Semaglutide reduces obesity-related MACE risk despite kidney impairment

medwireNews: Semaglutide is consistent at reducing the risk for major adverse cardiovascular events (MACE) in people with overweight or obesity regardless of kidney function impairment, report the SELECT trial investigators. Helen Colhoun (University of Edinburgh, UK) presented the prespecified analysis from the study showing that semaglutide efficacy was not impacted by estimated glomerular filtration rate (eGFR) nor urine albumin-to-creatinine ratio (UACR) at EASD 2024 in Madrid, Spain. She explained that the SELECT trial had previously demonstrated a 20% reduction in MACE for patients with pre-existing cardiovascular disease (CVD) and a BMI of 27 kg/m2 or above who were given semaglutide 2.4 mg/week versus placebo. The 17,604 trial participants were all aged at least 45 years, had a glycated hemoglobin level below 6.5% (48 mmol/mol), and were free from diabetes and end-stage renal disease. Overall, 11.1% of the 8803 patients randomly assigned to receive semaglutide had an eGFR rate of less than 60 mL/min per 1.73 m2, as did 10.7% of the 8801 patients who instead received placebo. The corresponding rates of microalbuminuria (30–299 mg/g) were 12.0% and 11.0%, and 1.9% of patients in both arms had macroalbuminuria (≥300 mg/g). MACE was defined as death from CV causes, or nonfatal myocardial infarction or stroke, and reported after a median 3.5 years of follow-up. Among patients with an eGFR below 60 mL/min per 1.73 m2, MACE occurred in 9.7% of those in the semaglutide arm and 13.5% of those in the placebo arm, giving a significant hazard ratio (HR) of 0.69. A similar pattern was observed for patients with an eGFR of 60 mL/min per 1.73 m2 or higher, for whom the rates of MACE were 6.0% and 7.3%, with a significant HR of 0.82. There was no significant difference in the benefit of semaglutide by eGFR. “This allows us to say that semaglutide was at least as effective in those with an eGFR below 60 [mL/min per 1.73 m2] at entry as in those with an eGFR above this,” Colhoun told delegates, adding that “semaglutide is almost halving the risk difference between people with and without an eGFR [below versus above] 60.” Similarly, the rates for MACE and any cause of death for participants with a reduced eGFR were 12.6% with semaglutide and 17.9% with placebo (HR=0.67), and for those without eGFR impairment, the rates were 7.5% and 9.0%, respectively, with a HR of 0.82. Again, no significant interaction was found between semaglutide benefit and eGFR status. Turning to the outcome by UACR, the presenter reported that MACE was slightly less common in semaglutide-treated patients than controls with a UACR of 30 mg/g or above (9.9 vs 12.3%, nonsignificant HR=0.80) and significantly less common in those with a UACR below 30 mg/g (5.9 vs 7.3%, HR=0.80). A similar pattern was also found when assessing MACE and any-cause death. “Semaglutide is approximately halving the risk difference between people with and without albuminuria in the trial,” commented Colhoun. The presenter said that the safety profile was “very reassuring,” noting that the adverse event rate was “similar” for patients given semaglutide and placebo, regardless of baseline eGFR status. Among patients with an eGFR below 60 mL/min per 1.73 m2, the rate of serious adverse events was slightly lower with semaglutide than placebo (36.6 vs 46.4%). The safety profile was also consistent between the treatment arms when assessing patients by baseline UACR, she continued, emphasizing that there was no evidence of an increase in acute renal failure events with semaglutide treatment. “Participants with reduced eGFR and/or albuminuria experienced a higher rate of MACE in SELECT compared with participants without these risk factors,” Colhoun summarized. Therefore, the absolute risk difference in MACE with semaglutide versus placebo is “greatest in those with reduced eGFR and/or albuminuria compared to those without,” she concluded. medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group EASD 2024; Madrid, Spain: 9–13 September

Keynote webinar | Spotlight on modern management of frailty

Springer Medicine

Semaglutide reduces obesity-related MACE risk despite kidney impairment

Related topics

EASD 2024

‘Noninferior’ reduction of type 1 diabetes HbA1c by weekly insulin efsitora alfa

Weight loss with new obesity drug amycretin

Tirzepatide significantly reduces UACR in individuals with obesity and type 2 diabetes

Liraglutide reduces BMI for young children with obesity

» View more highlights on the EASD 2024 hub page

At a glance: The STEP trials