Liraglutide with Moderate Renal Impairment

The glucagon-like peptide (GLP)-1 receptor agonist liraglutide in combination with other glucose-lowering drugs was an effective treatment for patients with inadequately controlled type 2 diabetes and moderate renal impairment, according to the results of the phase III LIRA-RENAL trial published recently in Diabetes Care.

“Few clinical trials have reported results with a GLP-1 receptor agonist in patients with type 2 diabetes and moderate renal impairment,” wrote researcher Melanie J. Davies, of the Diabetes Research Centre at the University of Leicester, United Kingdom, and colleagues. “Liraglutide did not affect renal function and demonstrated better glycemic control and weight reduction, with no increase in hypoglycemia.”

However, the researchers also pointed out the use of liraglutide resulted in a higher number of withdrawals due to gastrointestinal adverse events when compared with placebo.

The trial was a 26-week, double blind trial that included 279 patients with inadequately controlled diabetes. Patients also had moderate renal impairment defined as an estimated glomerular filtration rate (eGFR) of 30 to 59 mL/min/1.73 m². All patients were randomly assigned to once-daily liraglutide 1.8 mg (n=140) or placebo (n=139).

At 26 weeks, patients assigned to liraglutide had a mean reduction in HbA1c of -1.05% compared with -0.38% for patients assigned placebo. This was an estimated treatment difference of -0.66% in favor of liraglutide (P<0.0001). There was also a greater decrease in fasting plasma glucose seen in patients assigned liraglutide compared with placebo (-1.22 mmol/L vs. -0.57 mmol/L; P=0.0036).

Although patients in both groups experienced some weight loss during the trial, patients assigned liraglutide had significantly more weight loss than patients assigned placebo. At 26 weeks the average weight loss for liraglutide was -2.41 kg compared with -1.09 kg for placebo (P=0.0052). Treatment with liraglutide also resulted in a reduction in body mass index compared with placebo (-0.88 kg/m² vs. -0.38 kg/m²).

The researchers found that treatment with liraglutide did not affect the eGFR.

“It is of clinical relevance that there was no worsening of renal function in patients treated with liraglutide while on diverse background glucose lowering therapy,” the researchers wrote. “Treatment differences were not observed in the week 26 ratio to baseline for eGFR. The observed urine-to-creatinine ratio as an indication of a patient’s albuminuria was 17% lower with liraglutide, although not statistically significant.”

Patients assigned liraglutide did experience a higher rate of gastrointestinal side effects compared with patients assigned placebo (35.7% vs. 17.5%). However, treatment with liraglutide was not associated with any increase in hypoglycemic episodes.

“The high withdrawal rate (~25%) in both treatment groups is a limitation of this trial,” the researchers wrote. “This trial investigated an older and frailer population, which might lead to more adverse events, specifically GI effects, being experienced by the patients. Several post hoc sensitivity analyses, conducted due to concerns about missing data, supported the conclusions of the primary statistical method.”

Davies MJ, et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): a randomized clinical trial. Diabetes Care. Epub 2015 Dec 17.