Effect of semaglutide on major adverse cardiovascular events by baseline kidney parameters in participants with type 2 diabetes and at high risk of cardiovascular disease: SUSTAIN 6 and PIONEER 6 post hoc pooled analysis

Abstract

Abstract Background Semaglutide is a glucose-lowering treatment for type 2 diabetes (T2D) with demonstrated cardiovascular benefits; semaglutide may also have kidney-protective effects. This post hoc analysis investigated the association between major adverse cardiovascular events (MACE) and baseline kidney parameters and whether the effect of semaglutide on MACE risk was impacted by baseline kidney parameters in people with T2D at high cardiovascular risk. Methods Participants from the SUSTAIN 6 and PIONEER 6 trials, receiving semaglutide or placebo, were categorised according to baseline kidney function (estimated glomerular filtration rate [eGFR] 300 versus 300 mg/g: 1.53 [1.14;2.04] and 2.52 [1.84;3.42]) had an increased MACE risk versus those without. Semaglutide consistently reduced MACE risk versus placebo across all eGFR and UACR subgroups (interaction p value [pINT] > 0.05). Semaglutide reduced HbA1c regardless of baseline eGFR and UACR (pINT>0.05); reductions in BW were affected by baseline eGFR (pINT0.05). More participants in the lower eGFR or higher UACR subgroups experienced SAEs versus participants in reference groups; the number of SAEs was similar between semaglutide and placebo arms in each subgroup. Conclusions MACE risk was greater for participants with kidney impairment or damage than for those without. Semaglutide consistently reduced MACE risk across eGFR and UACR subgroups, indicating that semaglutide provides cardiovascular benefits in people with T2D and at high cardiovascular risk across a broad spectrum of kidney function and damage. Trial registrations NCT01720446; NCT02692716.

Keywords

• Type 2 diabetes
• Cardiovascular disease
• Kidney disease
• Glucagon-like peptide-1 receptor agonist
• Semaglutide
• Major cardiovascular events