Alert on Avandia!

altabes · 05-23-2007, 02:47 AM

A special report:

Avandia

As a result of recent news reports about the adverse cardiac problems linked to Avandia, the Project PCOS staff and board have put a section together to provide the community with news, information and views from our experts on this developing issue. Below you will find links to news articles and views from our experts. As always, if you have any questions about this or any other treatment for PCOS please contact your physician, healthcare provider, or general practitioner.
US Food and Drug Administration

Read the full alert from the United States Food and Drug Administration
Expert Articles

Coming Soon. responses from our experts, including Dr. Dennis Gage and Dr. Charles Glueck, who will review the data. We will post their reviews on our website and we will try to post the responses here, as well.

You can also view the Google news alerts about this topic by visiting the website

Kat, would love any additional info you have found on this issue!

All the Best,
Ashley

Jashobeam · 05-23-2007, 12:54 PM

My MIL has decided to stop taking Avandia after she heard the news yesterday. Her and FIL both were on it. I don't know if FIL is going to go off of it or switch to another med. One doctor site I looked at yesterday said the numbers looked off to him, and the risks were way overstated. I hope more research is done.

altabes · 05-23-2007, 01:41 PM

Definitely keep us posted, as this does affect more than just women with PCOS and would love to hear what docs are saying and feeling about this news release.

Thanks,
Ashley

artistic1 · 05-23-2007, 04:32 PM

is Avandia similar to Met?

Tracyarts · 05-23-2007, 11:46 PM

This report on Avandia really leaves me with a kind of sick feeling in the pit of my stomach as I had to discontinue taking it just last week because of dangerous complications involving severe edema/fluid retention, and suspected congestive heart failure.

CHF was ruled out and in less than a week off of Avandamet, I have seen a significant improvement with the edema and other problems I was having.

So this is definately something to look into further.
Tracy

altabes · 05-24-2007, 01:49 AM

AVANDIA is indicated as an adjunct to diet and exercise to improve glycemic control in patients. Most of the time it is not recommended as first-line treatment but, rather as an add-on,

It is also indicated for use in combination with metformin when diet, exercise, and both agents do not result in adequate glycemic control.

It has shown not to be as effective or safe as metformin in controlling the symptoms associated with IR and/or type II diabetes.

lilanika · 05-26-2007, 01:51 PM

Ashley,

What studies have shown that Avandia is less effective than metformin in controlling IR. I was always under the impression that is was the opposite.

altabes · 05-28-2007, 01:48 AM

Although Avandia has shown a slight advantage over metformin in some studies, due to the adverese side effects it is not a first choice and often the results of combining the medications as opposed to monotherapy have proven to be more effective in both the case of avandia and metformin in treatment. I will post a few studies for everyone to review as part of this thread.

Also, in most studies it shows Avandia is better at controlling blood glucose levels and not necessarily IR as a whole with lipids and other abnormalities.
Metformin seems to do a much better job at controlling the overall symptoms of PCOS and IR.

altabes · 05-28-2007, 01:57 AM

A
MERICAN
S
OCIETY FOR
R
EPRODUCTIVE
M
EDICINE
1209 MontgomeryHighway • Birmingham, Alabama 35216-2809 • T E L (205) 978-5000 • FAX (205) 978-5005 • E-MAIL a s r m @ a s r m . o rg • URLw w w. a s r m . o rg
PATIENT’S FACT SHEET
Insulin Sensitizing Agents and PCOS
Polycystic ovarian syndrome (PCOS) is a very common reproductive disorder. Women with PCOS frequently have irregular
menstrual cycles, excessive body hair, are overweight, and suffer from infertility. Many women with PCOS have a decreased
sensitivity to insulin for which their bodies compensate by overproducing insulin. The resulting high levels of insulin may
contribute to excessive production of androgens (male hormones, such as testosterone) and contribute to ovulation disorders.
In addition to reproductive problems, women with PCOS have a higher chance of developing medical problems such as Type
2 (non-insulin dependent) diabetes, high blood pressure, and heart disease. By the age of 40, up to 40% of PCOS patients
develop impaired glucose tolerance or clinical diabetes.
Given the strong evidence that excess insulin plays a role in the development of PCOS, it is reasonable to assume that reduc-
ing circulating levels of insulin may help restore normal reproductive function. This may be accomplished by weight loss,
improved nutrition, and exercise. These behavioral changes should be the first lines of therapy for an overweight woman with
PCOS.
Recently, new drugs approved by the FDA for the treatment of Type 2 diabetes have shown promise for PCOS. These drugs,
known as insulin sensitizing agents, have been shown to improve the body’s response to insulin, thereby reducing the need
for excess insulin and restoring the levels to normal. The best studied insulin sensitizing agent available in the United States
for women with PCOS is metformin (Glucophage
®
), a biguanide. Metformin reduces circulating insulin and androgen levels
and restores normal ovulation in some women with PCOS. Even if metformin alone does not restore ovulation, it may
improve a woman’s response to fertility drugs. Gastrointestinal irritation, especially diarrhea, is a common side effect. These
symptoms usually improve after a few weeks. Lactic acidosis is a rare but serious adverse effect of metformin. Metformin is
not recommended for patients with kidney, lung, liver, or heart disease.
Rosiglitazone (Avandia
™
) and pioglitazone (Actos
®
), which belong to the thiazolidinedione group of antidiabetic agents, are
also available in the United States for women with PCOS. Thiazolidinediones have been shown to reduce hyperandrogenism
and restore ovulation in some PCOS patients. Liver toxicity is the main concern with these agents. Liver tests should be per-
formed every two months for the first year and periodically thereafter. These medications should not be started in women with
any evidence of liver disease.
So far, the new insulin sensitizing agents have not been linked to birth defects in animals or humans, but they are not recom-
mended for use during pregnancy. Metformin should also be temporarily stopped prior to surgery or X-ray procedures that use
intravenous contrast.
Unlike ovulation induction drugs, insulin sensitizing agents have little or no risk of multiple pregnancies. More clinical studies
are needed to determine the outcomes, risks, and complications when these medications are used to treat PCOS. Although
results from clinical studies have been encouraging, the use of these medications in women with PCOS is still considered
investigational. In general, Metformin is used as the first insulin sensitizing agent; thiazolidinediones may be considered if
metformin is ineffective or not tolerated by the patient.
Present data suggest the use of insulin sensitizing agents for ovulation induction in PCOS patients who want to conceive.
Because these medicines correct the underlying metabolic abnormalities associated with PCOS, it is plausible that their long-
term use may delay the emergence or reduce the likelihood of developing Type 2 diabetes and cardiovascular disease. Since
data are lacking, h o w e v e r, long-term use of insulin sensitizing agents for this purpose cannot be recommended at present.
The American Society for Reproductive Medicine grants

altabes · 05-28-2007, 02:02 AM

Metformin (Glucophage®)?

Why has it become so popular?

Metformin was originally developed in 1957 and used worldwide before finally being introduced to the US in 1994. Metformin is approved by the FDA for treatment of type 2 diabetes. Metformin is a biguanide oral antihyperglycemic.

Metformin has many actions, the main being suppression of endogenous glucose production by the liver. Among oral antihyperglycemic medications it is unique, unlike the sulfonlyureas such as Diabinese® it does not cause hypoglycemia, weight gain, unfavorable alteration of lipids, nor increase insulin secretion.

Unlike thiazolidinediones such as Avandia® metformin does not cause weight gain, fluid retention, or potential idiosyncratic hepatotoxicity. Instead, metformin improves the effectiveness of insulin while maintaining or even decreasing insulin levels. Metformin decreases both basal and postprandial glucose levels, without the danger of hypoglycemia. Glucophage promotes weight loss and favorable changes in the lipid profile.

Metformin's effects are beneficial to women with type 2 diabetes. Metformin's unique properties have already established it as the initial medication of choice for type 2 diabetes treatment and produced many studies advocating other possible indications:

Metformin may decrease the progression from IGT to type 2 diabetes. In a prospective RCT, 3,234 women with IGT were followed for an average of 2.8 years. With placebo treatment, 11% per year progressed to type 2 diabetes. With a weight loss and exercise program, 4.8% per year progressed (a 58% improvement vs. placebo). With Glucophage treatment, 7.8% per year progressed (a 31% improvement vs. placebo). Weight loss and exercise remain the best hedge against developing IGT or type 2 diabetes. The usefulness of Metformin treatment in women simply with PCOS to prevent the development of IGT or type 2 diabetes is unknown. <LI class=textnormal>In women with PCOS, three randomized, placebo controlled trials found metformin plus Clomidto be more effective than Clomid alone in ovulation induction. Glucophage may also improve the quality of ovulation induced by recombinant FSH administration. Sustained metformin administration may establish regular menses in women with PCOS. <LI class=textnormal>Metformin may decrease the miscarriage risk associated with PCOS. These findings are preliminary, based on two small studies. PCOS is not associated with the most incessant forms of recurrent miscarriage. One small study found metformin may also decrease the incidence of gestational diabetes in PCOS women. The safety of Glucophage's use in pregnancy has not been established.
Metformin's effectiveness as a treatment for hirsutism have been mixed.

Metformin is chemically related to phenformin, which was withdrawn from the US market in 1976 because of a high association with lactic acidosis. With normal metformin dosing and normal renal function, development of lactic acidosis is very rare. It is prudent to verify a normal serum creatinine level before starting Metformin and to stop metformin treatment before conditions of relative renal compromise such as the administration of IV iodinated contrast agents and during fluid restriction. Cationic medications, such as cimetidine, compete with metformin for renal clearance thus increasing the risk of lactic acidosis.

Metformin's other contraindications are liver dysfunction, excessive alcohol intake, severe illness. The main side effects of metformin are GI: diarrhea, nausea. These effects can be mitigated by taking Glucophage with food and slowly building up to the target dosage of 1,500 to 2,000 mg total per day.
Metformin Summary:

<LI class=textnormal>PCOS is a syndrome, defined by unexplained hyperandrogenism and associated ovulatory dysfunction. Although not essential to its definition, PCOS will usually be accompanied by polycystic ovaries, and in about half the women, IR . <LI class=textnormal>IR is suggested clinically by central obesity and acanthosis nigricans. IR is a given with IGT or Type 2 Diabetes. Because of its high prevalence in PCOS, a strong case can be made for all women with PCOS to undergo an OGTT to detect IGT and Type 2 Diabetes. Unfortunately, proven practical means to screen for less advanced forms of IR are not established. Elevated fasting insulin levels and decreased fasting glucose insulin ratios (G/I < 4.5) are consistent with early IR, before beta cell exhaustion. With IGT or Type 2 Diabetes, the best intervention is weight loss and exercise. Metformin is generally the first choice among pharmacologic agents. <LI class=textnormal>For most women with PCOS trying to conceive, the first medication option to induce ovulation is still Clomid. However, metformin is arguably the first choice in women with IGT and certainly in women with type 2 diabetes. The combination of metformin and Clomid is effective. Weight loss and exercise promote ovulation. <LI class=textnormal>In women with PCOS not trying to conceive, menstrual irregularity is usually best treated with an estrogen-progestin contraceptive. In some women, it is possible that sustained metformin treatment may induce regular, ovulatory menstruation. <LI class=textnormal>In women with PCOS not trying to conceive, hirsutism treatment initially usually consists of an estrogen-progestin contraceptive, an anti-androgen such as spironolactone, and mechanical cosmetic treatment.
Metformin is a very safe medication when used properly and given to healthy women. It is contraindicated in women with renal compromise, liver disease, and at risk for lactic acidosis. GI side effects are initially very common, but usually are not

altabes · 05-30-2007, 03:28 PM

http://www.hormone.org/pdf/HF_Rosiglitazone.pdf

SarinaD · 06-04-2007, 11:12 PM

I want to thank you for posting this information. I don't post much, but I do lurk....

I had been on Avandia for almost 6 months and it essentially did nothing to help me. I gained 15 lbs while one it and was fed up with the edema. I had been to the doctor 3 times due to the edema it was causing.

About 3 weeks ago, I decided to go off of it and now I am even more glad that I did!