Exenatide and renal outcomes in patients with type 2 diabetes and diabetic kidney disease: a multi-center, randomized, parallel study

Abstract Background: This trial aimed to assess the effects of exenatide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), on renal outcomes in patients with type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD).Methods: We performed a randomized, parallel study conducted in 4 general hospitals. T2DM patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73m2 and macroalbuminuria, defined as 24-hour urinary albumin excretion rate (UAER) >0.3 g/24-h, were randomized 1:1 to receive exenatide twice daily plus insulin glargine or insulin lispro plus glargine for 24 weeks. The primary outcome was percentage change in UAER after 24 weeks of intervention comparing to baseline measurement. Rates of hypoglycemia, adverse events and change in eGFR during the follow up were set as safety outcomes.Results: Between March 2016 and April 2019, 92 patients were randomized and took at least one dose of study drug. The mean age of the participants was 56 years. At baseline, the median UAER was 1512.0 mg/24-h, and mean eGFR was 70.4 mL/min/1.73 m2. After 24 weeks, exenatide reduced 29.7% of the UAER (p = 0.0255). Meanwhile, the body weight declined by 1.3 kg with exenatide (difference between groups was 2.7 kg, p = 0.0001). Comparing to the control group, lower frequency of hypoglycemia as well as more gastrointestinal adverse events were in intervention group. Conclusions: Exenatide plus insulin glargine for 24 weeks resulted in significant reduction of albuminuria in T2DM patients with DKD.Trial registration: Clinicaltrials.gov, NCT02690883. Registered 20 February, 2016, https://clinicaltrials.gov/ct2/show/NCT02690883