Metformin Prevents Type 2 Diabetes After Gestational Diabetes

Jenni Laidman

February 26, 2015

Both lifestyle intervention and use of the drug metformin reduced the risk for type 2 diabetes among women with a history of gestational diabetes mellitus (GDM) in a 10-year study.

But metformin failed to affect diabetes risk among those without a history of GDM, according to this new analysis of the Diabetes Prevention Program Outcomes Study (DPPOS), published online February 23 in the Journal of Clinical Endocrinology & Metabolism by Vanita R Aroda, MD, from MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

"This is probably the longest-term look at progression to [type 2] diabetes for women with a history of gestational diabetes," Dr Aroda told Medscape Medical News.

The results confirm that pregnancy operates like a "stress test for the body," signaling a high probability of progression to diabetes, she said. "It's important to assess whether a woman had gestational diabetes. People tend to forget about it after the baby is delivered, but long after the baby is delivered the risk is quite high, and this study shows one can do something about it."

Indeed, says coauthor William Herman, MD, MPH, from the University of Michigan, Ann Arbor, "This really emphasizes in my mind that metformin is a viable alternative to lifestyle intervention among women with a history of gestational diabetes."

Women With Gestational Diabetes at Higher Risk for Type 2 Diabetes

The women studied were part of the DPPOS, which is a long-term follow-up of the 3-year Diabetes Prevention Program (DPP), which randomized overweight or obese people at high risk for type 2 diabetes to intensive lifestyle change that included a goal of 7% weight loss and 150 minutes or more per week of moderate-intensity physical exercise; 850 mg of metformin twice daily; or placebo.

There were 3234 participants originally enrolled, with a mean body mass index (BMI) of 34 kg/m2. Of DPP participants, 68% were women and 45% were from ethnic minority groups.

The most recent results from the overall DPPOS/DPP study were reported at the American Diabetes Association meeting last year, showing that intensive lifestyle change or giving metformin can reduce or delay the development of type 2 diabetes for as long as 15 years, in some cases. These data also hinted at a stronger effect of both the lifestyle intervention and metformin compared with placebo in women with prior gestational diabetes.

This new analysis specifically examined 350 women with a history of GDM and 1416 women with previous live births but no gestational diabetes from DPPOS.

Women with a history of GDM assigned to the placebo group had a 48% higher risk of progressing to type 2 diabetes than women without a history of gestational diabetes.

Among those who had had gestational diabetes, both intensive lifestyle intervention and metformin reduced progression to diabetes compared with placebo — by 35% and 40% respectively.

However, among women with no prior GDM, metformin had no impact while intensive lifestyle intervention reduced progression to diabetes by 30%, although this latter finding differed by age.

Among the 325 women 25 to 44 years old without a history of GDM, neither intensive lifestyle intervention nor metformin reduced progression to diabetes.

But women 60 and older who'd not had gestational diabetes saw a 41% reduction in progression to diabetes with intensive lifestyle, although metformin did not have any effect.

The finding that metformin fails to halt diabetes progression in women without a history of gestational diabetes is unique, as the drug also effectively prevents progression to diabetes in young men.

"That was kind of surprise finding," Dr Aroda told Medscape Medical News. "We saw it in the 3-year follow-up and now it's confirmed."

Diabetes Risk Persists After GDM Even Years Down the Line

Although the greatest risk for type 2 diabetes was in the first 5 years after pregnancy, the chance of diabetes developing did not disappear after this period, said Dr Aroda.

"You see the risk sustained after 10 years. By entry into our study, these women were probably 12 years away from their pregnancy, but they are still at high risk," she explained.

In a number-needed-to-treat analysis, the study found seven women with GDM would need to receive metformin to prevent one case of type 2 diabetes within 10 years, and 11 women with GDM would need to participate in intensive lifestyle modification to prevent one case of diabetes in 10 years.

Among women who had given birth with impaired glucose tolerance but no gestational diabetes, 10 women would need to participate in intensive lifestyle modification to prevent one diabetes case.

The results of this longer-term study are consistent with the initial DPP results and confirm the importance of metformin, Dr Herman told Medscape Medical News.

"My clinical sense is a woman with a history of GDM has other things on her mind, like taking care of the infant, and a lifestyle intervention may not suit her lifestyle or her schedule," he observed. "So metformin is as effective as lifestyle: when her life becomes saner, she may be able to switch to the other."

This work was supported by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Dr Aroda has no relevant financial relationships. Disclosures for the coauthors are listed in the article. Dr Herman has no relevant financial relationships.

J Clin Endocrinol Metab. Published online February 23, 2015. Abstract

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