Lorcaserin Cuts Risk of Obesity-Related Renal Dysfunction

Pam Harrison

November 13, 2018

CHICAGO — In addition to improving glycemic control in overweight and obese patients at high cardiovascular disease (CVD) risk, lorcaserin (Belviq, Eisai) improved established measures of renal function across all subpopulations studied in the CAMELLIA-TIMI 61 trial, new findings suggest.

The results were presented on November 11 here at the American Heart Association Scientific Sessions 2018 and simultaneously published in Circulation.

Given on a background of diet and exercise, lorcaserin reduced the primary renal composite endpoint by 13%, to 4.2% a year, compared with 4.9% per year for those taking placebo, at a hazard ratio (HR) of 0.87 (P = .0064), reported Benjamin Scirica, MD, MPH, Brigham and Women's Hospital, Boston, Massachusetts.

The primary renal composite outcome was defined as new or worsening micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, or any occurrence of end-stage renal disease, renal transplant, or renal death.

More specifically, active treatment lowered the risk of two components of the primary renal outcome, reducing new or worsening albuminuria to 2.7% compared with 3.1% for the control arm (P = .017), and reducing new or worsening renal function — assessed by estimated glomerular filtration rate (eGFR) or urine albumin-to-creatinine ratio (UACR) — to 2.4% compared with 2.9% for controls (P = .0018).

"Lorcaserin...is effective for weight loss, safe from a CV perspective, improves glycemic control including reducing the risk of developing diabetes and inducing remission of diabetes," Scirica and colleagues write in their new article.

"We now report that when added to lifestyle interventions, lorcaserin reduced the incidence and worsening of kidney disease in a large population of patients with established CVD, dysglycemia, and other CV risk factors."

"And the CV safety of lorcaserin was consistent across categories of baseline eGFR and UACR without any evidence for heterogeneity by renal function," they also note.

Lorcaserin Treatment Improved Renal Outcomes Across the Board

As previously described, the CAMELLIA-TIMI 61 trial involved 12,000 overweight and obese participants who had clinical evidence of CVD or multiple CVD risk factors, one of which could be type 2 diabetes.

In the overall cohort, 57% of patients already had type 2 diabetes on study entry and one third had prediabetes. Prediabetes was defined as an HbA1c of 5.7% to less than 6.5% or a fasting plasma glucose of 100 to 125 mg/dL.

At baseline, the median eGFR of the entire cohort was 76 mL/min/1.73 m2 and median baseline UACR was 7.0 mg/g.

At a median follow-up of 3.3 years, patients with higher baseline eGFR benefited less from lorcaserin than did those with lower baseline eGFR, the investigators note.

However, the benefit of active treatment on the primary renal outcome was similar in patients with and without diabetes, as well as in those with prediabetes.

Active treatment also improved both measures of renal function within the first year of study entry, improving mean eGFR by 1.2 mL/min/1.73 m2 and lowering mean UACR by 9 mg/g at 1 year, an effect that was sustained to study endpoint.

Safely Facilitating Weight Loss Cuts Obesity-Related Renal Dysfunction

The study authors note that the risk of sustaining primary major acute coronary events (MACE) was higher in patients with impaired renal function as measured by eGFR compared with those with normal renal function.

Patients with baseline macroalbuminuria were also at higher risk for sustaining a major CVD event during the study compared to those with only evidence of microalbuminuria.

"Lorcaserin, in addition to diet and lifestyle, reduced the rate of new onset or progressive renal impairment compared with placebo, regardless of baseline cardiometabolic risk," Scirica and colleagues conclude.

Regarding the clinical implications of the new findings, they say, "When contemplating weight-loss strategies, CV safety, improvement in glycemia, and prevention of the development or worsening of kidney disease should be considered."

But they also acknowledge, "Whether the improvements in renal function are related to weight-loss alone or any direct drug effect is not known; regardless of the mechanism of action, safely facilitating weight loss is likely the most important goal to minimize or improve obesity-related renal dysfunction."

The study was funded by Eisai. Scirica reports receiving grants from Eisai, AstraZeneca, Novartis, and Merck, and personal fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Eisai, Elsevier Practice Update Cardiology, GlaxoSmithKline, Merck, Novo Nordisk, and Sanofi.

Circulation. Published online November 11, 2018. Full text

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