Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial

Circulation. 2019 Jan 15;139(3):366-375. doi: 10.1161/CIRCULATIONAHA.118.038341.

Abstract

Background: Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61).

Methods: CAMELLIA-TIMI 61 randomly assigned 12 000 overweight or obese patients with or at high risk for atherosclerotic CV disease to lorcaserin or placebo on a background of lifestyle modification. The primary renal outcome was a composite of new or worsening persistent micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death.

Results: At baseline, 23.8% of patients had an estimated glomerular filtration rate (eGFR) <60 mL·min-1·1.73 m-2 and 19.0% had albuminuria (urinary albumin:creatinine ratio ≥30 mg/g). Lorcaserin reduced the risk of the primary renal composite outcome (4.2% per year versus 4.9% per year; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=0.0064). The benefit was consistent across subpopulations at increased baseline CV and renal risk. Lorcaserin improved both eGFR and urinary albumin:creatinune ratio within the first year after randomization. The effect of lorcaserin on weight, hemoglobin A1c, and systolic blood pressure was consistent regardless of baseline renal function. Likewise, there was no excess in cardiovascular events in patients assigned to lorcaserin in comparison with placebo, regardless of renal function. After adjustment for baseline characteristics, those with evidence of kidney disease were at increased risk of major CV events. Compared with patients with an eGFR ≥90 mL·min-1·1.73 m-2, those with an eGFR 60-90 and those <60 mL·min-1·1.73 m-2 had HRs of 1.25 (95% CI, 1.01, 1.56) and 1.51 (95% CI, 1.17, 1.95), respectively ( P for trend 0.0015). Likewise, compared with patients with no albuminuria (<30 mg/g), those microalbuminuria and those with macroalbuminuria had HRs of 1.46 (95% CI, 1.22, 1.74) and 2.10 (95% CI, 1.58, 2.80), respectively ( P for trend <0.0001).

Conclusions: Renal dysfunction was associated with increased CV risk in overweight and obese patients. When added to diet and lifestyle, lorcaserin reduced the rate of new-onset or progressive renal impairment in comparison with placebo.

Clinical trial registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02019264.

Keywords: albuminuria; kidney; obesity; serotonin receptor agonists.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Appetite Depressants / adverse effects
  • Appetite Depressants / therapeutic use*
  • Appetite Regulation / drug effects*
  • Benzazepines / adverse effects
  • Benzazepines / therapeutic use*
  • Biomarkers / blood
  • Blood Pressure / drug effects
  • Diet, Reducing
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Diseases / epidemiology*
  • Kidney Diseases / mortality
  • Kidney Diseases / physiopathology
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Obesity / mortality
  • Obesity / physiopathology
  • Obesity / psychology
  • Risk Assessment
  • Risk Factors
  • Risk Reduction Behavior
  • Serotonin 5-HT2 Receptor Agonists / adverse effects
  • Serotonin 5-HT2 Receptor Agonists / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Weight Loss / drug effects

Substances

  • Appetite Depressants
  • Benzazepines
  • Biomarkers
  • Glycated Hemoglobin A
  • Serotonin 5-HT2 Receptor Agonists
  • hemoglobin A1c protein, human
  • lorcaserin

Associated data

  • ClinicalTrials.gov/NCT02019264