For patients with type 2 diabetes, treatment with metformin and insulin has no significant effect on all-cause or cardiovascular mortality, compared with insulin alone, although data are limited and suffer from bias, according to a meta-analysis published online the British Medical Journal.
Bianca Hemmingsen, from the Copenhagen University Hospital in Denmark, and colleagues reviewed the literature to compare the benefits and harms of metformin and insulin versus insulin alone for type 2 diabetes. A total of 23 randomized clinical trials were eligible, involving 2,117 patients with diabetes; all of the trials had a high risk of bias.
The researchers found that, compared with insulin alone, metformin and insulin had no significant effect on all-cause mortality or cardiovascular mortality. Before reliable conclusions could be drawn regarding these outcomes, trial sequential analyses showed that more trials were needed. Severe hypoglycemia was significantly more frequent with metformin and insulin versus insulin alone in the fixed, but not random, effect model. Compared with insulin alone, metformin and insulin lead to a reduction in glycated hemoglobin, weight gain, and insulin dose in a random effects model. Based on trial sequential analyses, the evidence was sufficient for a 0.5 percent reduction in glycated hemoglobin, 1 kg lower weight, and insulin dose reduction of 5 U/day with metformin and insulin.
“There was no evidence or even a trend towards improved all-cause mortality or cardiovascular mortality with metformin and insulin, compared with insulin alone in type 2 diabetes,” the authors wrote.