Cardiovascular, kidney and safety outcomes with canagliflozin in older adults: A combined analysis from the CANVAS Program and CREDENCE trial

Aim: SGLT2 inhibitors may be underused in older adults with type 2 diabetes due to concerns about safety and tolerability. This pooled analysis of the CANVAS Program and CREDENCE trial examined the efficacy and safety of canagliflozin according to age. 

Methods: Pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401) were analysed by baseline age (<65 years, 65 to <75 years, and ≥75 years). A range of adjudicated clinical outcomes were assessed, including major adverse cardiovascular events and CKD progression, as well as safety outcomes. Cox proportional hazards models and Fine and Gray competing risk analysis were used. 

Results: Among the 14 543 participants, 7927 (54.5%) were <65 years, 5281 (36.3%) were 65 to <75 years and 1335 (9.2%) were ≥75 years. Older participants had higher rates of atherosclerotic cardiovascular disease and heart failure, longer diabetes duration and lower mean eGFR. Reductions in cardiovascular and kidney outcomes with canagliflozin were consistent across age categories (all p trend >0.10), although there was some evidence that effects on cardiovascular death and all-cause death were attenuated with older age (p trend = 0.02 and 0.03, respectively). Although the incidence of adverse events increased with age, effects of canagliflozin on safety outcomes including acute kidney injury, volume depletion, urinary tract infections and hypoglycaemia, were not modified by age (all p trend >0.10).

Conclusions: In patients with varying degrees of kidney function, canagliflozin reduced cardiovascular and kidney outcomes, regardless of age, with no additional safety concerns identified in older patients.