Background: Limited understanding exists regarding phenotypic heterogeneity in type 2 diabetes (T2D) patients and its therapeutic impact.
Methods: A pooled latent class analysis of the CANVAS Program and CREDENCE trial was conducted to identify T2D clinical phenotypes. The composite outcome of cardiovascular death (CVD) or hospitalization for heart failure (HHF) was analyzed and proportional hazards models assessed the effect of canagliflozin across phenotypes.
Results: Four phenotypes were identified: Phenotype 1 (n=966, 6.6%) with the lowest prevalence of heart failure, kidney dysfunction, and hypertension; Phenotype 2 (n=4169, 28.7%), primarily females with high atherosclerotic cardiovascular disease (ASCVD) prevalence; Phenotype 3 (n=7108, 48.9%), predominately men with high ASCVD prevalence; and Phenotype 4 (n=2300, 15.8%) with the highest prevalence of heart failure and renal dysfunction. Differential risk for CVD or HHF across phenotypes was observed, with the lowest risk in Phenotype 1 and the highest risk in Phenotype 4 (HR 5.21 [95% CI: 3.69-7.36]; Fig 1A and B). Canagliflozin significantly reduced CVD or HHF across phenotypes (P-interaction > 0.05).
Conclusion: This study identified four distinct T2D phenotypes with differential CV risk. Canagliflozin significantly reduced the risk of CVD or HHF across phenotypes.
A. Razaghizad: None. J. Ni: None. E. Possik: None. M. Tsoukas: Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Boehringer-Ingelheim, Janssen Pharmaceuticals, Inc., AstraZeneca, Sanofi, Bausch Health, Abbott. T.A. Mavrakanas: Research Support; AstraZeneca. Other Relationship; AstraZeneca, Janssen Pharmaceuticals, Inc., Pfizer Inc. Advisory Panel; Bayer Inc. Other Relationship; Bayer Inc. Advisory Panel; Servier Laboratories. Other Relationship; Boehringer-Ingelheim. Advisory Panel; Boehringer-Ingelheim, GlaxoSmithKline plc. T. Huynh: Research Support; Pfizer Inc., Merck & Co., Inc., Bayer Inc. Speaker's Bureau; GlaxoSmithKline plc. W. Swardfager: None. P. Marques: Other Relationship; Janssen Pharmaceuticals, Inc. A. Sharma: Other Relationship; Boehringer-Ingelheim. Research Support; Janssen Pharmaceuticals, Inc. Other Relationship; Novo Nordisk. Advisory Panel; Novartis Canada. Other Relationship; AstraZeneca. Advisory Panel; Servier Laboratories, Takeda Pharmaceutical Company Limited. Research Support; Boston Scientific Corporation, Medtronic, Amgen Inc.
