Counting days: Cardiovascular and kidney event postponement with glucagon‐like peptide 1 receptor agonists in individuals with type 2 diabetes

Glucagon-like peptide 1 receptor agonists (GLP-1RA) with ≥24-h pharmacodynamic activity delay the development and progression of cardiovascular and kidney disease in individuals with type 2 diabetes, and the benefits are consistent across subcutaneous and oral formulations, as recently demonstrated in a systematic review and meta-analysis of 10 large, randomized controlled trial.1 Specifically, GLP-1RA reduced the incidence rate of major adverse cardiovascular events (MACE), defined as first occurrence of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke, by 14% (hazard ratio 0.86 [95% CI 0.81, 0.90]) with a number needed to treat (NNT) of 63 based on a weighted average median trial follow-up of 3.2 years. As with any other medication, even when prescribed according to guidelines, the person with diabetes receiving a GLP-1RA should be adequately informed about the benefits and risks of the therapy. However, although relative risks and NNT are statistically meaningful, they remain challenging for many people to interpret in a personal context. An alternative, potentially more intuitive measure that has been suggested is the postponement of outcomes.2, 3 The concept aligns with the underlying physiology: GLP-1RA therapy does not confer absolute protection against cardiovascular and kidney events, but slows disease progression, thereby delaying the onset of critical endpoints.4 However, outcome postponement estimates have not been widely adopted, perhaps because the underlying calculations are complex or time-consuming. To investigate the postponement of cardiovascular and kidney events in individuals with type 2 diabetes treated with GLP-1RA, we extracted the following data from the 10 trials that were included in the recently published systematic review and meta-analysis (LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, REWIND, PIONEER 6, AMPLITUDE-O, FREEDOM-CVO, FLOW, SOUL): (1) study duration, (2) mortality rate in the placebo group, and (3) hazard ratio for MACE and its individual components, a composite kidney outcome (kidney failure [kidney replacement therapy or persistent estimated glomerular filtration rate