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Dipeptidyl peptidase-4 inhibitors (“gliptins”) are oral drugs used to treat patients with type 2 diabetes who don't respond to, or are intolerant of, metformin and those who don't achieve adequate glycemic control with other drugs, such as sulfonylureas. In this meta-analysis, researchers determined whether adding a gliptin to a sulfonylurea (usually glyburide or glimepiride) raises risk for hypoglycemia in people with type 2 diabetes.
Researchers analyzed data from 10 randomized, controlled trials (≈6500 participants; mean ages, 55–75; mean glycosylated hemoglobin levels, 7.7%–8.6%). Relative risk for hypoglycemia was 52% higher in participants who received gliptins and sulfonylureas than in those who received placebo and sulfonylureas. The number of patients who had to be treated with a gliptin to cause 1 episode of hypoglycemia (i.e., number needed to harm) decreased from 17 (for patients treated for ≤6 months) to 8 (for patients treated for >12 months). Results were similar when the researchers excluded trials in which insulin use was allowed and those that lacked clear definitions of hypoglycemia. Risk for hypoglycemia was similar for low- and high-dose gliptins.
Salvo F et al. Addition of dipeptidyl peptidase-4 inhibitors to sulphonylureas and risk of hypoglycaemia: Systematic review and meta-analysis. BMJ 2016 May 3; 353:i2231. (http://dx.doi.org/10.1136/bmj.i2231)
Comment
In this analysis, adding a gliptin to a sulfonylurea led to excess risk for hypoglycemia of more than 50%. These findings are not surprising: Sulfonylureas raise insulin levels directly and are a well-known cause of hypoglycemia, whereas gliptins raise incretin levels, which inhibit glucagon release and raise insulin levels indirectly. The authors recommend decreasing sulfonylurea doses when initiating gliptins.