Sitagliptin and glipizide monotherapy is safe and effective in patients with type 2 diabetes and end-stage renal disease (ESRD) requiring dialysis, researchers reported online ahead of print in the American Journal of Kidney Diseases.

Patients with type 2 diabetes mellitus and ESRD on dialysis therapy have limited therapeutic options to manage hyperglycemia, the researchers noted. Furthermore, few randomized controlled studies have evaluated or compared antihyperglycemic agents in this patient population.

These are the findings of a 54-week, randomized, double-blind study conducted by Juan C. Arjona Ferreira, MD, of Merck Sharp & Dohme Corp., in Whitehouse Station, N.J., and colleagues. The trial included 129 patients with type 2 diabetes and ESRD requiring dialysis. At baseline, patients had a hemoglobin A1c (HbA1c) level of 7%-9%. Of the 129 patients, 64 were assigned to treatment with sitagliptin and 65 were assigned to treatment with glipizide.

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For the study, patients received sitagliptin 25 mg daily or glipizide initiated with 2.5 mg daily and titrated up to a potential maximum dose of 10 mg twice daily or down to avoid hypoglycemia.

After 54 weeks, mean HbA1c levels declined significantly from baseline by 0.72% and 0.87% with sitagliptin and glipizide, respectively. Fasting plasma glucose levels declined significantly by 26.6 mg/dL and 31.2 mg/dL, respectively.

The incidences of symptomatic hypoglycemia were 6.3% in the sitagliptin group compared with 10.8% in the glipizide group, but the between-group difference was not significant. Severe hypoglycemia occurred in 7.7% of the glipizide-treated patients but not in any of the sitagliptin recipients, according to the investigators. The sitagliptin group had higher incidences of cellulitis and headache compared with the glipizide group.

Glipizide is one of two sulfonylureas recommended for use in patients with ESRD, but they are associated with an increased risk of hypoglycemia. Sitagliptin is a dipeptidyl peptidase 4 inhibitor that improves glycemic control and is associated with an incidence of hypoglycemia similar to that of placebo when used alone or with antihyperglycemic agents not associated with hypoglycemia, according to investigators. Sitagliptin is eliminated mostly through the kidneys, with approximately 80% of the oral dose excreted unchanged in urine.

“Based on the pharmacokinetics of sitagliptin, to achieve a plasma concentration of sitagliptin similar to that achieved with a once-daily 100-mg dose in patients with normal to mildly decreased kidney function, individuals with ESRD should receive one quarter of the usual clinical dose, or 25 mg daily,” the investigators noted.

The authors concluded that treatment with dose-adjusted sitagliptin provided clinically meaningful reductions from baseline in HbA1c and FPG levels similar to those observed with glipizide over 54 weeks in patients with type 2 diabetes and ESRD on dialysis therapy.