Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Endocrinol Metab (Seoul). 2019 Mar;34(1):80-92. doi: 10.3803/EnM.2019.34.1.80.

Abstract

Background: To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.

Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome.

Results: We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (P=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; P=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; P=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; P<0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, -1.11 mL/min/1.73 m²; 95% CI, -1.78 to -0.44; P=0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; P=0.475).

Conclusion: DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.

Keywords: Albuminuria; Diabetes complications; Diabetes mellitus, type 2; Diabetic nephropathies; Dipeptidyl-peptidase IV inhibitors; Glomerular filtration rate; Kidney failure, chronic; Meta-analysis; Systematic review.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Albumins / drug effects*
  • Albuminuria / prevention & control*
  • Diabetes Complications / epidemiology
  • Diabetes Complications / prevention & control
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / prevention & control
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Failure, Chronic / etiology
  • Middle Aged
  • Placebos / administration & dosage
  • Randomized Controlled Trials as Topic

Substances

  • Albumins
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Placebos