Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial

Ann Intern Med. 1999 Aug 3;131(3):182-8. doi: 10.7326/0003-4819-131-3-199908030-00004.


Background: Patients with type 2 diabetes are often obese and require large doses of insulin to achieve glycemic control. Weight gain often accompanies insulin therapy and results in increasing insulin requirements.

Objective: To evaluate the efficacy of metformin in combination with insulin in patients with type 2 diabetes poorly controlled with insulin therapy alone.

Design: Randomized, double-blind, placebo-controlled trial.

Setting: Outpatient diabetes clinic at a university medical center.

Patients: 43 patients with poorly controlled type 2 diabetes who were receiving insulin therapy.

Intervention: Patients were randomly assigned to receive placebo or metformin in combination with insulin for 24 weeks.

Results: Hemoglobin A1c levels decreased by 2.5 percentage points (95% CI, 1.8 to 3.1 percentage points) in the metformin group, a significantly greater change (P = 0.04) than the decrease of 1.6 percentage points in the placebo group. Average final hemoglobin A1c levels were 6.5% in the metformin group and 7.6% in the placebo group (difference, 11%). For patients who received placebo, the insulin dose increased 22.8 units (CI, 11 to 44 units) or 29% more than did the dose for patients who received metformin (P = 0.002); for these patients, the insulin dose decreased slightly. Patients in the placebo group gained an average of 3.2 kg of body weight (CI, 1.2 to 5.1 kg); patients in the metformin group gained an average of 0.5 kg of body weight (P = 0.07). Total cholesterol and low-density lipoprotein cholesterol levels decreased in both groups. High-density lipoprotein cholesterol and triglyceride levels did not change.

Conclusions: The addition of metformin to insulin therapy resulted in hemoglobin A1c concentrations that were 10% lower than those achieved by insulin therapy alone. This improvement in glycemic control occurred with the use of 29% less insulin and without significant weight gain. Metformin is an effective adjunct to insulin therapy in patients with type 2 diabetes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose / metabolism
  • Body Weight
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diet therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Energy Intake
  • Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / therapeutic use*
  • Lipids / blood
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Obesity / complications
  • Statistics, Nonparametric


  • Blood Glucose
  • C-Peptide
  • Hypoglycemic Agents
  • Insulin
  • Lipids
  • Hemoglobin A
  • Metformin