Glyburide Versus Metformin and Their Combination for the Treatment of Gestational Diabetes Mellitus: A Randomized Controlled Study

Diabetes Care. 2017 Mar;40(3):332-337. doi: 10.2337/dc16-2307. Epub 2017 Jan 11.


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.

Trial registration: NCT01563120.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Blood Glucose / metabolism
  • Diabetes, Gestational / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Glyburide / administration & dosage*
  • Glyburide / adverse effects
  • Humans
  • Hypoglycemia / etiology
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Israel
  • Metformin / administration & dosage*
  • Metformin / adverse effects
  • Middle Aged
  • Pregnancy
  • Prospective Studies
  • Sample Size
  • Treatment Failure
  • Treatment Outcome
  • Young Adult


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Metformin
  • Glyburide

Associated data