Efficacy and safety of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in hemodialysis patients with diabetic nephropathy: A randomized open-label prospective trial

Diabetes Res Clin Pract. 2016 Jun:116:244-52. doi: 10.1016/j.diabres.2016.04.034. Epub 2016 Apr 26.

Abstract

Aims: Saxagliptin is a dipeptidyl peptidase-4 inhibitor that was approved in Japan for the treatment of type 2 diabetes in 2013. We examined its efficacy and safety in Japanese hemodialysis patients with diabetic nephropathy.

Methods: In this prospective, open-label, parallel-group study, Japanese hemodialysis patients were randomized to receive either oral saxagliptin (2.5mg/day) or usual care (control group) for 24weeks. Before randomization, patients received fixed doses of conventional antidiabetic drugs (oral drugs and/or insulin) for 8weeks; these drugs were continued during the study. Endpoints included changes in glycated albumin (GA), hemoglobin A1c (HbA1c), postprandial plasma glucose (PPG), and adverse events.

Results: Both groups included 41 patients. Mean GA, HbA1c, and PPG decreased significantly in the saxagliptin group (-3.4%, -0.6% [-7mmol/mol], and -38.3mg/dL, respectively; all P<0.0001) but not in the control group (0%, -0.1% [-1mmol/mol], and -3.7mg/dL, respectively) (P<0.0001, P<0.001, and P<0.0001, respectively). In saxagliptin-treated patients, the reduction in GA was significantly greater when saxagliptin was administered as monotherapy than in combination therapy (-4.2% vs. -3.0%, P=0.012) despite similar baseline values (24.5% vs. 23.3%). Reductions in GA, HbA1c, and PPG were greater in patients whose baseline values exceeded the median (23.8% for GA, 6.6% for HbA1c, and 180mg/dL for PPG). There were no adverse events associated with saxagliptin.

Conclusions: Saxagliptin (2.5mg/day) was effective and well tolerated when used as monotherapy or combined with other antidiabetic drugs in Japanese hemodialysis patients with type 2 diabetes.

Clinical trial registration number: UMIN000018445.

Keywords: Glycated albumin; Hemodialysis; Saxagliptin; Type 2 diabetes.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / drug therapy*
  • Dipeptides / adverse effects
  • Dipeptides / therapeutic use*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / drug effects
  • Glycated Hemoglobin / metabolism
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Japan
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis*
  • Serum Albumin / drug effects
  • Serum Albumin / metabolism

Substances

  • Blood Glucose
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Hypoglycemic Agents
  • Serum Albumin
  • saxagliptin
  • Adamantane
  • Glycated Serum Albumin