Metformin Particularly Effective in Those With History of GDM

Norra MacReady

June 29, 2017

SAN DIEGO — Long-term use of metformin shows a particularly strong effect in preventing the development of type 2 diabetes among women who've had gestational diabetes, according to data presented at the American Diabetes Association (ADA) 2017 Scientific Sessions.

These latest findings come from the Diabetes Prevention Program (DPP) and its extension phase.

After 15 years from the start of DPP, women with a history of gestational diabetes taking metformin still had a 41% reduced risk of type 2 diabetes, compared with an 11% reduction in parous women with no history of gestational diabetes.

This contrasts with an overall effect of metformin in reducing the risk of type 2 diabetes by 18% in the study cohort as a whole.

"The overall results reinforce the long-lasting efficacy of metformin in reducing the development of diabetes and support its more widespread use as a prevention measure in those at high risk," said David M Nathan, MD, director of the Diabetes Center at Massachusetts General Hospital, Boston, the study chair of DPP, who presented these latest results at the conference.

Asked for comment, Shubhada Jagasia, MD, professor of medicine and vice chair of clinical affairs in the department of medicine, Vanderbilt University Medical Center, Nashville, Tennessee, told Medscape Medical News that these new data should help doctors to target metformin treatment to those who will benefit most.

DPP: An Ongoing Investigation

DPP started in 1996 and followed individuals who were at high risk of diabetes on the basis of body mass index (BMI) and impaired glucose tolerance. They were randomized to one of three groups: intensive lifestyle interventions with diet and exercise, 850-mg metformin twice a day, or placebo. DPP ran through 2002 and compared the incidence of diabetes — defined as a fasting plasma glucose of 126 mg/dL or greater, or a 2-hour oral glucose tolerance test of 200 mg/dL or more — in each of the groups.

As has already been reported, those in the placebo group developed diabetes at a rate of 11% per year, while the lifestyle intervention was associated with a 58% decrease in the risk of diabetes and metformin was linked to a 31% reduction in risk.

In that original analysis, metformin reduced the risk of future diabetes by 51% in women with a history of gestational diabetes. Two other subgroups of patients also seemed to gain greater benefit from metformin — those younger than 60 years of age and those with a BMI >35 kgm2.

At the conclusion of the DPP, the placebo was stopped, and all patients were offered a slightly different lifestyle intervention. In addition, metformin continued to be provided to the people in the original metformin group. This extension phase — known as the Diabetes Prevention Program Outcomes Study (DPPOS) — was started in 2003 and is still ongoing, with 88% of the original volunteers still participating.

Over time, the 31% reduction in diabetes risk initially seen with metformin waned to 18% by 10 years and has remained stable, so "an 18% reduction is the overall result, compared with people in the original placebo group," Dr Nathan pointed out.

At 15 years, the differences between the subgroups in the benefits of metformin also waned, so that the effects of metformin were for the most part no longer significantly different in these subgroups, with the exception of the women with a history of gestational diabetes.

Clinical Implications

When considering which of their patients should receive metformin, clinicians should now "be more likely to prescribe it" to women with a history of gestational diabetes, "who were shown in this study to have the biggest impact in terms of diabetes reduction," said Dr Jagasia.

"These are the patients in whom we would be more likely to go the metformin route if for any reason intensive lifestyle modification or a 5% to 10% reduction in body weight is not possible," she added.

However, lifestyle modification should always be tried first, she stressed to Medscape Medical News. "Whenever clinicians prescribe medication for diabetes, it is always in addition to lifestyle changes."

Dr Nathan reports no relevant financial relationships. Disclosures for the coauthors are listed in the abstract. Dr Jagasia disclosed no relevant financial relationships.

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American Diabetes Association 2017 Scientific Sessions. June 11, 2017; San Diego, California. Abstract 169-OR


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