Duration of diabetes and cardiorenal efficacy of liraglutide and semaglutide: A post hoc analysis of the LEADER and SUSTAIN 6 clinical trials

Abstract

Cardiovascular risk reduction with liraglutide and semaglutide in patients with type 2 diabetes was demonstrated in the LEADER (ClinicalTrials.gov: NCT01179048) and SUSTAIN 6 (ClinicalTrials.gov: NCT01720446) cardiovascular outcome trials. This post hoc analysis assessed the impact of diabetes duration (<5, 5 to <15, 15 to <25 and\u2009≥25\u2009years at baseline) on cardiorenal efficacy of these human glucagon‐like peptide‐1 analogues using a Cox proportional hazards model. Proportions of patients in the LEADER trial across diabetes duration strata were 15% (<5\u2009years, n\u2009=\u20091377), 50% (5 to <15\u2009years, n\u2009=\u20094692), 27% (15 to <25\u2009years, n\u2009=\u20092504) and 8% (≥25\u2009years, n\u2009=\u2009748); corresponding proportions in the SUSTAIN‐6 trial were 13% (<5\u2009years, n\u2009=\u2009422), 48% (5 to <15\u2009years, n\u2009=\u20091582), 30% (15 to <25\u2009years, n\u2009=\u2009977) and 10% (≥25\u2009years, n\u2009=\u2009316). Overall, longer diabetes duration was associated with higher age; higher prevalence of females; history of ischaemic stroke, peripheral arterial disease and insulin use; and inferior renal function. There was an increased frequency of major adverse cardiovascular events (MACE), expanded MACE and nephropathy events with increasing diabetes duration. Liraglutide and semaglutide consistently reduced the risk of cardiorenal outcomes across categories of diabetes duration (P‐interaction was not significant for all endpoints analysed).