Once-weekly exenatide did not significantly reduce unadjusted retinopathy or renal outcomes, including incident macroalbuminuria (2.2% vs 2.5% for placebo; HR 0.87; 95% CI 0.70-1.07).
RCT (n=13,844)
Does once-weekly exenatide improve microvascular and cardiovascular outcomes according to baseline renal function in participants in the EXSCEL trial?
Once-weekly exenatide did not significantly improve unadjusted renal or retinopathy outcomes, but modestly reduced cardiovascular risk in patients with eGFR ≥60 mL/min/1.73 m2.
Effect estimate: HR 0.87 (95% CI 0.70-1.07)
Absolute Event Rate: 2.2% vs 2.5%
OBJECTIVE To evaluate the impact of once-weekly exenatide (EQW) on microvascular and cardiovascular (CV) outcomes by baseline renal function in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL). RESEARCH DESIGN AND METHODS Least squares mean difference (LSMD) in estimated glomerular filtration rate (eGFR) from baseline between the EQW and placebo groups was calculated for 13,844 participants. Cox regression models were used to estimate effects by group on incident macroalbuminuria, retinopathy, and major adverse CV events (MACE). Interval-censored time-to-event models estimated effects on renal composite 1 (40% eGFR decline, renal replacement, or renal death) and renal composite 2 (composite 1 variables plus macroalbuminuria). RESULTS EQW did not change eGFR significantly (LSMD 0.21 mL/min/1.73 m2 95% CI −0.27 to 0.70). Macroalbuminuria occurred in 2.2% of patients in the EQW group and in 2.5% of those in the placebo group (hazard ratio HR 0.87 95% CI 0.70–1.07). Neither renal composite was reduced with EQW in unadjusted analyses, but renal composite 2 was reduced after adjustment (HR 0.85 95% CI 0.74–0.98). Retinopathy rates did not differ by treatment group or in the HbA1c-lowering or prior retinopathy subgroups. CV outcomes in those with eGFR 60 mL/min/1.73 m2 did not differ by group. Those with eGFR ≥60 mL/min/1.73 m2 had nominal risk reductions for MACE, all-cause mortality, and CV death, but interactions by renal function group were significant for only stroke (HR 0.74 95% CI 0.58–0.93; P for interaction = 0.035) and CV death (HR 1.08 95% CI 0.85–1.38; P for interaction = 0.031). CONCLUSIONS EQW had no impact on unadjusted retinopathy or renal outcomes. CV risk was modestly reduced only in those with eGFR ≥60 mL/min/1.73 m2 in analyses unadjusted for multiplicity.
Bethel et al. (Fri,) reported a rct. Exenatide vs. Placebo was evaluated on Incident macroalbuminuria (HR 0.87, 95% CI 0.70-1.07). Once-weekly exenatide did not significantly reduce unadjusted retinopathy or renal outcomes, including incident macroalbuminuria (2.2% vs 2.5% for placebo; HR 0.87; 95% CI 0.70-1.07).