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ARTICLE

Effects of Metformin in Patients with Poorly Controlled, Insulin-Treated Type 2 Diabetes Mellitus

A Randomized, Double-Blind, Placebo-Controlled Trial

Larissa Avilés-Santa, MD; Joyce Sinding, MSN, RN; and Philip Raskin, MD

3 August 1999 | Volume 131 Issue 3 | Pages 182-188

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 medicalcenter.

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 A_1c 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 A_1c 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 A_1c 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 isan effective adjunct to insulin therapy in patients with type 2 diabetes.

Author and Article Information

From University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.

Acknowledgments: The authors are indebted to Susan Cercone, RD, MSD, CDE, for her assistance in obtaining and evaluating diet histories and Dr. William Frawley, biostatistician at the University of Texas Southwestern Medical Center, whose comments were invaluable in the preparation of the manuscript.

Grant Support: In part by a grant from Bristol-Myers Squibb (Protocol 7034-BS).

Requests for Reprints: Philip Raskin, MD, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard G5.238, Dallas, TX 75235-8858.

Current Author Addresses: Drs.Avilés-Santa and Ms. Sinding: University of Texas SouthwesternMedical Center, 5323 Harry Hines Boulevard G4.100, Dallas, TX 75235-8858.

Dr. Raskin: University of Texas SouthwesternM edical Center, 5323 Harry Hines Boulevard G5.238, Dallas, TX 75235-8858.

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