The addition of off-label metformin to insulin therapy to improve insulin sensitivity, promote weight control, and reduce insulin dose requirements in patients with type 1 diabetes, has been assessed in systematic reviews.…
At what point, if any, should one consider the addition of metformin to the regimen of an adherent patient with type 1 diabetes who is not well controlled on insulin?
One review sought to assess the effects of metformin when added to insulin therapy for type 1 diabetes in adolescents. The Cochrane Library, MEDLINE, and EMBASE were searched, along with databases of ongoing clinical trials, for randomized controlled trials of at least 3 months’ duration. Trials that were included compared metformin added to insulin vs. insulin therapy alone. Two trials met inclusion criteria, representing 60 patients in total.
Although a lack of heterogeneity made meta-analysis impossible, the authors did note that both studies found a reduction in glycosylated hemoglobin A1c values when metformin was added to insulin. One of the studies also showed a 10% decrease in insulin dosage among those taking metformin. Hypoglycemia and gastrointestinal disturbances were among the most commonly occurring adverse effects of combination therapy.
Another systematic review evaluated the addition of metformin to insulin in type 1 diabetes. This review identified 9 studies, including both adolescents and adults, that involved randomization with informed consent. The studies compared metformin vs. placebo or another comparator in parallel or crossover design for at least 1 week.
Metformin use was associated with reduced insulin-dose requirement (reductions in total daily insulin of 5.7-10.1 units/day), A1c (reductions of 0.6%-0.9%), weight (range of weight loss, 1.7-6.0 kg), and total cholesterol (reduction of 11.6-15.8 mg/dL). Formal estimates of combined effects were possible from 5 studies which found a significant reduction in insulin dose of 6.6 units/day (P < .001) but a nonsignificant 0.11% reduction in A1c (P = .42). A trend existed towards an increase in hypoglycemia, reaching statistical significance in 2 of the studies evaluated.
Although clinical trial data are lacking to support or refute the use of off-label metformin in addition to insulin for type 1 diabetes, some patients with type 1 diabetes may benefit from the addition of metformin to their ongoing insulin regimen. The patients in whom it would make the most clinical sense to consider this are those who are overweight, require large doses of insulin, and/or continue to have uncontrolled A1c values despite adherence to insulin. Patients should be made aware that hypoglycemia may become more likely once metformin is added to their insulin regimen.
Abdelghaffar S, Attia AM. Metformin added to insulin therapy for type 1 diabetes mellitus in adolescents. Cochrane Database Syst Rev. 2009;(1):CD006691.
Vella S, Buetow L, Royle P, Livingstone S, Colhoun HM, Petrie JR. The use of metformin in type 1 diabetes: a systematic review of efficacy. Diabetologia. 2010;53:809-820.