Glucagon-like peptide 1 receptor agonist (GLP-1 RA): long-term effect on kidney function in patients with type 2 diabetes

Abstract Aims In a short-term study including 31 patients with type 2 diabetes, glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment was associated with a significant reversible decline in GFR. Twenty-three patients re-initiated GLP-1 RA treatment after the primary study, and the aim was to investigate the long-term effect on kidney function. Methods We included 30 patients in a one-year extension study, all initially treated with liraglutide for seven weeks. During follow-up 23 were treated with liraglutide and seven untreated. Primary outcome was change in GFR (51 Cr-EDTA plasma clearance). Results Patients were 61.5 (10.0) years and HbA1c 60.1 (13.8) mmol/mol. Baseline GFR was 100.6 (24.9) mL/min/1.73 m2 and was reduced by 11 (95% CI: 6.6–15.7, p < 0.001) mL/min/1.73 m2 , independent of change in 24-h systolic blood pressure (SBP), weight, UAER or HbA1c ( p ≥ 0.33). Geometric mean (IQR) of UAER was 25.5 (9.9–50.9) mg/d and was reduced by 27 (95% CI: 5–44; p = 0.020)%, and 24-h SBP was reduced by 8.2 ( p = 0.048) mmHg. No changes occurred in untreated patients. Conclusions Long-term treatment with liraglutide was associated with a reduction in measured GFR similar to the effect during short-term treatment, suggesting a metabolic or haemodynamic reversible effect and not structural changes. Moreover, UAER and 24-h SBP were reduced. Trial registration ClinicalTrials.gov identifier: NCT01499108.