Glyburide vs. Metformin during pregnancy

This randomized controlled study shows that glyburide and metformin are comparable in management of gestational diabetes. There is tendency for metformin to be somewhat superior however, given less insulin use as second line therapy.


Diabetes Care

Randomized Trial

April 2017

Objective: To compare the efficacy and safety of glyburide versus metformin and their combination for the treatment of gestational diabetes mellitus (GDM).

Research design and methods: In this prospective randomized controlled study, we randomly assigned patients with GDM at 13–33 weeks gestation and whose blood glucose was poorly controlled by diet to receive either glyburide or metformin. If optimal glycemic control was not achieved, the other drug was added. If adverse effects occurred, the drug was replaced. If both failed, insulin was given. The primary outcomes were the rate of treatment failure and glycemic control after the first-line medication according to mean daily glucose charts.

Results: Glyburide was started in 53 patients and metformin in 51. In the glyburide group, the drug failed in 18 (34%) patients due to adverse effects (hypoglycemia) in 6 (11%) and lack of glycemic control in 12 (23%). In the metformin group, the drug failed in 15 (29%) patients, due to adverse effects (gastrointestinal) in 1 (2%) and lack of glycemic control in 14 (28%). Treatment success after second-line therapy was higher in the metformin group than in the glyburide group (13 of 15 [87%] vs. 9 of 18 [50%], respectively; P = 0.03). In the glyburide group, nine (17%) patients were eventually treated with insulin compared with two (4%) in the metformin group (P = 0.03). The combination of the drugs reduced the need for insulin from 33 (32%) to 11 (11%) patients (P = 0.0002). Mean daily blood glucose and other obstetrical and neonatal outcomes were comparable between groups, including macrosomia, neonatal hypoglycemia, and electrolyte imbalance.

Conclusions: Glyburide and metformin are comparable oral treatments for GDM regarding glucose control and adverse effects. Their combination demonstrates a high efficacy rate with a significantly reduced need for insulin, with a possible advantage for metformin over glyburide as first-line therapy.

More from the article:

Oral hypoglycemic agents for treating gestational diabetes mellitus (GDM) have gained popularity since the studies of Langer et al. and Rowan et al., which demonstrated glyburide (glibenclamide) and metformin to be good alternatives for insulin. Oral hypoglycemic agents are an attractive option to insulin because of their lower cost and ease of administration, which increase patient compliance. On the basis of a meta-analysis comparing glyburide and metformin with insulin that found similar efficacy and safety for both mothers and neonates, oral hypoglycemic agents are now acceptable medications to treat GDM in official guidelines; glyburide became the most common first-line medication for GDM in the U.S.

To our knowledge, use of additional oral medication in the case of poor glycemic control with a single agent or switching to another oral medication in case of adverse effects with the first-line medication has not been explored. Therefore, the current study aimed to compare the efficacy and safety of glyburide versus metformin in the treatment of GDM and to evaluate the improvement in glycemic control after their replacement as a result of adverse effects or after the addition of the second drug because of failure of the first.

This study compared the efficacy and safety of glyburide and metformin for the treatment of GDM. In this randomized controlled trial, both treatments were similar in their efficacy and safety. The current study is original in two respects. First, it was designed to answer two primary outcomes: glycemic control and treatment failure as a result of either poor glycemic control or adverse effects. We chose to add treatment failure as a primary outcome, as opposed to previous studies, because we believed that this outcome better answers which drug is superior, which particularly holds true in the case of glycemic control eventually being achieved in both groups with insulin (with which treatment failure is rare). Second, this study examined the usefulness of the second oral hypoglycemic agent as second-line therapy and insulin only as a third-line therapy. To our knowledge, this study is the first to examine this objective. We hypothesized that because the two medications act with different mechanisms, one would succeed where the other failed to achieve glycemic control and particularly if the medication was discontinued because of adverse effects. This strategy raised treatment success from 69% to 89%, leading to only 11% of the patients needing insulin. These results support the benefit of using an additional oral hypoglycemic agent in the case of a treatment failure before switching to insulin.

The patients who started with metformin had a lower probability of requiring insulin. We speculate that this finding is a result of the rate of treatment failure due to adverse effects (although it did not reach statistical significance) being lower in the metformin group than in the glyburide group; therefore, more patients used both medications simultaneously for poor glycemic control. In addition, because metformin increases insulin sensitivity, it might have potentiated the effect of glyburide when the later was added.

In conclusion, glyburide and metformin are comparable oral treatments for GDM regarding glucose control and treatment failure. Their combination allows a higher efficacy rate with a significant reduced need for insulin that should be reserved for patients who failed to respond to both oral treatments or who experienced adverse effects as a result of both.