Insulin Monotherapy vs. Combination Therapy

Clinical Question

Are combinations of insulin and oral agents more effective than insulin monotherapy in patients with type 2 diabetes mellitus?

Evidence-Based Answer

NPH insulin and metformin taken at bedtime appears to be the most favorable combination studied, but this conclusion is based on poor-quality, inconsistent studies that measure disease-oriented outcomes. There are no data on the effect of these drug combinations on patient-oriented outcomes.

Practice Pointers

Goudswaard and colleagues identified 20 randomized controlled trials (RCTs) with a total of 1,811 patients. The RCTs included 28 comparisons of insulin monotherapy with a combination of insulin and a sulfonylurea, metformin, or both. About one half of the patients were women. The mean age was 60 years, and patients had type 2 diabetes for a mean of 10 years. None of the studies assessed diabetic complications, diabetes-related mortality, or total mortality. In the United Kingdom Prospective Diabetes Study, treatment of overweight patients with insulin or sulfonylureas had no effect on individual or aggregate microvascular or macrovascular outcomes (36.8 versus 38.9 events per 1,000 patient years).^1,2

The identified RCTs were fair quality, with a mean score of 2.8 on a seven-point quality scale. Most did not clearly describe how patients were allocated to treatment groups, and 11 RCTs did not blind patients, physicians, or persons evaluating outcomes. A variety of regimens were compared, and results were combined where appropriate. Differences between insulin monotherapy and combination approaches generally were small and inconsistent. The combination of an oral agent and insulin typically resulted in a slightly lower hemoglobin A1C level (0.1 to 0.4 percent), a difference that is unlikely to be clinically important. Patients taking the combination of insulin and metformin were less likely to gain weight than those taking insulin alone, but this combination was examined only in a single, relatively small RCT. There was no difference between groups in the likelihood of symptomatic hypoglycemia.