The Effects of Novel Antidiabetic Drugs on Albuminuria in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Clin Drug Investig. 2018 Dec;38(12):1089-1108. doi: 10.1007/s40261-018-0707-4.

Abstract

Background and objective: The effects of novel antidiabetic drugs, including sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors, on albuminuria in patients with type 2 diabetes mellitus (T2DM) are still controversial. Therefore, we performed a meta-analysis to evaluate the effects of novel antidiabetic drugs on albuminuria in patients with T2DM.

Methods: We conducted a random-effects meta-analysis of randomized controlled trials (RCTs) by searching the MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases up to 16 August 2018. The effects of novel antidiabetic drugs on albuminuria were evaluated as percent changes from baseline to follow-up urinary albumin excretion/urinary albumin to creatinine ratio (UAE/UACR) levels in both the intervention and control groups. Data regarding percent changes were used to generate weighted mean differences (WMDs) and 95% confidence intervals (CIs).

Results: In this meta-analysis, 26 RCTs involving 14,929 patients were included. Pooled analysis suggested that SGLT-2 inhibitors (WMD - 26.23%, 95% CI - 35.90 to - 16.56; p < 0.00001) and GLP-1 receptor agonists (WMD - 13.85%, 95% CI - 15.96 to - 11.74; p < 0.00001) were associated with a significant reduction in albuminuria compared with other conventional therapies or placebo. DPP-4 inhibitors (WMD - 6.19%, 95% CI - 14.03 to 1.66; p = 0.12) were not significantly associated with lower albuminuria than other conventional therapies or placebo.

Conclusion: This meta-analysis indicates that SGLT-2 inhibitors and GLP-1 receptor agonists were associated with a reduction in albuminuria compared with other conventional therapies or placebo, while DPP-4 inhibitors were not associated with albuminuria-reducing effects compared with other conventional therapies or placebo.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Albuminuria / drug therapy*
  • Albuminuria / epidemiology
  • Albuminuria / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Hypoglycemic Agents / metabolism
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Randomized Controlled Trials as Topic / methods*
  • Sodium-Glucose Transporter 2 / metabolism
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2