring on a period and flush out the uterine lining. This, plus egg follicles that don't develop properly, is why many women with PCOS have irregular periods. Some only skip a month now and again, while others may have only a few periods in a year. Still others may go years without a period.

Women with PCOS also tend to be estrogen-dominant, and as a result, the un-flushed uterine lining can be exposed to excessive levels of estrogen for prolonged periods. This can lead to abnormal overgrowth of the uterine lining (endometrial hyperplasia) and eventually, endometrial cancer.

Therefore, one of the most important treatment goals in PCOS is to regulate the menstrual cycle. There are two reasons that this is important:
  • to improve ovulation for the purposes of fertility if children are desired
  • to reduce the overgrowth of the endometrium and thereby reduce the chance for endometrial cancer later in life
The most common medication for regulating the menstrual cycle is the birth control pill, or The Pill. This ensures your body has a period every month. Most doctors see this as the treatment of choice for cycle regulation in PCOS.

However, if you've gone a long time without a period, many doctors will choose to use a progesterone medication first to "flush out" the uterine lining before trying other medications to regulate the cycle.

Although the focus of this series of posts is progesterone treatments and oral contraceptives, there are alternative treatments out there for regulating menstrual cycles. 

These will be covered in more detail in other posts, but can include lifestyle approaches (moderating carb intake, enhancing nutrition, and increasing exercise), acupuncture, herbs like vitex/chasteberry, the previously-discussed insulin-sensitizing medications like metformin or inositol, and perhaps vitamin D supplementation.

Care providers often also strongly promote weight loss for regulating menstrual cycles. This can be effective for some women but studies are often short-term and do not show what happens if weight loss is regained with time (as so often happens), nor do they acknowledge that weight loss can have risks as well as benefits (see the Weight References section of the blog). And while care providers make it sound like a sure thing, weight loss is not effective for regulating the periods in everyone; a number of women with PCOS still experience missed periods even after considerable weight loss. It is another tool that can be considered if you wish, but it's far from the magic bullet that doctors like to pretend it is.

Remember, there is no one "right" treatment protocol. Each woman must find the right combination of treatments that work best for her circumstances.

For some, this may include progesterone treatment to bring on a long-overdue period.

Progesterone Treatment for Menstrual Regularity 

Prometrium, image from Wikimedia
Progesterone supplements are usually used with a woman who hasn't had a menstrual cycle for quite a while. 

How long is too long? Some sources say at least 6 weeks between periods; others say at least six months between periods. The threshold at which progesterone supplements are prescribed will vary from provider to provider, but women should definitely not be going many months or even years between periods.

There are two main types of progesterone treatments for bringing on a period (withdrawal bleeding):
  • Provera is the name of a synthetic type of progesterone (progestin) treatment; the generic name is medroxyprogesterone. This is the progesterone medication most often prescribed by care providers in the past. It is close to but not exactly like the progesterone produced in your own body
  • Prometrium is the name of another progesterone supplement. It is synthesized from plants but is chemically identical to the progesterone made in your body. Some providers are moving to Prometrium more often these days, especially if pregnancy is desired, since Prometrium is safer to use in pregnancy than Provera
These medications have two main purposes for PCOS. They can be used for inducing a period in women who have not cycled on their own for a while and for managing ongoing abnormal uterine bleeding. In addition, they can be used to manage severe menopausal symptoms in older women.

In the interests of space, here we will only discuss their use for bringing on a period in women who have not cycled in a while.


Provera is a synthetic progestin which is similar but not quite identical to your body's own progesterone. Typically, Provera for inducing a period is prescribed as follows:
For the treatment of stopped menstrual periods (amenorrhea) and abnormal bleeding from the uterus, take this drug usually once daily for 5-10 days during the second half of the planned menstrual cycle or as directed by your doctor. Withdrawal bleeding usually occurs within 3-7 days after you stop taking the medication.
Provera comes in 2.5, 5.0, and 10 mg capsules. It's common to take a 5 mg or 10 mg capsule once a day for 5, 7, or 10 days (depending on your doctor's orders) in order to bring on the period. Other sources say to take Provera for 10 to 14 days every one to three months.

Provera works by simulating the high progesterone levels that occur near the end of your menstrual cycle, just before your period begins. It tricks your body into thinking that ovulation has occurred. Stopping the progesterone supplement simulates the drop in progesterone that occurs in a normal cycle when fertilization has not occurred, and should bring on your period within 2 weeks of stopping the medication. However, sometimes women do start their periods while still taking the Provera.

Some care providers only prescribe progesterone supplements periodically in women with PCOS. Others prefer to prescribe it regularly, about every few months, in order to promote a regular period and reduce the risk of endometrial hyperplasia. Discuss your situation with your care provider and decide what the best treatment routine is for you

If you are planning to try to become pregnant soon, you might want to reconsider whether or not to take Provera to bring on a period shortly before fertility treatment. Two recent studies found that taking Provera shortly before trying to conceive made the uterine lining more thin and women less likely to conceive. However, more research is needed to confirm this finding.

Side Effects and Risks of Provera

Side effects of Provera can be considerable, although short-term use for inducing a period is less risky than long-term use for menopause symptoms. The most common short-term symptoms include:
  • dizziness
  • headache 
  • abdominal pain and cramping
  • breast tenderness
Longer-term symptoms can include:
  • breasts that are tender or produce a liquid
  • changes in menstrual flow
  • irregular vaginal bleeding or spotting
  • acne
  • growth of hair on face
  • loss of hair on scalp
  • difficulty falling asleep or staying asleep
  • drowsiness
  • upset stomach
  • weight gain or loss
More uncommon (but serious) symptoms include:
  • pain, swelling, warmth, redness, or tenderness in one leg only
  • slow or difficult speech
  • dizziness or faintness
  • weakness or numbness of an arm or leg
  • shortness of breath
  • coughing up blood
  • sudden sharp or crushing chest pain
  • fast or pounding heartbeat
  • sudden vision changes or loss of vision
  • double vision
  • blurred vision
  • bulging eyes
  • missed periods
  • depression
  • yellowing of the skin or eyes
  • fever
  • hives
  • skin rash
  • itching
  • difficulty breathing or swallowing
  • swelling of the hands, feet, ankles, or lower legs
  • increased blood pressure
Although not always listed as a possible side effect, many women report that they have experienced extreme irritability and mood swings while on progestin medications. This is one of the most distressing side effects for many women.

Some lab animals which were given medroxyprogesterone developed breast tumors, but it is not clear whether this translates to development of breast cancer in humans. Medroxyprogesterone may also increase the chance of blood clots that move to the lungs (pulmonary embolism) or brain (stroke). Again, these risks are more related to long-term use than short-term use, but it's still important to be aware of the possibility.

Contraindications to Provera include prior history of breast, ovarian, or uterine cancer; blood clots; stroke; seizures; migraines; depression; unexplained vaginal bleeding; incomplete miscarriage; asthma; high blood pressure; diabetes; or heart, kidney, or liver disease.

Provera may create negative drug interactions with St. John's Wort, Rifampin, 
aminoglutethimide (Cytadren), certain anti-seizure medications, and other meds. If you are on any drugs (or any herbs), be sure to discuss that with your care provider before taking Provera.


Some care providers promote the use of bio-identical progesterones like Prometrium instead of synthetic progestins. They believe it will more closely mimic the body's natural process and result in better outcomes.

In some research, about 80% of women who took Prometrium (oral micronized progesterone) were able to re-start their periods.

Anecdotally, some women with PCOS report that they have had better results with Prometrium. Many report less moodiness, less dizziness, and fewer PMS-like symptoms. However, while many people have fewer side effects with Prometrium, others have had more. You have to test out which version is better for your body.

Prometrium is taken for the same reasons as Provera. It tricks the body into thinking it has ovulated; withdrawing the Prometrium will cause a drop in progesterone, hopefully triggering the woman's period within about 2 weeks. However, Prometrium is not as potent as Provera, so it needs a much higher dosage.

For bringing on a period, some sources recommend 100-300 mg of Prometrium for the last 10-12 days of what should be a 28-day cycle. Other sources suggest 400-600 mg per day.

For women who experience very strong estrogen dominance and wild fluctuations of symptoms when going on and off progesterone, some care providers recommend a low continuous dose of Prometrium, rather than constantly going on and off the progesterone.

Prometrium is available as an oral capsule, and can also be used as a vaginal suppository. There is a similar form available as an injectable intramuscular progesterone, or as a vaginal gel (Crinone). There may be fewer side effects with the vaginal versions but it can be a bit messy. The oral form might be best taken at bedtime because it can cause significant drowsiness in many women.

One major disadvantage of Prometrium is that it is much more expensive. Provera is available in a generic form so it can be much more affordable.

Provera should not be used if a woman might conceive a pregnancy. It has mild androgenic effects and can negatively affect a developing male fetus. In contrast, Prometrium is often prescribed by care providers to help lessen the risk for miscarriage in early pregnancy (more on that below).

Side Effects and Risks of Prometrium

Prometrium has many of the same side effects as Provera; re-read the above list to review these side effects. It is especially important to watch for possible signs of blood clots or allergic reaction.

The progesterone in Prometrium is micronized and suspended in a peanut oil solution to make it more bioavailable; the injectable form of intramuscular progesterone is suspended in sesame oil. People with peanut allergies need to avoid Prometrium and people with sesame allergies need to avoid intramuscular progesterone.

Although most women have fewer side effects with Prometrium, some women report more, especially dizziness, drowsiness, headache, acne or bloating/fluid retention. Weight gain is not uncommon with prolonged use of any progesterone supplement, but most non-menopausal women with PCOS will not take it long enough to experience this.

Some sources report that ketoconazole, an anti-fungal medication sometimes used for hair loss with PCOS, inhibits the absorption of Prometrium in the liver and therefore may potentiate its effects. However, oral ketoconazole is rarely prescribed these days as the FDA has recently warned of its potential for liver toxicity and adrenal damage. Furthermore, this warning does not extend to ketoconazole shampoo, which is the form used most often with hair loss concerns. It is unclear at this time whether the mere use of the shampoo would potentiate the effects of Prometrium. Discuss this possibility with your provider.

Controversy Over Use in Pregnancy

One big controversy these days is whether or not Prometrium should be given to women in early pregnancy to try and prevent miscarriage. Many providers are quite comfortable with doing this, while others contend it is not beneficial and may carry risks.

Why would Prometrium be given in pregnancy? Progesterone is important is sustaining a pregnancy, and women with PCOS tend to have low progesterone levels and higher miscarriage rates. The hope is that by supplementing progesterone, the risk for miscarriage will be lessened in this group.

In a woman without PCOS, the corpus luteum (the remains of the egg follicle on the ovary) produces progesterone for the pregnancy until the placenta is developed enough to take over progesterone production. Because follicular development tends to be weaker in women with PCOS, they may not produce enough progesterone to sustain a pregnancy. Supplementing progesterone is thought to help lessen the chance for miscarriage. Prometrium is the only viable choice for this because Provera is contraindicated in pregnancy.

However, using progesterone supplements in pregnancy is somewhat controversial. Many care providers do not believe that progesterone supplements are necessary or helpful for preventing miscarriage and will not prescribe them at all. Others regularly prescribe Prometrium for women with PCOS, especially if there is a history of miscarriage. Many providers also prescribe it for women who have gone through In Vitro Fertilization treatments, or for those experiencing threatened miscarriage.

Anecdotally, many women with PCOS who experienced repeated miscarriages report that progesterone supplements helped them to finally carry a pregnancy to term. Therefore there is fierce support for this practice on some PCOS boards.

However, progesterone supplements during pregnancy have occasionally been associated with hypospadias, an abnormal placement of the hole at the end of the penis in male babies. Rare complications have included cases of cleft lip, cleft palate, and cardiac issues. Whether this is true for all progesterone supplements, however, is not clear. Although some Prometrium-related websites caution against its use in pregnancy, it may actually only be the synthetic progesterones like Provera that carry this added risk. Some doctors' websites state outright that natural progesterone does not carry any additional risk, while others state that there may be a small increased risk. If in doubt, discuss this with your provider.

Prometrium is considered a Category B medication in pregnancy. The safest rating is a Category A. Category B means that animal studies have shown no increased risks to the fetus, but that there haven't been enough tests in humans to confirm this lack of harm. Given the natural reluctance of researchers to experiment on pregnant women, this rating is unlikely to change soon, but most providers seem to consider Prometrium a relatively safe drug for early pregnancy.

A 2013 Cochrane Collaboration review of the use of progesterones for preventing miscarriage found no evidence for its routine use in preventing miscarriages. However, in the subgroup of women with a history of repeated miscarriage, progesterones strongly lowered the risk for miscarriage and did not increase the risk for adverse outcomes like birth defects.

Another Cochrane review noted that progesterone supplements strongly lowered the rate of miscarriage in women experiencing threatened miscarriages. Both reviews noted that the research trials were of relatively poor quality and that more research is needed to guide clinicians on this topic.

So the bottom line so far appears to be that progesterone supplements should not be used routinely in all women in order to prevent miscarriage, but that there is probably a role for it under certain conditions, such as a threatened miscarriage or in women with a strong history of recurrent miscarriages.

Whether or not it should be used routinely in women with PCOS and no other risk factors has not been studied adequately. It may behoove women with PCOS to ask their providers to track their progesterone levels early in pregnancy and consider prescribing a natural progesterone if their levels appear low.

One other potential benefit of vaginal progesterone in pregnancy is that some research suggests that it may lower the rate of spontaneous pre-term birth in women with a shortened cervix in the second trimester.

Since the pregnancies of women with PCOS tend to be at increased risk for cervical insufficiency and pre-term birth, it is interesting to speculate whether low progesterone levels may be part of this risk, and whether or not early supplementation with Prometrium or vaginal progesterone may help prevent some cases of preterm birth in this group. However, at this time, this possibility remains speculative.


It is very important that women have regular periods so that the uterine lining does not build up and become cancerous over time.

There are many approaches that can help regulate the menstrual cycle in women with PCOS. For many, just taking metformin is enough to make periods more regular. For some, a lifestyle approach can make periods more regular. Alternative approaches that some find helpful include acupuncture or herbs like vitex (vitex often helps bring the body's hormones into balance and improves progesterone levels). There are also natural progesterone creams that contain much lower levels of progesterone than the medications discussed here and which may be useful for women with only mild progesterone deficiencies.

But some women with PCOS do not cycle even with these approaches. For these women, an oral contraceptive may be needed to have regular periods and prevent endometrial overgrowth. More on that in our next post.

However, if it has been more than a few months since you've had a period, care providers usually want to flush out the endometrium before beginning other treatments. The most common way to do this is to prescribe progesterone to bring on a period. Provera (a synthetic progestin) is the most commonly prescribed form, but Prometrium (a bio-identical progesterone) is gaining favor among many providers because side effects are often less severe.

Bringing on a long-overdue period with progesterone is not an easy process, and many women report significant bloating, cramps, and mood swings, as well as an extremely heavy period afterwards. This can be truly miserable for some women.

Because it can be such a difficult process, some women with PCOS avoid treatment with progesterones, preferring simply to avoid the bother of a period altogether. However, this will increase their long-term risk for endometrial cancer. As tough as it is to endure a long-overdue period, it is important to do so for your long-term health.

Once the endometrial lining has been flushed out, then other approaches to regulating the menstrual cycle can be tried. Lifestyle approaches, herbs, acupuncture and insulin-sensitizing medications can all help address the underlying hormonal imbalances that cause periods to be irregular. If all else fails, an oral contraceptive (The Pill) can be used, although many women with PCOS prefer to avoid this if possible.

Bottom line, women with PCOS need to prevent endometrial hyperplasia by some means or other. What method is best will depend on your individual circumstances and responsiveness, but progesterone can sometimes be part of that treatment strategy.

In addition, bio-identical progesterone may also hold promise for preventing some cases of miscarriage, and perhaps also for preventing some cases of preterm birth, although more study is needed.

Although they certainly carry risks and should not be over-utilized, progesterone supplements definitely have a role to play in treating some aspects of PCOS. 


Books About PCOS
PCOS Information 
General Information about Progesterone for Regulating Cycles
Studies on Provera and PCOS

Obstet Gynecol. 2012 May;119(5):902-8. doi: 10.1097/AOG.0b013e31824da35c. Endometrial shedding effect on conception and live birth in women with polycystic ovary syndrome. Diamond MP, Kruger M, Santoro N, Zhang H, Casson P, Schlaff W, Coutifaris C, Brzyski R, Christman G, Carr BR, McGovern PG, Cataldo NA, Steinkampf MP,Gosman GG, Nestler JE, Carson S, Myers EE, Eisenberg E, Legro RS; Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network. PMID: 22525900
OBJECTIVE: To estimate whether progestin-induced endometrial shedding, before ovulation induction with clomiphene citrate, metformin, or a combination of both, affects ovulation, conception, and live birth rates in women with polycystic ovary syndrome (PCOS). METHODS: A secondary analysis of the data from 626 women with PCOS from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Network trial was performed. Women had been randomized to up to six cycles of clomiphene citrate alone, metformin alone, or clomiphene citrate plus metformin. Women were assessed for occurrence of ovulation, conception, and live birth in relation to prior bleeding episodes (after either ovulation or exogenous progestin-induced withdrawal bleed). RESULTS: Although ovulation rates were higher in cycles preceded by spontaneous endometrial shedding than after anovulatory cycles (with or without prior progestin withdrawal), both conception and live birth rates were significantly higher after anovulatory cycles without progestin-induced withdrawal bleeding (live births per cycle: spontaneous menses 2.2%; anovulatory with progestin withdrawal 1.6%; anovulatory without progestin withdrawal 5.3%; P<.001). The difference was more marked when rate was calculated per ovulation (live births per ovulation: spontaneous menses 3.0%; anovulatory withprogestin withdrawal 5.4%; anovulatory without progestin withdrawal 19.7%; P<.001). CONCLUSION: Conception and live birth rates are lower in women with PCOS after a spontaneous menses or progestin-induced withdrawal bleeding as compared with anovulatory cycles without progestin withdrawal. The common clinical practice of inducing endometrial shedding with progestin before ovarian stimulation may have an adverse effect on rates of conception and live birth in anovulatory women with PCOS.
Int J Clin Exp Pathol. 2013 May 15;6(6):1157-63. Print 2013. Does progesterone-induced endometrial withdrawal bleed before ovulation induction have negative effects on IUI outcomes in patients with polycystic ovary syndrome? Dong X, Zheng Y, Liao X, Xiong T, Zhang H. PMID: 23696936
...The present study was performed to investigate whether progesterone-induced endometrial bleed before ovulation induction affects pregnancy in patients with PCOS who underwent intrauterine insemination (IUI) treatment. A total of 241 IUI cycles were retrospectively analyzed. Patients enrolled in this study underwent ovulation induction with IUI treatment from Jan. 2011 to Dec. 2012. The study group consisted of 184 cycles with progesterone-withdrawal bleed before ovulation induction. The control group included 57 cycles with spontaneous menses. The clinical characteristics, ovulation induction parameters and IUI outcomes, such as pregnancy rate and live birth/ongoing pregnancy rate, were compared between the two groups...In conclusion, our study showed that progesterone exerted a negative effect on endometrial development, which seemed to be associated with reduced pregnancy results in ovulation induction with IUI cycles.
 Prometrium Studies

Fertil Steril. 1991 Dec;56(6):1040-7. Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea. Shangold MM, Tomai TP, Cook JD, Jacobs SL, Zinaman MJ, Chin SY, Simon JA. PMID: 1743319
OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double-blind... INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo...RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects...

Friday, November 29, 2013

Sixth Annual Turkey Awards: PCOS Isn't a Real Disease

It's that time again ─ time for The Well-Rounded Mama's Annual Turkey Awards. Our sixth annual Turkey Award, to be exact!

These are the awards I hand out for fat-phobic treatment of people of size from care providers, biased attitudes or studies from researchers, or highlighting troubling trends in the care of fat pregnant women these days.

In past years, we've talked about fat-phobic care providers, scare-mongering and shaming tactics, jumping to conclusions about risksscorched earth tactics, and prenatal weight gain extremism,

This year I have spent quite a few posts focusing on treatments for PolyCystic Ovarian Syndrome (PCOS), and so this year I thought it fitting that the Turkey Awards also focus on PCOS.

PCOS: Real, or Just Another Excuse for Being Fat?

Despite all the research on PCOS, it's shocking that there are still care providers and others who don't believe that PCOS is a "real" diagnosis ─ that's it's just another ploy by obese people to make excuses for being fat. For example:
  • There's this entry over at "First Do No Harm," where the doctor tells a woman recently diagnosed with PCOS (by another doctor) that “PCOS isn’t a real disease, it’s been made up by fat women”
  • Or the spokesperson for a major medical organization who said, "The prevalence of PCOS appears to be rising because of the current epidemic of obesity"
Look, care providers. I get that you look at most women with PCOS and see lots of obesity. Yup, there's a strong correlation between obesity and PCOS. But not all fat women have PCOS. And some thin women have PCOS. It is doubtful that there is a one-to-one causal association here.

PCOS goes far beyond questions of fatness. It is an underlying metabolic and hormonal disorder that wreaks havoc in the body. It is indeed a REAL condition and it's NOT just a side effect of being fat.

If anything, PCOS probably predisposes to weight gain. That's likely why so many women with PCOS are fat.

But it doesn't mean that being fat causes PCOS.

Nor does it mean that if you just lose a bunch of weight, all symptoms of PCOS will disappear forever. Some people find that it helps, but many people don't.

And it certainly doesn't mean that fat people have invented a bogus disease to make excuses for their fatness or to cover up bad habits that they are just too lazy or stupid to resolve.

PCOS Denial

Why do some care providers refuse to believe that PCOS is real? I keep scratching my head over that one and this is what I come up with.

Some have simply been trained by medical schools to blame every health problem fat people have purely on being fat. Many won't believe anything that fat people say about their habits because they were taught that we are all in denial or lying about our habits.

Some like making assumptions about what fat people "must" eat so they can feel morally smug and superior. After all, their bodies work just fine and stay skinny with moderate habits. If ours are larger, it must be because of excessive habits, not some underlying metabolic difference. All bodies always work exactly alike, right?

Many want an easy answer for the tough symptoms of PCOS, a quick fix without acknowledging the complexity of the condition and its resistance to conventional treatment. Blaming fatness and promoting weight loss as the cure gives a conveniently easy answer without having to look deeper at the fact that many people don't experience a magical cure with weight loss and that most weight loss rebounds with enough time.

Some truly mean well but feel powerless when dealing with PCOS. People don't like to feel powerless, so when they can't provide a quick fix, they often dismiss or minimize symptoms, attribute it to something else, or blame something about us for developing symptoms at all.

Because, you see, if you can blame the victim for their disease, then you don't have to feel bad when you can't instantly cure someone. And then you don't have to admit that body differences go far deeper than we want to acknowledge. Or believe inconvenient truths, like not all bodies are created with a level playing field.

If providers can believe it's our fault, then it conveniently frees them from even needing to TRY to figure it out or cure it. Just blame the victim and their "lack of willingness to change" and move on. Problem solved. No need to agonize over it or feel bad or to admit that you are powerless to fix some things.

Fortunately, awareness has been raised in recent years and most providers these days don't treat PCOS like a figment of the imagination. They know it's a real condition and they truly care about helping us maximize our health and find some answers. There are still some turkeys out there who don't get it, but thankfully, most do.

But even among those who recognize PCOS as a real condition, there are still plenty who think that weight loss is a sure cure for it and that anyone still suffering from symptoms just hasn't tried hard enough (or used the "right" program) to lose the weight.

Despite all the progress we've made on PCOS, it still all comes down to a focus on weight for far too many providers. 

What Women With PCOS Want From a Provider

Women with PCOS want a provider who understands that there IS a real condition called PCOS, and that it's not just tied to "bad" habits or being fat.

We want a provider who gets that there is something different about our underlying metabolism and/or hormones, and that THIS is the primary source of our symptoms, not fatness.

We want a provider who doesn't think we are looking for an excuse for being fat, who will take our symptoms seriously, and who will work with us to find the best treatment plan for our individual circumstances and desires.

We want a provider who understands that while healthy nutritional habits and regular exercise can go a long way towards helping lessen PCOS symptoms, they don't cure anything ─ and often provide only a temporary reprieve. They sure as heck don't make most of us permanently skinny. We want providers who understand that it's far more complex than that.

We want providers who won't just make assumptions about our habits based only on our weight. We want providers who will encourage us to work on healthy habits, but without necessarily focusing on the scale as the main measure of healthy habits. We want providers who understand that healthy habits can still exist in the context of a high BMI and independent of actual weight loss.

Some women with PCOS will be interested in weight loss and some will not. We want providers who are respectful of either choice but who understand that all our issues won't be solved just by losing weight or trying diet "x." If we decide not to pursue weight loss, we want providers who will respect our right to patient autonomy and who will be willing to focus on other modalities of treatment.

Final Thoughts

Providers, believe that PCOS is a REAL condition ─ one that is not created by carelessness, willfulness, ignorance, or bad habits ─ even though we don't fully understand exactly what it is yet or how to fix it.

Stop making weight the center of your focus around PCOS. It is just one facet of this condition. You can discuss weight loss as one of the choices on the spectrum of care, but realize how difficult it is and how the metabolic differences of PCOS works against its success. Don't make weight loss the only tool in your PCOS toolbox, don't harass us about it, and respect our choice if we decide against focusing on it.

Stop blaming the victim, and realize that PCOS is a complex condition that goes beyond simple fixes. Help us experiment to find the treatment modality that fits our circumstances and desires, rather than working from some inflexible formula of what all PCOS patients "should" do.

Work WITH us instead of lecturing AT us. Treat us with dignity and respect, listen to us, and individualize our care according to our wants and needs. Then ─ and only then ─ will we make true progress towards optimal health with PCOS.

*Have you encountered weight bias when trying to get diagnosed with PCOS? Did your providers blame all your symptoms on fatness instead of exploring the possibility of PCOS or other issues? Do your providers remain fixated on weight loss as a "cure" for PCOS to the exclusion of other possible treatments?  What would you like to tell providers about serving women who might have PCOS? Share your stories in the comments section.

Tuesday, November 19, 2013

Your Weight Alone Means You Are Probably Going to Have a Cesarean

Another iconic entry from My OB Said What!?!:
“You are grossly overweight. I need you to realize that your weight alone means you are probably going to have a cesarean section. Your previous weights in other pregnancies are irrelevant.”  
- OB to mother with two previous uneventful vaginal deliveries and currently now 32 weeks pregnant with her third
This is such a frustrating entry. It's a classic case of fat bias predisposing towards cesarean delivery.

In multips, prior vaginal births are highly predictive of further vaginal births. Not that a woman can't have vaginal births and then have a cesarean, of course; fetal distress happens, poorly positioned babies happen, unforeseen medical circumstances may necessitate a cesarean, etc.

But generally speaking, one of the best predictors for vaginal birth is a previous vaginal birth.

Yet apparently not for fat women. Certainly not with this doctor.

This woman had not just one but TWO prior vaginal births (so obviously it wasn't just a fluke or random luck), but none of that mattered to the OB, who had the preconceived notion that a high weight almost certainly means a cesarean section and that's that.

And the sad thing is, for many care providers, expectations become a self-fulfilling prophecy.

Whatever happened to a caregiver expecting normalcy?

Although it is prudent to be aware of possible complications with women of size, the best course is to expect normalcy in fat women, too.

Yet the extreme perception of danger around obese pregnancy means that many care providers expect "abnormalcy" in this group, in virtually every case, even when multiple prior pregnancies have been healthy and normal in every way.

Sadly, people generally find what they want to find...or create it.

Wednesday, November 13, 2013

PCOS and Diabetes: Glucose-Lowering Medication Options

We've been discussing Polycystic Ovarian Syndrome (PCOS) and its impact on the health of women of size. Today, let's discuss the use of glucose-lowering medication options for those who have developed diabetes.

So far we've talked about PCOS's definition and symptoms, how it presents, its testing and diagnosis, and its possible causes. Now we are discussing common treatment protocols for PCOS, and the pros and cons of each.

We've already discussed insulin-sensitizing medications like metformin, the TZDs, and inositol.

Now let's chat about medication options for lowering blood sugar for those women with PCOS who have already developed diabetes. These drugs are not to treat PCOS per se, but to treat diabetes, which many women with PCOS develop at some point as they age.
Disclaimer: I am not a medical health-care professional. While the following information is based on my best understanding of the research, always do your own research. This information is not a complete explanation of all the risks and benefits of a particular medication, nor is it medical advice about a health condition or treatment. Consult your healthcare provider before making any decisions about your care plan.
Trigger Warning: Passing mention of the possible weight effects of several medications, and a mention of the emphasis on weight loss in typical diabetes treatment.

How different blood sugar medications affect the body
It is an unfortunate truth that many women with PCOS will probably develop full-blown diabetes at some point in their lives. As a result, women with PCOS often need to inform themselves about diabetes medication choices. This post is designed to help with that process.

For a long time, doctors had few choices for medicines to treat Type 2 diabetes. In the past 20 years, however, their choices have greatly expanded. Now there are so many choices, it's hard to know which is the best choice for any one person. Negotiating this maze can be confusing for care providers, let alone consumers.

But basically, diabetes medications attempt to address the two main problems of type 2 diabetes:
  1. Insulin Resistance, which makes it hard for the body to utilize its own insulin optimally
  2. Pancreatic Beta Cell Defects, which makes it hard for the body to produce enough insulin for its needs
Most diabetes medications reduce blood sugar by either reducing insulin resistance, stimulating the body's own insulin secretion, or by delaying carbohydrate absorption.

Remember, diabetes is usually a progressive condition. What works at first to control blood sugar will gradually become less effective. Treatment must change over time to reflect the needs of the patient.

Lifestyle changes can be helpful for some at first, but eventually most diabetics need medication. This post will discuss diabetes drug options, including some of the newer medications. However, it is not meant to be a complete discussion of these options; rather, it is an introduction to some of the more common options out there.

The most common medications used to control high blood sugar include:
  • Insulin Sensitizers - medications to lessen insulin resistance 
  • Secretagogues - medications to force the pancreas to secrete more insulin 
  • Alpha-Glucosidase Inhibitors - medications to delay carbohydrate digestion
  • Incretin Mimetics - synthetic gut hormones to increase insulin production, but only in response to high blood sugar (technically also a secretagogue, but by a different means)
There are other drugs that control blood sugar in other ways, but they are less common and will not be covered in this post.

Because each person has unique needs, conditions, and reactions to medications, it's very important to consult closely with your care provider when developing your care plan.

If you find your care provider is not listening to you or treats you poorly because of your size or PCOS status, then vote with your feet and find a new care provider. The last thing you should do is go without care or put up with suboptimal care.

Managing diabetes is not an easy task, but it is critical to your long-term health. Therefore it's important that you have a care provider you can trust, who truly has your best interests at heart, and who listens to your input. Keep searching till you find one of these.

Insulin Sensitizers

Over time, many people become resistant to their own insulin, causing the body to try to crank out more and more insulin to compensate. Eventually, the pancreas can no longer produce enough of its own insulin to keep blood sugar normal. Blood sugar rises and complications start to develop.

Rather than keep on adding more insulin to the mix, one of the most logical diabetes treatments is to encourage the body to use its own insulin more efficiently.

Exercise is one of the best ways to improve insulin sensitivity, so regular exercise (both aerobic and weight training) is one of the rock-solid pillars of diabetes treatment. Research shows that exercise alone can lower blood sugar significantly, sometimes by 0.5 - 1% of the HbA1c reading. This is as good as some diabetes medications.

However, as diabetes progresses, exercise alone may not be enough. Insulin-sensitizing medications can help. It used to be that these were only prescribed once a trial of diet and exercise had failed to keep blood sugar normal. Now, however, the standard of care is to start an insulin-sensitizing medication along with diet and exercise as soon as diabetes is diagnosed. Outcomes seem to be better by starting multiple modes of care at once.

[Note ─ "diet" in this context does not have to mean a low-calorie or reducing diet, but rather a way of managing food intake that keeps the blood sugar as normal and as stable as possible. This has more to do with timing, choice, and combination of foods than anything else.]

Of course, Insulin Resistance (IR) is not just a problem of diabetes; it is also one of the primary problems in PCOS. Most women with PCOS have hyperinsulinemia (too much insulin), probably caused by problems with insulin signaling pathways or insulin receptor defects. The theory is that by encouraging the body to use its own insulin better, some of the hormonal imbalances of PCOS may be lessened.

As a result, insulin-sensitizing drugs are a cornerstone of therapy for both women with PCOS and Type 2 Diabetics.

As we've mentioned before, there are two main drug classes used to improve insulin sensitivity, the biguanides and the thiazolidinediones (also known as glitazones or TZDs).

The primary insulin-sensitivity drugs on the market today are the biguanide Glucophage (metformin) and two TZDs, Avandia (rosiglitazone) and Actos (pioglitazone). Because these drug classes have been extensively discussed in previous posts, they will only be briefly summarized here.

Metformin is the first-line treatment of choice in diabetes. It works primarily by decreasing glucose output by the liver, but also improves insulin sensitivity elsewhere in the body.

Its long record of safety and efficacy makes metformin an excellent choice for most diabetics, despite the G.I. side effects that some people experience. It is inexpensive and extremely effective, lowering A1c blood sugar on by about 1-2% on average. It has been shown to improve not only clinical risk factors, but also long-term outcomes (endpoints like cardiovascular events and death). This is a huge advantage that no other diabetes drug can claim at this time.

Because of its effectiveness against insulin resistance, many care providers also prescribe metformin for women with PCOS. Although not every care provider agrees, many care providers see metformin as the drug of choice for PCOS, regardless of glucose status. Certainly, in pre-diabetic and diabetic women with PCOS, it is the first drug that should be tried.

Another effective insulin-sensitizer is the family of TZDs (glitzaones). TZDs also are extremely effective at reducing blood sugar, also around 1-2% A1c on average, and improve symptoms of PCOS. They often work in people who are resistant to metformin.

TZDs improve glucose uptake and insulin sensitivity in muscle and fat tissue in the body. They work by stimulating peroxisome proliferator-activated receptors (PPARs); most of the current generation of TZDs stimulate the PPAR-gamma receptor. Future generations of TZDs may stimulate other PPAR receptors (or multiple receptors).

Unfortunately, the current generation of TZDs have been associated with increased cardiovascular risk or liver toxicity; Rezulin (troglitazone) was pulled from the market, and Avandia (rosiglitazone) has been restricted in some countries. On the other hand, Actos (pioglitazone) so far seems to have fewer side effects and is still in regular use.

In addition to metformin and the TZDs, an emerging class of insulin-sensitizers are the inositols (myo-inositold-chiro inositol). Inositols work by improving insulin signaling, which helps the body use its own insulin more effectively. They seem particularly effective for women with PCOS. They received a lot of buzz at first and are now experiencing a resurgence of interest, but research is still emerging on their safety and efficacy.

Metformin, TZDs, and inositols are all used in women with PCOS, although their use in those who still have normal blood sugar is controversial. Some care providers feel they should be reserved only for those who have developed diabetes, while others feel that they should be utilized long before diabetes develops in order to help prevent or delay it, as well as to minimize symptoms of PCOS.

Regardless, insulin sensitizers are one of the most important medications for both PCOS and diabetes, because they help the body use its own insulin more efficiently. This is the first and most important goal for clinicians to address.

Insulin Secretagogues: Increasing Insulin Production

There are several classes of drugs commonly used to lower blood sugar in diabetics. One of the oldest is the secretagogues, including sulfonylureas and meglitinides. These work in a different way than the insulin-sensitizing drugs.

Remember, in Type 2 diabetes, the problem is usually both insulin resistance and a relative shortfall of insulin relative to the body's needs. It's not just the body's resistance to its own insulin, but also that the pancreas cannot produce enough to compensate, either because of an inborn beta cell defect or because the pancreas has exhausted itself.

The secretagogues work on this problem by forcing the pancreas to produce more insulin, which in turn, helps to lower blood sugar. If there is enough pancreatic beta cell reserve, these drugs can work quite well. If there is not enough pancreatic beta cell reserve, however, these medicines don't work very well.

Use of secretagogues is controversial in women with PCOS. These drugs do not reduce the hyperinsulinemia of PCOS and may actually worsen outcomes because they force the pancreas to produce more insulin. However, because high blood sugar causes so much damage in the body, they are often still used with diabetics (PCOS or not) if normal blood sugar cannot be achieved on metformin or a TZD alone.

Sulfonylureas are the most common secretagogue and were the first widely-used oral anti-diabetes medication. Modern versions include drugs like glimepiride, gliclazide, glibenclamide (glyburide), and glipizide. An older version that is still sometimes used is tolbutamide.

The advantages of sulfonylureas are that they are extremely effective at lowering blood sugar and are available in generic forms so they are very affordable. They work quickly, are taken orally, and are easy to dose.

The side effects of sulfonylureas nearly always include some weight gain and periodic episodes of low blood sugar (hypoglycemia) as a result of the increased insulin. Hypoglycemic episodes can be dangerous, so this is a serious side effect that must be watched for carefully. A regular meal schedule is important, and meals should not be delayed or skipped.

Sulfonylureas are often quite effective at lowering blood sugar at first but lose their efficacy over time as the pancreas exhausts itself from producing more and more insulin. They may also increase the risk of poor long-term outcomes like cardiovascular disease and cancer-related mortality compared to treatment with metformin. This is a serious disadvantage, but the risk may vary strongly by which sulfonylurea is used.

Meglitinides are another medication that make the pancreas produce more insulin. These drugs include repaglinide (Prandin) and nateglinide (Starlix). They are similar to sulfonylureas but work on a different binding site in the pancreatic beta cells. They also differ in how they are excreted and how long their effects last.

Meglitinides have side effects similar to the sulfonylureas, including weight gain and low blood sugar episodes. However, the side effects are usually less severe than with the sulfonylureas. They are taken shortly before meals, have a quick effect on insulin production, and are particularly helpful in lowering postprandial blood sugar (the rise in blood sugar after eating). This can be a key advantage for people who have normal fastings but significantly raised postprandial readings.

Repaglinide has been shown to be effective in lowering blood sugar, even in elderly patients and in those with kidney disease. It is usually used in combination with metformin and has been shown to be more effective than metformin alone. However, its disadvantage is that it is expensive and can result in low blood sugar episodes.

Obviously, medications that increase insulin production are not ideal for most women with PCOS, since they already produce far too much insulin. These medications can temporarily improve blood sugar but may worsen PCOS symptoms. This is why the first-choice drugs for diabetic women with PCOS are usually insulin-sensitizers.

However, sulfonylureas and meglitinides are very effective at lowering blood sugar long-term, and are usually fairly well tolerated. Thus, they are often part of diabetes treatment, even in women with PCOS, because as diabetes progresses, keeping blood sugars as normal as possible will hopefully help prevent the most serious complications of diabetes, like heart disease, stroke, neuropathy, or eye damage. This may be worth the trade-off of possibly worsening PCOS symptoms.

Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors are another medication option for diabetics.

This group includes acarbose (Precose) and miglitol (Glyset). These are oral medications and should be taken with the first bite of each meal. They inhibit the production of alpha-glucosidase enzymes, which are intestinal enzymes needed to digest carbohydrates.

These medications act by delaying carbohydrate absorption, which can help lower blood sugar. They also lower insulin levels somewhat. They primarily affect post-meal blood sugar levels because they inhibit the enzymes close to the stomach and delay carbohydrate digestion to lower in the intestines. Blood sugar will still go up, but much more slowly and evenly, which will also help blunt the insulin surge the body produces in response to a quick rise in blood sugar.

However, these medications don't lower blood sugar all that much. Some sources state that they lower the HbA1c only by 0.5 - 0.8%. They have little effect on lipids or bodyweight. The effect, if any, on mortality or cardiovascular events is unclear.

The good news is that this medication does not increase insulin secretion in the pancreas, so it should not add to hyperinsulinemia problems in women with PCOS. Because it doesn't increase insulin production, it doesn't usually cause low blood sugar episodes or weight gain unless combined with a sulfonylurea or meglitinide. Another advantage is that acarbose has been on the market since 1995 and an affordable generic form is available.

The bad news is that because it delays carbohydrate absorption, it has lots of G.I. side effects, including diarrhea and gas/bloating. In one study, as many as 50% of people who took these medications experienced significant G.I. symptoms, although this number decreased to 14% over time.

More is not better; high doses result in more G.I. side effects without an increase in efficacy. If you are prescribed acarbose, slowly increasing the medication dosage over time and reducing the amount of carbohydrate in a meal may help reduce G.I. side effects.

Because of the G.I. side effects, it should not be prescribed to people with Inflammatory Bowel Disease or Crohn's Disease. Hepatitis may also occur, so liver enzymes must be monitored while on this drug.

Because it offers only mild advantages in exchange for significant side effects, this medication is not used as much as other diabetes medications, but it can be used in combination with them to improve blood sugar via multiple pathways.

It seems most useful for those who are recently diagnosed with diabetes and those who have normal fasting blood sugars and only mildly-elevated post-meal readings.

Incretin Mimetics

Image from Gallwitz 2010
A fairly new but much-heralded class of anti-diabetes drugs includes the incretin mimetics.

Incretins are G.I. hormones like glucagon-like peptide (GLP-1) that are produced by your own body. They help your body respond to glucose production from food. They are responsible for much of your insulin response to food intake.

Incretin mimetics are a man-made version of these G.I. hormones, synthesized from other substances. They are designed to work like your body's own incretins, but to have a longer-lasting effect.

Technically, incretin mimetics are also a secretagogue because they help the body produce more insulin, but are generally discussed separately from sulfonylureas and meglitinides because they act only in response to raised blood sugar. 

Once your blood sugar is normal, the action of incretin mimetics shuts off, making low blood sugar episodes less likely. Sulfonylureas, on the other hand, cause your pancreas to keep churning out insulin no matter what your blood sugar is doing, making low blood sugar episodes more likely. This is a very important distinction.

Your own gut incretins work by causing your pancreatic beta cells to release more insulin, by inhibiting glucagon release from pancreatic alpha cells (thereby keeping your liver from dumping its stored glucose into your body), and by slowing absorption of nutrients into the blood stream by reducing gastric emptying.

Incretins also increase pancreatic beta cell proliferation, lessen beta cell death, and improve first-phase insulin release. 

In other words, they help the pancreas work more quickly and efficiently, and they help preserve pancreatic function longer. This is a huge benefit. They are the only medication that is thought to help keep or even improve beta cell function, which may delay or keep diabetes from progressing so quickly.

The problem with your own body's incretins is that their effect doesn't last long; they work for just a few minutes and then they are blocked by DPP-4 enzymes. So for a long time, incretins really weren't that useful for helping to control blood sugar in diabetics; you'd have to receive a continuous infusion for them to help.

But now there are incretin mimetics, synthesized from other sources, that are similar to your own incretins but changed just enough to be effective. They are called "mimetics" because they mimic the action of your own G.I. incretin hormones, but are not quite the same because they make the effect last longer. Incretin mimetics include:
  • GLP-1 receptor agonists
  • GLP-1 analogs
  • DPP-4 inhibitors
GLP-1 Receptor Agonists are the most common form of incretin mimetics. They are a protein, so if they were taken orally, they would be digested. Therefore, they must be injected in order to be effective.

Byetta (exenatide) is a synthetic version of a substance found in the saliva of Gila monster lizards. It is a GLP-1 receptor agonist that is just different enough from your own body's GLP-1 that it is absorbed more slowly. It can lower A1c numbers by up to 1.5%, which is quite significant.

Byetta must be injected twice a day, preferably an hour before breakfast and dinner. It slows down the progression of food or medicines through the intestinal tract, so any oral medications should be taken an hour before Byetta is injected.

Like insulin, it should be kept out of hot temperatures and direct sunlight. The manufacturer recommends refrigerating it until it is first opened, then storing it in a cool area for up to 30 days.

Byetta's G.I. side effects include nausea, vomiting, and diarrhea. Many people report a feeling of fullness, stomach discomfort, and nausea when first starting the drug. These effects are reduced after a few weeks, but may recur periodically.

Byetta is excreted via the kidneys and so should not be used in people with severe kidney disease. It can sometimes cause headaches, sweating, acid reflux, or thyroid issues. It has been under close scrutiny for a possible increase in pancreatitis, and should not be prescribed to anyone with a history of pancreatic issues, alcohol abuse, or a family history of thyroid cancer.

Doctors like Byetta because it often results in a small weight loss (about 2-10 lbs.), and can be used in conjunction with metformin, TZDs, or sulfonylureas. The main disadvantage to Byetta is that it must be injected, and multiple times per day at that.

The drug companies have responded to this concern by creating a long-acting version (Bydureon); patients only have to inject it once a week instead of twice a day. So far, the long-acting version seems to improve blood sugar better and reduce some G.I. issues, but longer trials are needed.

Victoza (liraglutide) is a GLP-1 analog. It is structurally very close to the GLP-1 hormone that naturally occurs in the human body.

Its main advantages are that it only has to be injected once per day, without regard to time of day or mealtimes, and it has a low rate of low blood sugar episodes. It also improves triglyceride levels better than Byetta, although whether this has any long-term effect on cardiovascular events is unknown.

Its main side effect is mild nausea. Some studies suggest it may lower blood sugar even more than Byetta. It has also been shown to lower blood pressure and sometimes result in a small amount of weight loss. However, it is a newer drug (FDA-approved in 2010) and only time will tell how safe it is.

So far, the GLP-1 drugs do not seem to increase cardiovascular risk in the short term (and may help decrease blood pressure and cholesterol), but more research is needed to confirm this and to investigate its long-term effects.

Like Byetta, Victoza should not be prescribed to people with a history of pancreatitis or thyroid cancer. Caution should also be taken in people with a history of gallstones.

DPP-4 inhibitors act by inhibiting the enzyme that inactivates the body's own GLP-1, thus increasing your own GLP-1's length of effect in the body.

Januvia (sitagliptin) is the most famous of the DPP-4 inhibitors, although there are others as well (saxagliptin/Onglyza, vildagliptin/Galvus, and linagliptin/Tradjenta). Januvia was approved by the FDA in 2006.

The main advantage of DPP-4 inhibitors is that they can be taken orally, as opposed to the GLP-1 drugs which must be injected. DPP-4 inhibitors also result in less nausea and so are better tolerated by many patients.

However, they do not decrease blood sugar as well as GLP-1 drugs, and they are usually weight neutral (no gain but also no loss, which of course most doctors see as a disadvantage). Other side effects include an increased reporting of respiratory infections and cold-like symptoms with nearly all the DPP-4 inhibitors. Headaches may also be increased.

On the other hand, when combined with metformin, DPP-4 inhibitors improved post-meal blood sugars far better than metformin alone, which also improves long-term blood sugars (A1c) more efficiently.

One of the most exciting potential effects of DPP-4 inhibitors is that they are thought to preserve or even improve pancreatic function, thus maintaining the patient's own insulin function over time. Since the progression of diabetes involves declining pancreatic function, DPP-4 inhibitors are sometimes prescribed early on in the treatment of diabetes, either as a stand-alone therapy or in combination with metformin or TZDs, in order to delay the progression of diabetes and give the patient more time before drugs with more serious side effects are needed.

recent drug trial found that DPP-4 inhibitors did not increase the risks of heart attack, pancreatic inflammation or cancer, but may modestly increase the risk for heart failure. They should not be prescribed in conjunction with sulfonylureas but, as noted, may be prescribed with metformin or the TZDs.

All in all, the incretin mimetics seem to be a major advance in treating diabetes, especially when other treatment options (like metformin) aren't enough. They effectively lower blood sugar, and have modest beneficial effects on blood pressure, insulin sensitivity, cardiovascular risks, and other clinical goals. Many clinical guidelines now promote early use of incretin mimetics, rather than waiting until the diabetes has progressed.

However, they are a relatively young drug class, so more research is needed. They may raise the risk for thyroid cancer, for example. Since each drug presents its own unique profile of benefits and risks, careful clinical judgment is needed to individualize their usage appropriately.

The other major disadvantage of the incretin mimetics is that they are very expensive (several hundred dollars a month, usually), and many insurance plans do not cover them.

Combination Drugs

Image from Medscape (link in references)
Diabetes treatment these days often combines two or more drugs together. Rather than using an ever-increasing dose of one drug, care providers often prescribe two drugs instead to work on blood sugar in different ways and therefore lower blood sugar more effectively.

This combination therapy offers a distinct advantage in that it targets not only insulin resistance, but also pancreatic beta cell function and hepatic (liver) glucose production.

Combination therapy often has better results than monotherapy. Research shows that more patients reach blood sugar target ranges when two drugs are used than when one drug is used at a higher dose.

Combining two medications into one pill also makes it simpler and more convenient for the consumer, making them more willing to take the drugs as needed. Furthermore, the drug company is able to hold onto exclusive patent use longer for the drugs, thus prolonging their profit margins.

Time will tell if these combination therapies truly improve long-term outcomes better than monotherapy, but so far results seem promising. Here are some common combination drugs:
  • Metaglip is a combination of metformin and the sulfonylurea glipizide (a generic form is available)
  • Glucovance is a combination of metformin and the sulfonylurea glyburide (a generic form is available)
  • Janumet is a combination of metformin and the DPP-4 inhibitor sitagliptin/Januvia
The Importance of Reducing Stigma

The bottom line is that women with PCOS are profoundly vulnerable to developing Type 2 diabetes at some point in their lives and thus need good information about the latest diabetes drug choices.

It should be pointed out that this tendency towards diabetes does not reflect a lack of willpower or a poor lifestyle, but rather the underlying metabolic issues of PCOS. This cannot be emphasized enough.

In our society, there is far too much shaming and blaming around the development of Type 2 Diabetes. This leads many people to put off or avoid medical treatment until their blood sugar is very high or they have developed significant complications.

It also blames people for developing something that may have far more to do with an inborn metabolic defect than with their habits. Although poor habits can impact health and personal responsibility is important, there are many people with very poor habits who never develop diabetes, and some people with very reasonable habits who do develop diabetes. It's rarely related to only lifestyle, but more to a combination of factors, some of which are modifiable and some of which are not.

In the case of PCOS, there is almost certainly some sort of underlying metabolic defect that predisposes these patients to diabetes. Combine that with low pancreatic beta cell reserve, and you get early-onset diabetes that has nothing to do with habits or personal responsibility.

Careful attention to nutrition and exercise and use of some medications may help prevent or delay some cases but many women with PCOS will develop diabetes despite their best efforts. Therefore it's important to reduce the stigma of this diagnosis so it can be diagnosed quickly and treated effectively.

Finding diabetes early on can help delay the progression of diabetes, and may even prevent some of the more serious complications. It's important that women with PCOS feel comfortable in getting yearly blood sugar tests to make sure any problems are caught quickly, and that those who do develop diabetes get treatment that does not shame them or inhibit their willingness to pursue treatment. Yet far too many receive scoldings and blame and reluctance to prescribe any help except dieting.

The scoldings, shaming, and emphasis on weight loss at any cost causes many fat people to avoid or delay seeing a doctor. It should be pointed out that although weight loss is sometimes helpful to blood sugar in the short term, it often leads to regain and a higher weight than the patient began with. In addition, recent research suggests that it does not decrease cardiovascular events.

Care providers need to take a more nuanced view of weight loss as the foundation of diabetes prevention and treatment. While some patients will want to pursue weight loss, others will not because they do not want to risk rebound weight cycling or because they are concerned about developing disordered eating patterns. Opting out of weight loss treatment can be a legitimate choice and should be respected by care providers.

It's important for patients to know that lifestyle tweaks (like increasing exercise or lowering carbohydrate intake) can often improve blood sugar and other risk factors significantlyindependent of weight loss. Lifestyle tweaks do not have to involve weight loss to be effective. Care providers need to incorporate more Health At Every Size models that emphasize healthy habits and improving lab numbers instead of focusing only on the scale.

The current stigma around the diagnosis and treatment of Type 2 diabetes just adds to the disease burden felt by people with diabetes and PCOS, and may well backfire in trying to improve outcomes in this group.*

Summary of Diabetes Medication Options
Image from Medscape and Joslin Diabetes Center

The good news is that people with diabetes are living longer and with a better quality of life now, thanks to easier self-monitoring and better medication options.

However, it is very difficult to find the "perfect" diabetes drug because there are so many competing priorities. You need a drug that:
  • reduces insulin resistance
  • improves pancreatic beta cell function
  • reduces blood sugar, both fasting and after meals
  • reduces the average blood sugar over time (A1c)
  • does not cause low blood sugar episodes
  • does not have side effects (or only mild side effects)
  • does not cause weight gain
  • delays the progression of diabetes
  • is safe for people with kidney or liver impairment
  • does not have many drug interactions, especially with blood pressure or lipid drugs
  • is easy to take (preferably once daily)
  • is not too expensive
  • is covered by most insurance
Unfortunately, there is no drug that meets all of these criteria. All involve a trade-off of some sort. This is the challenge of treating diabetes, to find the "sweet spot" of treatment that involves the most benefits for the fewest risks.

What's most important is that blood sugar is lowered. That is the most important goal of diabetes treatment, and patients may have to accept some side effects or disadvantages in order to achieve this most basic goal. What side effects or trade-offs are acceptable, however, will differ from person to person.

Because of decreasing pancreatic function leads to diabetes progression, sooner or later nearly everyone with diabetes is going to need some sort of medication. 

Which drug is used will depend on how high your blood sugar is, what additional complications you may have developed, what other medications you may be on, the side effects you experience, and how you respond to the various options. An individualized treatment plan is important and will change over time in response to your condition.

The medication uniformly recommended as the first-line choice of therapy in diabetes is metformin. It is comparatively safe and well-tolerated, and is quite effective at lowering A1c levels. In addition, it works to increase insulin sensitivity, which in turn seems to improve long-term outcomes, including cardiovascular disease and death.

TZDs are another insulin-sensitizing medication which can be used in patients who do not tolerate metformin or who are metformin-resistant. Many people with severe diabetes are able to normalize their blood sugar with a combination of metformin and a TZD. However, TZDs come with significant risks, including edema, liver issues, and heart failure. They should only be used with caution.

The inositols are another option for lessening blood sugar and improving insulin sensitivity. D-chiro-inositol seems to be more effective for this than myo-inositol, and may be particularly effective for women with PCOS. However, studies so far are small and of uneven quality. It is also not clear how inositols may interact with other medications. Research is ongoing.

Secretagogues such as sulfonylureas and meglitinides can be used in addition to metformin or a TZD. They work by forcing the body to continually produce more insulin. They are extremely effective in lowering blood sugar in those people with significant pancreatic reserves. However, these drugs have substantial side effects, and they may increase the risk for cancer and cardiovascular issues. Because they increase insulin production and most women with PCOS already have too much insulin, their use in PCOS is more questionable but cannot be ruled out.

Alpha-glucosidase inhibitors like acarbose slow down digestion of carbohydrates enough to blunt post-meal blood sugars significantly. Although they do not lower blood sugar as much as some other medications, they can still be useful for some patients, especially early in the course of diabetes.

Incretin mimetics are a fairly new class of drugs and we are still learning about their risks and benefits. Thus far, they are a very promising addition to diabetes treatments but longer-term research is needed.

DPP-4 inhibitors are often prescribed to newly diagnosed diabetics nowadays because they are thought to preserve pancreatic function fairly effectively. However, they are not as effective at lowering blood sugar, so they are usually prescribed in conjunction with metformin or a TZD.

GLP-1 agonists and analogs are injectable medications that mimic your own body's GLP-1 proteins but their effect lasts longer. Like sulfonylureas, they increase insulin secretion, but unlike sulfonylureas, they shut off when normal blood sugar is reached, decreasing the risk for low blood sugar episodes. They are often utilized when other medications start being less effective.

These are the main types of glucose-lowering medications on the market today. There are other types of glucose-lowering drugs (for example, SGLT-2 inhibitors, dual PPAR agonists, amylin agonist analogs), but those are much less commonly used or are very new to the market. In most cases, the drugs discussed earlier are the main diabetes medications you will encounter right now.

However, there are sure to be new drugs in the future, so it's important to keep on top of the latest research. When considering a new drug, remember that medications are always a work in progress. Serious side effects may not become apparent until population-wide use, like with some of the TZDs. So while many of these newer medications have great advantages, long-term use may turn up problems currently unknown to us.

And of course, even the best medications always have pros and cons, risks and benefits. The complete profile must be considered when deciding on a treatment plan. Sometimes a known risk is worth taking if the advantages of the medication are strong enough, but this trade-off can only be judged on an individual basis.

Another important point is that people respond differently to drugs. One woman may do extremely well on metformin with minimal side effects, while another cannot tolerate the G.I. side effects. Another may need metformin plus additional drugs in order to achieve normal blood sugar and reduce long-term complications. Still others may be able to achieve good results with only lifestyle, herbs, or alternative medicine options.

There is no one standardized treatment that is right for everyone. That's why it's so important to discuss the benefits and risks of all your treatment options with a trusted care provider. Do your research so you can become a partner in your own care.

Remember, a big limitation on our discussion here is that we do not have much information on the use of these drugs for women with PCOS. Most of the information we have on these drugs has been done on the type 2 diabetes population only, so their effect on diabetic women with PCOS is often speculative.

The bottom line is that data on the long-term efficacy and safety of these drugs in PCOS populations is urgently needed. 


*See the links in the post for many further references. Be aware that many of these references are very mainstream and so strongly promote weight loss as "the" treatment of choice.

Overview of Various Diabetes Medications

Oral Diabetes Medications for Adults With Type 2 Diabetes: An Update [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2011 Mar. Report No.: 11-EHC038-EF.
AHRQ Comparative Effectiveness Reviews.  PMID: 21735563
...The objective of this review was to summarize the benefits and harms of medications (metformin, second-generation sulfonylureas, thiazolidinediones, meglitinides, dipeptidyl peptidase-4 [DPP-4] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists), as monotherapy and in combination, for the treatment of adults with type 2 diabetes. RESULTS: The review included 140 randomized controlled trials and 26 observational studies..Most medications lowered HbA1c on average by 1 absolute percentage point, but metformin was more efficacious than the DPP-4 inhibitors. Two-drug combinations had similar HbA1c reduction. Compared with metformin, thiazolidinediones and sulfonylureas had a more unfavorable effect on weight (mean difference of +2.6 kg). Metformin decreased low density lipoprotein cholesterol relative to pioglitazone, sulfonylureas, and DPP-4 inhibitors. Sulfonylureas had a fourfold higher risk of mild/moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a fivefold increased risk compared with metformin plus thiazolidinediones. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas and bone fractures relative to metformin. Diarrhea occurred more often for metformin compared with thiazolidinedione users...Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports use of metformin as a first-line agent. Comparisons of two-drug combinations showed little to no difference in HbA1c reduction, but some combinations increased risk for hypoglycemia and other adverse events.
Links with Information on Various Diabetes Medications
Alpha-Glucosidase Inhibitors

Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003639. Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C. PMID: 15846673
BACKGROUND: Alpha-glucosidase inhibitors such as acarbose or miglitol, have the potential to improve glycemic control in type 2 diabetes mellitus. The true value of these agents, especially in relation to diabetes related mortality and morbidity, has never been investigated in a systematic literature review and meta-analysis...MAIN RESULTS: We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life...AUTHORS' CONCLUSIONS: It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated hemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.
Incretin Mimetics

Rev Diabet Stud. 2008 Summer;5(2):73-94. doi: 10.1900/RDS.2008.5.73. Epub 2008 Aug 10.
Targeting Incretins in Type 2 Diabetes: Role of GLP-1 Receptor Agonists and DPP-4 Inhibitors. Pratley RE, Gilbert M. PMID: 18795210
...Strategies to leverage the beneficial effects of GLP-1 include GLP-1 receptor agonists or analogs or dipeptidyl peptidase-4 (DPP-4) inhibitors-agents that act by slowing the inactivation of endogenous GLP-1 and GIP. The GLP-1 agonist exenatide has been shown to improve HbA1c and decrease body weight. However, exenatide is limited by its relatively short pharmacologic half-life, various gastrointestinal (GI) side effects, and the development of antibodies. Studies of a long-acting exenatide formulation suggest that it has improved efficacy and also promotes weight loss. Another prospect is liraglutide, a once-daily human GLP-1 analog. In phase 2 studies, liraglutide lowered HbA1c by up to 1.7% and weight by approximately 3 kg, with apparently fewer GI side effects than exenatide. DPP-4 inhibitors such as sitagliptin and vildagliptin result in clinically significant reductions in HbA1c, and are weight neutral with few GI side effects. This review will provide an overview of current and emerging agents that augment the incretin system with a focus on the role of GLP-1 receptor agonists and DPP-4 inhibitors.
Am J Manag Care. 2010 Aug;16(7 Suppl):S187-94. Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting. Garber AJ. PMID: 20809667
...The recently introduced incretin-based therapies serve to address some of the challenges associated with traditionally available oral antidiabetic agents. In addition to improving beta-cell function, stimulating insulin secretion, and inhibiting glucagon secretion, these agents reduce appetite, thereby stabilizing weight and/or promoting weight loss in patients with type 2 diabetes. Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these incretin-based therapies is recommended in the treatment of type 2 diabetes, based on their overall safety and ability to achieve the glycosylated hemoglobin level goal. As such, both the American Diabetes Association and the American Association of Clinical Endocrinologists/ American College of Endocrinology (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in both treatment-naive and previously treated patients. The AACE/ACE guidelines clearly state that these agents should not be limited to third- or fourth-line therapy.
Further studies/information on Incretin Mimetics:

*To the trolls: No, I do not have diabetes at this time. I write about this topic because I know that with PCOS, I am very likely to develop diabetes at some point. I also write about it because I have seen good friends treated so poorly by care providers that their diabetes went undiagnosed or under-treated for too long. I write about this because women need better and less-judgmental information in order to optimize their outcomes and quality of life.