Objective: Patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease have an increased risk of micro- and macrovascular disease, but limited options for antihyperglycemic therapy. We compared the efficacy and safety of sitagliptin with glipizide in patients with T2DM and moderate-to-severe chronic renal insufficiency and inadequate glycemic control.
Research design and methods: Patients (n = 426) were randomized 1:1 to sitagliptin (50 mg every day [q.d.] for moderate renal insufficiency and 25 mg q.d. for severe renal insufficiency) or glipizide (2.5 mg q.d., adjusted based on glycemic control to a 10-mg twice a day maximum dose). Randomization was stratified by: 1) renal status (moderate or severe renal insufficiency); 2) history of cardiovascular disease; and 3) history of heart failure.
Results: At week 54, treatment with sitagliptin was noninferior to treatment with glipizide in A1C change from baseline (-0.8 vs. -0.6%; between-group difference -0.11%; 95% CI -0.29 to 0.06) because the upper bound of the 95% CI was less than the prespecified noninferiority margin of 0.4%. There was a lower incidence of symptomatic hypoglycemia adverse events (AEs) with sitagliptin versus glipizide (6.2 and 17.0%, respectively; P = 0.001) and a decrease in body weight with sitagliptin (-0.6 kg) versus an increase (1.2 kg) with glipizide (difference, -1.8 kg; P < 0.001). The incidence of gastrointestinal AEs was low with both treatments.
Conclusions: In patients with T2DM and chronic renal insufficiency, sitagliptin and glipizide provided similar A1C-lowering efficacy. Sitagliptin was generally well-tolerated, with a lower risk of hypoglycemia and weight loss versus weight gain, relative to glipizide.