Glyburide and metformin, separately or together, treat gestational diabetes

By Marilynn Larkin

NEW YORK (Reuters Health) - Glyburide and metformin have comparable efficacy in controlling glucose in gestational diabetes, and their combination significantly reduces the need for insulin, researchers in Israel report.

Although oral hypoglycemic agents "seem promising," study results have been conflicting, Drs. Zohar Nachum and Enav Yefet of Emek Medical Center Afula and colleagues write in Diabetes Care, online January 11.

To investigate, the team randomly assigned women with gestational diabetes at 13 to 33 weeks gestation whose blood glucose was poorly controlled by diet to receive glyburide or metformin. If either drug alone did not achieve glycemic control, the other was added. If adverse events occurred, the drug was replaced. If both drugs failed, insulin was given.

Fifty-three women initially received glyburide and 51 were given metformin. Glyburide failed in 18 (34%) patients - six (11%) due to hypoglycemia and 12 (23%) due to lack of glycemic control. Metformin failed in 15 (29%) patients - one (2%) due to adverse gastrointestinal effects and 14 (28%) due to lack of glycemic control.

Treatment success after second-line therapy was higher in the metformin than in the glyburide group (87% versus 50%, respectively; P=0.03). Nine (17%) patients in the glyburide group eventually were treated with insulin compared with two (4%) in the metformin group (P=0.03).

Overall, combining the two drugs reduced the need for insulin from 33 (32%) to 11 (11%) women (P=0.0002).

Mean daily blood glucose and other outcomes were comparable between groups, including macrosomia, neonatal hypoglycemia and electrolyte imbalance.

Drs. Nachum and Yefet told Reuters Health, "The key message of this study is that glyburide and metformin are comparable oral treatments for gestational diabetes mellitus regarding glucose control and treatment failure. Their combination allows a higher efficacy rate with significant reduced need for insulin, probably due to their different mechanisms of action and adverse effect profiles."

"In addition, although not studied directly, the need for insulin was lower if metformin was used as the first-line therapy," they said by email. "This observation was also shown in some . . . studies that have been published recently."

"We speculate that this result might be because the rate of treatment failure due to adverse effects (although it did not reach statistical significance) was lower in the metformin group compared to glyburide group and therefore, more women used both medications simultaneously for poor glycemic control," they add. "Since metformin increases insulin sensitivity, it might potentiate the effect of glyburide when the latter was added."

Dr. Shubhada Jagasia of Vanderbilt University Medical Center in Nashville, Tennessee, told Reuters Health by email, "This is an interesting study, which has further bolstered confidence in the use of metformin as a treatment option for gestational diabetes mellitus."

"These results, if reproduced in additional studies, will certainly provide greater oral medication options for management of gestational diabetes, especially since many pregnant patients do not have access to maternal fetal medicine specialists and endocrinologists who may be needed to manage complicated insulin treatment regimens," she observed.

"Oral treatments will also reduce costs of therapy," Dr. Jagasia continued. "Monotherapy with either glyburide or metformin, in previous studies, has been associated with a high failure rate of approximately 30%. Combination oral therapy with glyburide and metformin seems to be associated with a much lower failure rate of approximately 10%."

"I personally use only insulin and glyburide as my therapeutic options in the treatment of gestational diabetes," she added. "Although the immediate efficacy of metformin has been shown in recent studies, the long-term impact of in utero exposure to metformin is essentially unknown."

SOURCE: https://bit.ly/2kuamYp

Diabetes Care 2017.

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