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

Subodh Verma, Stephen C Bain, Tea Monk Fries, C David Mazer, Michael A Nauck, Richard E Pratley, Søren Rasmussen, Hans A Saevereid, Bernard Zinman, John B Buse, Subodh Verma, Stephen C Bain, Tea Monk Fries, C David Mazer, Michael A Nauck, Richard E Pratley, Søren Rasmussen, Hans A Saevereid, Bernard Zinman, John B Buse

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 ≥25 years 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 years, n = 1377), 50% (5 to <15 years, n = 4692), 27% (15 to <25 years, n = 2504) and 8% (≥25 years, n = 748); corresponding proportions in the SUSTAIN-6 trial were 13% (<5 years, n = 422), 48% (5 to <15 years, n = 1582), 30% (15 to <25 years, n = 977) and 10% (≥25 years, n = 316). 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).

Keywords: LEADER; SUSTAIN 6; cardiorenal; cardiovascular; diabetes duration; efficacy; liraglutide; renal; semaglutide.

Conflict of interest statement

Author contributions

Statistical analyses were performed by Søren Rasmussen, and Subodh Verma prepared the first draft. All authors were responsible for the content and editorial decisions, were involved at all stages of manuscript development and approved the final version.

Patient level analysis data sets for the research presented in the publication are available from the corresponding author upon request.

© 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Risk of cardiorenal events in patients treated with liraglutide (upper panel) or semaglutide (lower panel) vs placebo, by diabetes duration at baseline. LEADER total population: 9340. LEADER total population with diabetes duration available: 9321. SUSTAIN 6 total population (all patients with diabetes duration available): 3297. MACE comprised CV death, nonfatal MI and nonfatal stroke. Expanded MACE comprised MACE components plus coronary revascularization and hospitalization for unstable angina or heart failure. Nephropathy events were defined as new onset of macroalbuminuria or doubling of serum creatinine level and eGFR ≤45 mL/min/1.73 m2, the need for continuous renal‐replacement therapy or death from renal disease. Abbreviations: CI, confidence interval; CV, cardiovascular; eGFR, estimated glomerular filtration rate; GLP‐1, glucagon‐like peptide‐1; MACE, major adverse cardiovascular events; N, number of patients with event; R, events per 100 patient years of observation

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