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Liraglutide Reduces Albuminuria in Patients With Diabetes

Study finds treatment on top of stable renin angiotensin system (RAS)-inhibition decreased risk.

Adding liraglutide to standard-of-care (SOC) reduced the risk of nephropathy events, compared with placebo, among patients with type 2 diabetes. Patients with type 2 diabetes and albuminuria have high cardio-renal morbidity and mortality despite multifactorial treatment.

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial randomized patients with type 2 diabetes (hemoglobin A1C ≥7%) to receive liraglutide 1.8 mg/day or placebo for 12 weeks. After a 4-week washout, patients were then crossed-over and received liraglutide or placebo for another 4 weeks. A total of 27 patients completed the study.

The primary endpoint was change in 24-hour urinary albumin excretion rate (UAER).

All patients were age 50 years and older and had established cardiovascular (CV) disease or chronic renal failure; or were age 60 years and older and had risk factors for CV disease. The minimum duration of treatment was 3.5 years; the maximum duration was 5 years.

The primary endpoint of time to first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke occurred in 1,302 patients. The primary renal outcome (new onset of persistent macroalbuminuria; persistent doubling of serum creatinine; end-stage renal disease [ESRD]; or death due to renal disease) occurred in fewer participants treated with liraglutide (268 of 4,668) than with placebo (337 of 4,672)

This difference was primarily driven by new onset of persistent macroalbuminuria, occurring in fewer patients treated with liraglutide (161 of 4,668) than with placebo (215 of 4,672).

The authors wrote in their poster presentation. “Short-term reduction in albuminuria suggests long-term renoprotective effects.”

The study included 32 patients with type 2 diabetes and persistent microalbuminuria (urinary albumin-to-creatinine ratio >30 mg/g) and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.732.

The primary endpoint was change in 24-hour urinary albumin excretion rate (UAER).

Compared with placebo, liraglutide treatment reduced UAER by 26% (from 183 to 135; P = .022).

Liraglutide also reduced hemoglobin A1C (HbA1c) by 9 mmol/mol (from 63 to 53; P < .001) and weight by 1.8 kg (P = .032).

After placebo treatment, geometric mean (IQR) UAER was 199 mg/24-h (81-531), mean (SD) measured GFR (51Cr-EDTA) was 75 (36) mL/min per 1.73 m2, and Hb A1C was 61 (11) mmol/mol.

Change in UAER was associated with change in 24-hour systolic blood pressure, but not with change in HbA1C, weight or GFR. “Our placebo-controlled randomized trial suggests that liraglutide treatment has renoprotective effects on top of multifactorial treatment,” the authors concluded.

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,” said Bernt Johan von Scholten, MD, adding that, “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.

Practice Pearls:

  • Adding liraglutide treatment can reduce albuminuria by more than 30%.
  • A multivariate model found 24-hour systolic BP was associated with a reduced urinary albumin excretion rate.

References:

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]   [Presentation title: Renal Effects of Liraglutide in Type 2 Diabetic Patients With Albuminuria: a Randomized Clinical Trial. Abstract FR-PO815]