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


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Outpatient diabetes clinic at a university medical center.


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


METHODS
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.
Avilés-Santa
L
L
University of Texas Southwestern Medical Center at Dallas, 75235-8858, USA.
Sinding
J
J
Raskin
P
P
D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000178:diet therapy / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D002149:Energy Intake; D006441:Hemoglobin A / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications; D018709:Statistics, Nonparametric
D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D006441:Hemoglobin A; D008687:Metformin