For type 2 diabetes patients with persistent albuminuria, adding liraglutide, a glucagon-like peptide-1 receptor agonist, to treatment with renin-angiotensin system (RAS) inhibitors may result in a clinically meaningful reduction in 24-hour urinary albumin excretion rate (UAER).
In a 12-week double-blind, cross-over trial (ClinicalTrials.gov, NCT02545738), 27 patients with a urinary albumin-to-creatinine ratio (UAER) above 30 mg/g and estimated glomerular filtration rate (eGFR) above 30 mL/min/1.73 m2 were randomly assigned to liraglutide (1.8 mg daily) or placebo, with a 4-week washout period in between.
After placebo treatment, the geometric mean UAER was 199 mg/24 hours, measured GFR was 75 mL/min/1.73m2, 24-hour blood pressure (BP) was 145/80 mmHg, and hemoglobin A1c (HbA1c) was 61 mmoL/moL, according to results published online ahead of print in Diabetes Obesity and Metabolism. Liraglutide compared with placebo cut HbA1c by 8 mmoL/moL and weight by 1.8 kg over 12 weeks. Liraglutide was associated with a 32% reduction in UAER. The change in mGFR was -5 mL/min/1.73m2 and was likely temporary. Change in 24-hour systolic BP was -5 mmHg. A multivariate model found 24-hour systolic BP was associated with UAER. The investigators found no significant differences in levels of RAS hormones between liraglutide and placebo.
“By demonstrating liraglutide treatment to reduce albuminuria by more than 30%, we suggest liraglutide as a novel treatment option with the capability to lower albuminuria on top of existing RAS-inhibition in patients with persistent albuminuria,” Bernt Johan von Scholten, MD, of Steno Diabetes Center Niels Steensens in Gentofte Denmark, told Renal & Urology News. “Liraglutide might therefore be renoprotective and prevent progression of diabetic kidney disease.”
The effects may be attributable to decreases in BP, HbA1c, and plasma levels of renin concentration and angiotensin II.
Large-scale studies examining the long-term effects of liraglutide and comparable glucose-lowering drugs on progression in diabetic nephropathy are needed. Almost half of patients reported adverse events, with 5 patients discontinuing the drug due to nausea, vomiting, or diarrhea.
The study was funded by Novo Nordisk, the makers of Victoza and Saxenda (liraglutide) a financial supporter of the Steno Diabetes Center, where several study authors are employed.
1. 1. von Scholten BJ, Persson F, Rosenlund S, Hovind P, Faber J, Hansen TW, and Rossing P. The effect of liraglutide on renal function: A randomised clinical trial. Diabetes Obes Metab. 2016 Oct 17. doi: 10.1111/dom.12808. [Epub ahead of print]