Meglitinides increase the risk of hypoglycemia in diabetic patients with advanced chronic kidney disease: a nationwide, population-based study

The safety of short-acting meglitinides in diabetic patients with advanced chronic kidney disease (CKD) has not been widely reported. Diabetic patients with advanced CKD who had a serum creatinine level of > 6 mg/dL a hematocrit level of <= 28% and received erythropoiesis-stimulating agent treatment between 2000 and 2010, were included in this nationwide study in Taiwan. The outcomes of interest were defined as hypoglycemia and long-term mortality. The risks of hypoglycemia and death were analyzed using Cox proportional hazards models, with end-stage renal disease and anti-diabetic drugs as time-dependent variables. Fresh users and matched non-users of meglitinides (both n = 2,793) were analyzed. The use of meglitinides increased the risk of hypoglycemia (HR, 1.94, p<0.001), as did other anti-diabetic agents. Concomitant use of meglitinide and insuilin will incresase the hypoglycemic risk. (HR, 1.69, p=0.018) Moreover, it was not the use of meglitinides, but the presence of hypoglycemia that predicted mortality. The function curve showed an insignificant trend towards increased hypoglycemic risk in patients aged > 62 and = 33 years from the generalized additive model. This study suggests that the use of short-acting meglitinides could be associated with increased risk of hypoglycemia in diabetic patients with advanced CKD, especially in patients aged > 62 and = 33 years. Meglitinide combined with insulin will increase hypoglycemia in patients with advanced CKD.