Effects of once-weekly dulaglutide on kidney function in patients with type 2 diabetes in phase II and III clinical trials

Diabetes Obes Metab. 2017 Mar;19(3):436-441. doi: 10.1111/dom.12816. Epub 2016 Nov 24.

Abstract

Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes (T2D). Integrated data from 9 phase II and III trials in people with T2D (N = 6005) were used to evaluate the effects of dulaglutide on estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration]), urine albumin-to-creatinine ratio (UACR) and kidney adverse events (AEs). No significant differences in eGFR were observed during treatment for dulaglutide vs placebo, active comparators or insulin glargine (mean ± standard deviation values: dulaglutide vs placebo: 87.8 ± 17.7 vs 88.2 ± 17.9 mL/min/1.73 m2 , P = .075; dulaglutide vs active comparators: 89.9 ± 16.7 vs 88.8 ± 16.3 mL/min/1.73 m2 , P = .223; and dulaglutide vs insulin glargine: 85.9 ± 18.2 vs 83.9 ± 18.6 mL/min/1.73 m2 , P = .423). Lower UACR values were observed for dulaglutide vs placebo, active comparators and insulin glargine (at 26 weeks, median [Q1-Q3] values were: dulaglutide vs placebo: 8.0 [4.4-20.4] vs 8.0 [4.4-23.9] mg/g, P = .023; dulaglutide vs active comparators: 8.0 [4.4-21.2] vs 8.9 [4.4-27.4] mg/g, P = .013; and dulaglutide vs insulin glargine: 8.9 [4.4-29.2] vs 12.4 [5.3-50.5] mg/g, P = .029). AEs reflecting potential acute renal failure were 3.4, 1.7 and 7.0 events/1000 patient-years for dulaglutide, active comparators and placebo, respectively. In conclusion, dulaglutide treatment of clinical trial participants with T2D did not affect eGFR and slightly decreased albuminuria.

Keywords: GLP-1; clinical trial; diabetes complications; diabetic nephropathy; dulaglutide; type 2 diabetes.

Publication types

  • Comparative Study

MeSH terms

  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / metabolism
  • Aged
  • Albuminuria
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glomerular Filtration Rate
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Insulin Glargine / therapeutic use
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / therapeutic use*
  • Treatment Outcome

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Insulin Glargine
  • Glucagon-Like Peptides
  • Creatinine
  • dulaglutide