Combination therapy with insulin and metformin

To review the clinical usefulness of combination therapy with insulin and metformin.

Basic considerations about the use of insulin in non-insulin-dependent diabetes mellitus (NIDDM) and the interaction of metformin with insulin are outlined. The clinical documentation of this therapeutic strategy is reviewed, with emphasis on controlled studies. In addition, the use of this drug combination in insulin-dependent diabetes mellitus (IDDM) is briefly addressed.

Insulin is used in patients with NIDDM when adequate plasma glucose control can no longer be maintained by orally administered agents. Metformin ameliorates insulin resistance, reduces hyperinsulinemia, and counteracts weight gain. It exerts an insulin-sparing and antihyperglycemic effect and may improve cardiovascular risk factors. Although these effects have been demonstrated consistently in several controlled studies, relatively few patients have been treated with insulin + metformin (with or without sulfonylurea). The combination is well tolerated, commonly used, and approved in several countries. No specific guidelines have been established for selection of patients, but obese patients with NIDDM who are receiving high doses of insulin are likely to benefit. Patients whose diabetes is poorly controlled by sulfonylurea or by combination oral therapy, not previously treated with insulin, may also be suitable candidates. Insulin administered at bedtime is a feasible approach, and a daily dose of 1.5 to 2.5 g of metformin seems adequate. Although the application may be questionable, metformin can also be added to insulin in the treatment of selected patients with IDDM.

Metformin is effective in conjunction with insulin in NIDDM. Because of its action on insulin resistance, it might be a more suitable adjunct to insulin than sulfonylurea in obese patients with NIDDM who are receiving high insulin doses, but it has been less well studied.