The effect of liraglutide on renal function: A randomized clinical trial

Abstract

Aims: Among patients with type 2 diabetes and albuminuria, cardiorenal morbidity and mortality are high despite multifactorial treatment. Short-term reduction in albuminuria is considered suggestive of long-term renoprotective effects. We evaluated the renal effects of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide on top of multifactorial care, including renin-angiotensin-system (RAS)-inhibition.

Materials and methods: Randomized, double-blind, placebo-controlled, cross-over trial including patients with type 2 diabetes and persistent albuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² . Patients received liraglutide (1.8 mg/d) and matched placebo for 12 weeks in a random order. The primary endpoint was change in 24-h urinary albumin excretion rate (UAER).

Results: A total of 32 patients were randomized and 27 completed the study. After placebo treatment, geometric mean (IQR) UAER was 199 (81-531) mg/24-h, mean (SD) measured GFR (mGFR) 75 (36) mL/min/1.73 m² , 24-h blood pressure 145/80 (15/8) mm Hg and HbA1c 61 (11) mmol/mol. Liraglutide reduced HbA1c by 8 (95% CI: 5; 11) mmol/mol (P < .001) and weight by 1.8 (95% CI: 0.2; 3.4) kg (P = .032) compared to placebo. Furthermore, liraglutide reduced UAER by 32 (95% CI: 7; 50)% ( P = .017) compared with placebo. The change in mGFR was -5 (95% CI: -11; 2) mL/min/1.73 m² ( P = .15), and change in 24-h systolic blood pressure was -5 (95% CI: -10; 0) mm Hg ( P = .07). In multivariate regression models, change in UAER was associated with change in 24-h systolic blood pressure ( P = .025) but not with change in HbA1c, weight or mGFR ( P ≥ .14), overall model R ² = .39.

Conclusions: Our placebo-controlled randomized trial suggests that liraglutide has renoprotective effects on top of multifactorial treatment, including RAS-inhibition, in patients with type 2 diabetes and albuminuria.

Trial registration: ClinicalTrials.gov NCT02545738.

Keywords: GLP-1; diabetic nephropathy; liraglutide; randomized trial.