Effect of new anti-diabetic medications in combination with metformin compared to sulfonylurea in combination with metformin in patients with type 2 diabetes

Type 2 diabetes is a serious, chronic disease that can increase the risk of death, heart attack, stroke and kidney disease. This overview of reviews updates evidence comparing the effects of the currently recommended treatment (sulfonylurea + metformin) to treatment with newer anti-diabetic mediations (DPP-4 inhibitors or GLP-1 analogs) added to metformin when neither life-style changes nor metformin alone are effective in reducing blood sugar levels. No conclusions can be drawn about the effect on mortality of adding DPP-4 inhibitor versus sulfonylurea to metformin because of few events and low quality evidence. There was no documentation for the effect on mortality of adding GLP-1 analogs versus sulfonylurea to metformin. We found no evidence on the effects on micro and macrovascular complications for either comparison. Results for intermediate outcomes (HbA1c change, weight, hypoglycemic incidents) are mixed. Reduction in HbA1c is larger with sulfonylurea, but DPP-4 inhibitors and GLP-1 analogs result in more weight loss and a lower risk of a hypoglycemic episode. All differences are small in magnitude and may be clinically unimportant. Sulfonylurea + metformin is substantially less costly than either DPP-4 inhibitors or GLP-1 analogs + metformin.