Long-term weight loss and cardiorenal outcomes by baseline BMI in the VERTIS CV trial

Diabetes Obes Metab. 2025 Feb;27(2):583-594. doi: 10.1111/dom.16050. Epub 2024 Dec 18.

Abstract

Aim: To assess weight loss and cardiorenal outcomes by baseline body mass index (BMI) in VERTIS CV.

Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. These post hoc analyses evaluated cardiometabolic and cardiorenal outcomes (a composite of death from CV causes or hospitalization for heart failure [HHF], CV death, HHF and an exploratory composite kidney outcome including ≥40% estimated glomerular filtration rate [eGFR] decrease) by baseline BMI, using conventional clinical categories and Cox proportional hazards models.

Results: In total, 8246 adults were randomized (mean age 64.4 years, diabetes duration 13.0 years, BMI 32.0 kg/m2, 61% with BMI >30 kg/m2). Absolute body weight reduction was greater with ertugliflozin versus placebo at 3 and 5 years in the overall population (p < 0.001) and across BMI subgroups. Ertugliflozin increased the proportion of participants achieving ≥5% and ≥10% body weight reduction (ertugliflozin 34.9% and 13.6%, placebo 19.4% and 4.1%; odds ratio [95% confident interval, CI], 2.21 [1.76-2.77] and 3.65 [2.39-5.57], respectively) at 5 years. No significant difference was observed in the effect of ertugliflozin on HHF across BMI subgroups (Pinteraction = 0.61). Similarly, no significant difference was observed in the effect of ertugliflozin on the kidney composite outcome across BMI subgroups (Pinteraction = 0.39). Results were similar for other CV outcomes, and safety was consistent with the known ertugliflozin profile.

Conclusion: Weight loss was observed across baseline BMI and was sustained over 5 years of follow-up. The effects of ertugliflozin on HHF and kidney composite were consistent across baseline BMI.

Keywords: body mass index; cardiovascular and kidney outcomes; ertugliflozin; metabolic outcomes; type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Atherosclerosis / epidemiology
  • Body Mass Index*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Double-Blind Method
  • Female
  • Heart* / drug effects
  • Humans
  • Kidney* / drug effects
  • Kidney* / pathology
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Treatment Outcome
  • Weight Loss* / drug effects

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • ertugliflozin
  • Sodium-Glucose Transporter 2 Inhibitors