GLP-1 RAs Tied to Lower Kidney Failure Risk in Patients With Obesity, CKD

Adults with chronic kidney disease (CKD) and obesity who did not have diabetes had a lower 5-year risk of end-stage kidney outcomes when treated with a glucagon-like peptide-1 receptor agonist (GLP-1 RA), according to a retrospective real-world study being presented at the American Society of Nephrology’s Kidney Week 2026 in Denver, Colorado. With GLP-1 RAs now widely used for weight management, the findings suggest that a prescription filled for obesity may carry kidney and cardiovascular implications pharmacists should keep in view, although the observational design cannot establish cause and effect.¹

Nadim Ojaimi, MD, a nephrology fellow at the University of Maryland Medical Center who conducted the study with his mentor, Valeriu Cebotaru, MD, emphasized in a comment to Pharmacy Times that “the findings are associations, not causal effects.”

Nearly 35,000 Matched Patients per Group

The investigators used the TriNetX Research Network, which included electronic health record data from 112 health care organizations, to identify adults 18 years and older with CKD and obesity without diabetes. The exposed cohort included patients treated with semaglutide (Ozempic, Wegovy; Novo Nordisk), dulaglutide (Trulicity; Eli Lilly), liraglutide (Victoza, Saxenda; Novo Nordisk), tirzepatide (Zepbound, Mounjaro; Eli Lilly), lixisenatide (Adlyxin, Lyxumia; Sanofi), or exenatide (Byetta; AstraZeneca). Controls were adults with CKD and overweight or obesity without diabetes who had an outpatient encounter and no GLP-1 RA exposure.¹

Propensity score matching accounted for demographics, heart failure, hyperlipidemia, and baseline medication use, including angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, yielding 34,980 patients in each cohort. The primary outcome was a composite of end-stage renal disease, dialysis, or kidney transplantation.¹

Over 5 years, the primary composite outcome occurred in approximately 3.3% of patients treated with GLP-1 RAs versus 6.0% of controls (HR, 0.513; 95% CI, 0.477-0.551; P < .001). Mortality rates were 1.6% vs 5.8% (HR, 0.251; 95% CI, 0.229-0.276), respectively, and heart failure exacerbation occurred in 15.5% vs 19.1% (HR, 0.744; 95% CI, 0.718-0.772). Both secondary outcomes were considered significant at P < .001.¹

Ojaimi said the death and kidney failure associations should be interpreted with caution. “Both are far larger than in SELECT (NCT03574597) and FLOW (NCT03819153; about 20%), so they are best read as a signal, not a true effect size,” he said.

The heart failure finding is more credible, he noted. “That more modest effect is closer to what trials in obesity-related heart failure have shown, such as SELECT (NCT03574597) and SUMMIT (NCT04847557) with tirzepatide, which makes it more plausible than the mortality estimate.”

Consistent With Trial Data, But Key Details Are Missing

In a prespecified analysis of the SELECT trial, which enrolled patients with overweight or obesity and established cardiovascular disease without diabetes, once-weekly semaglutide 2.4 mg lowered the incidence of a composite kidney endpoint vs placebo (1.8% vs 2.2%; HR, 0.78; 95% CI, 0.63-0.96; P = .02).²

In patients with type 2 diabetes and CKD, the FLOW trial found that semaglutide 1.0 mg weekly reduced the risk of major kidney disease events by 24% compared with placebo (HR, 0.76; 95% CI, 0.66-0.88).³

The abstract does not report CKD stage, baseline estimated glomerular filtration rate (eGFR), albuminuria, which agents or doses patients received, or how long they stayed on therapy.¹

"Likely contributors to the larger effects include healthy-user bias and confounding by frailty and access to care," Ojaimi said. "We also did not match on CKD stage, eGFR, albuminuria, or SGLT2 inhibitor use." He added that electronic health record data have limits of their own, including variable coding and missed deaths outside the network, and that the team could not assess weight change.

What Pharmacists Should Watch

"In nondiabetic CKD, GLP-1 RAs are used to treat weight or cardiovascular risk, and they are not yet a proven kidney therapy," Ojaimi said. "No renal dose adjustment is needed, though exenatide should be avoided below an eGFR of 30."

Drug interactions and volume status also matter. "[Gastrointestinal] losses combined with diuretics, RAAS blockers, SGLT2 inhibitors, or nonsteroidal anti-inflammatory drugs raise AKI risk, so titrate slowly and teach sick-day rules," he said.

For monitoring, a prespecified analysis of the SMART trial (NCT04889183)—which enrolled 101 adults with CKD and overweight or obesity without type 2 diabetes—found that changes in lean body mass and fat mass during 24 weeks of semaglutide 2.4 mg weekly did not correlate with changes in creatinine- or cystatin C–based eGFR or measured GFR. The investigators said this suggests weight reductions of about 10% do not influence GFR estimates.⁴

Ojaimi still recommended a cautious approach. "Muscle loss can overstate eGFR, so consider cystatin C and watch protein intake and sarcopenia," he said.

Looking ahead, Ojaimi said the key trial would test whether GLP-1 RAs reduce hard kidney outcomes and death in patients with obesity and CKD without diabetes when added to RAAS blockade and SGLT2 inhibitors and whether any benefit holds independent of weight loss.

REFERENCES

1. Ojaimi N, Cebotaru V. GLP-1 receptor agonists (RAs) use and kidney and cardiovascular outcomes in adults with CKD and obesity without diabetes: a retrospective real-world study. Abstract presented at: ASN Kidney Week 2026; October 24, 2026. Abstract SA-PO0412.

2. Colhoun HM, Lingvay I, Brown PM, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058-2066. doi:10.1038/s41591-024-03015-5

3. Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109-121. doi:10.1056/NEJMoa2403347

4. Heerspink HJL, Soler M, Beernink JM, et al. Effects of semaglutide on body composition and GFR: a prespecified analysis of the SMART trial. Clin J Am Soc Nephrol. 2026;21(7):1149-1158. doi:10.2215/CJN.0000001051