PHILADELPHIA (FRONTLINE MEDICAL NEWS) – Once-daily add-on liraglutide reduces HbA1c in patients with type 2 diabetes and moderate renal impairment when compared with placebo, according to findings from the phase III LIRA-RENAL trial.
The effects on blood glucose occurred across glomerular filtration rate (GFR) subgroups, and no worsening of kidney function occurred during the randomized, double-blind, 26-week study, Dr. David Scott reported at Kidney Week 2014.
In 277 patients with stage 3 chronic kidney disease (CKD) who were randomized to receive either an oral daily dose of 1.8 mg of liraglutide or placebo in addition to existing oral antidiabetic agents and/or insulin therapy, active treatment was associated with a significantly greater overall reduction in mean HbA1c from baseline to week 26 (–1.05% vs. –0.38%; estimated treatment difference, –0.66%). Similar reductions were seen in those with stage 3a disease (–1.10% vs. –0.35%; estimated treatment difference, –0.72%), and stage 3b disease (–0.97% vs. –0.40%; estimated treatment difference, –0.57%), Dr. Scott of Clinical Research Development Associates, Springfield Gardens, N.Y., reported at the meeting, which was sponsored by the American Society of Nephrology.
No significant treatment effect was observed on urinary albumin/creatinine ratio in any of the albuminuria subgroups. The estimated treatment ratios (liraglutide/placebo) were 1.09, 0.73, and 0.66 in those with normal (less than 30 mg/g), moderately increased (30-300 mg/g) or severely increased (greater than 300 mg/g) albuminuria levels.
Also, no difference was seen in estimated GFR change from baseline between the liraglutide and placebo groups (–1% vs. +1%, respectively), Dr. Scott said.
Adverse events and serious adverse events occurred in similar numbers of patients in the treatment and placebo groups (76% and 69%, and 10% and 11% of liraglutide and placebo patients, respectively), although those in the treatment group experienced more nausea and vomiting than did those in the placebo group (35.7% vs. 17.5%), he noted.
Confirmed hypoglycemia occurred in 11% and 17% of the liraglutide and placebo patients, respectively, but no real difference was seen between the groups with respect to severe hypoglycemia, he said.
Subjects were adults with body mass index of 20-45 kg/m2 and HbA1c of 7.0%-10.0%. All were on stable diabetes medication and had moderate renal impairment (estimated GFR of 30-59 mL/min/1.73 m2; modification of diet in renal disease).
“I think this is a very important study. It’s important, because as a clinical nephrologist, I’m faced day-to-day with the challenges of how to treat my diabetic patients with CKD. There are therapies that are contraindicated, there are therapies that are not well tolerated,” Dr. Scott said, explaining that treatment options remain limited for patients with diabetes and impaired renal function.
Further, while the incidence of diabetic nephropathy and diabetes has been declining, diabetes remains one of the most prevalent causes of CKD, and the incidence in some populations, including the elderly – who are at greatest risk for complications from therapy – has increased.
Although prior studies demonstrated that liraglutide was safe and well tolerated in patients with mild renal insufficiency, guidelines continue to include specific language suggesting that it is not indicated in the setting of CKD, Dr. Scott said.
The current findings provide additional evidence of the safety and efficacy of liraglutide in patients with type 2 diabetes and moderate renal impairment, he concluded.
The LIRA-RENAL trial was funded by Novo Nordisk. Dr. Scott reported having no disclosures.