title: Efficacy and safety of sitagliptin versus glipizide in patients with type 2 diabetes and moderate-to-severe chronic renal insufficiency.
abstract: 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.
  
  
  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.
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA. juan_arjona@merck.com
authors.forename: Juan Camilo
authors.initials: JC
authors.lastname: Arjona Ferreira
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golm
authors.forename: Christine McCrary
authors.initials: CM
authors.lastname: Sisk
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005913:Glipizide / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D011719:Pyrazines / Q000009:adverse effects* / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000097:blood*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate; D005913:Glipizide