Effect of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on time to outcome in type 2 diabetes cardiorenal outcome trials

• Published in: Diabetes & metabolic syndrome clinical research & reviews Vol. 18; no. 2; p. 102945
• Main Authors: Rizzi, Alessandro, Kloecker, David E., Pitocco, Dario, Khunti, Kamlesh, Davies, Melanie J., Zaccardi, Francesco
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.02.2024
• Subjects: Cardiovascular Diseases; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Glucagon-Like Peptide-1 Receptor - agonists; Glucose; Humans; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
• ISSN: 1871-4021; 1878-0334; 1878-0334
• DOI: 10.1016/j.dsx.2024.102945

In randomized controlled trials (RCTs), treatment effects are commonly reported as hazard ratio, a measure often misinterpreted as a relative risk reduction. The acceleration factor (AF) indicates the extent to which a treatment increases/decreases the time before the occurrence of an outcome and gives useful insights in the interpretation of trials’ results. Using individual time-to-event data reconstructed from Kaplan-Meier plots, we estimated AFs for the primary outcomes (POs) and all-cause mortality in glucagon-like peptide-1 receptor agonists (GLP1-RAs) or sodium-glucose cotransporter-2 inhibitors (SGLT2-is) cardiorenal outcome trials in subjects with type 2 diabetes. AFs were estimated from 28 Kaplan-Meier plots of 19 RCTs. Compared to placebo, most GLP1-RAs increased the time before the onset of POs (from 9 % to 59 %) and all-cause mortality (from 8 to 13 %). Similarly, SGLT2-is increased time before the onset of POs (from 19 % to 87 %) and all-cause mortality (from 13 % to 42 %). The AFs provide a complementary and easier-to-interpret measure of treatment effect that could be useful to improve the shared decision-making. •The acceleration factor (AF) – how the time before an outcome is increased/decreased – can help interpret trial's result.•Using reconstructed time-to-event data, we estimated AFs for primary outcomes and death in GLP1-RAs and SGLT2-is trials.•AFs provide an easy-to-interpret measure of treatment effect, adding actionable information in clinical decision-making. SUMMARY In a randomised controlled trial, the acceleration factor (AF) indicates the extent to which the occurrence of an outcome is accelerated or delayed by an intervention, providing a complementary, easy-to-interpret measure of treatment effect. We estimated AFs for primary outcomes and all-cause mortality in type 2 diabetes cardiorenal outcome trials.