Obesity and chronic kidney disease (CKD) are closely linked, and with the rapid uptake of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), nephrologists face practical questions about safety, treatment combinations, complications, and when to stop therapy. A session at American Society of Nephrology Kidney Week 2026 took on those questions and widened the lens to diet, physical activity, global access, and bariatric surgery.

“CKD and Obesity: GLP-1 Receptor Agonists and Other Management Strategies” was moderated by Alexander R. Chang, MD, MS, director of the Center for Kidney Health Research at Geisinger, and Meg Jardine, MBBS, PhD, director of the NHMRC Clinical Trials Centre at the University of Sydney, Australia.

Kidney Benefits Extend Beyond Weight Loss

Talat Alp Ikizler, MD, FASN, professor of medicine and director of the Division of Nephrology and Hypertension at Vanderbilt University Medical Center in Nashville, Tennessee, described obesity as a chronic, relapsing disease. Weight gain builds over years, and after weight loss the body responds with more hunger, less satiety, and lower energy expenditure, which typically leads to regain when treatment stops. GLP-1 RAs, with or without glucose-dependent insulinotropic polypeptide activity, work mainly by reducing appetite and food intake, he said, and their receptors in multiple organs produce effects beyond glucose control and weight loss.

In the phase 3 FLOW trial (NCT03819153), semaglutide (Ozempic; Novo Nordisk) 1 mg weekly lowered the risk of the primary kidney composite by 24% among 3533 adults with type 2 diabetes and CKD over a median 3.4 years (HR, 0.76; 95% CI, 0.66-0.88).¹ But weight loss was modest, 6.2% vs 1.6% with placebo, which Ikizler said shows the kidney benefit does not track with weight loss.

In an exploratory kidney analysis of SURPASS-CVOT (NCT04255433), which included 13,165 patients with type 2 diabetes and cardiovascular disease, tirzepatide (Mounjaro; Eli Lilly) lowered the risk of major kidney events by 23% vs the GLP-1 RA dulaglutide (HR, 0.77; 95% CI, 0.68-0.88).² The once-daily oral agent orforglipron (Foundayo; Eli Lilly) was noninferior to insulin glargine for cardiovascular safety in ACHIEVE-4 (NCT05803421) while lowering body weight an additional 8.9% vs glargine.³

For practice, Ikizler stressed an explicit plan for other medications when patients start on GLP-1 RAs. He also cautioned that weight loss includes lean tissue and that FLOW results should not be extrapolated to patients receiving dialysis or with a transplant.

Ikizler pointed to a randomized trial in which participants who exercised in tandem with liraglutide did best at keeping weight off.⁴ “The best exercise, as I always say, is the one that the patient can actually do,” he said.

One study found that among 151,649 people with type 2 diabetes starting dialysis, GLP-1 RA use was associated with a 23% lower risk of death (adjusted HR [aHR], 0.77; 95% CI, 0.70-0.85) and a 66% higher chance of transplant waitlisting (aHR, 1.66; 95% CI, 1.28-2.13), Ikizler said, highlighting that treatment with these drugs could help patients become eligible for transplant when they may not have been otherwise.⁵

Make Lifestyle Counseling Routine

Amy K. Mottl, MD, MPH, FASN, professor of medicine in the Division of Nephrology and Hypertension at the University of North Carolina at Chapel Hill School of Medicine, urged clinicians to talk with patients about excess weight and moving more without using the word “obesity” given the stigma around the condition.

“[GLP-1 RAs] are amazing; they’re probably the greatest medication for CKD that’s come along in 100 years,” Mottl said. “However, they alone will not be sufficient for patients.”

About 20 diet trials have enrolled only people with CKD, but all were small, so clinicians extrapolate from larger trials, Mottl explained. In the 2018 PREDIMED reanalysis of 7447 participants, a Mediterranean diet lowered the risk of myocardial infarction, stroke, or cardiovascular death (HR, 0.70; 95% CI, 0.55-0.89).⁶ In Look AHEAD, intensive lifestyle intervention produced 8.6% weight loss at 1 year vs 0.7% and later reduced progression to very-high-risk CKD (HR, 0.69; 95% CI, 0.55-0.87).^7,8

Mottl cited 2026 KDIGO Controversies targets: a 500 to 600 kcal daily deficit, though she starts at 250 to 500 kcal in her practice to ease patients into the lifestyle change; protein of 0.8 g/kg per day, or 1.0 to 1.2 g/kg on dialysis; 30 to 35 g of fiber; and building to 150 minutes of activity weekly with resistance exercise at least 2 days a week.⁹ Sarcopenic obesity affects up to 25% of people with CKD and may worsen with weight loss, making resistance exercise critical, Mottl noted. Before counseling, she said, it is crucial to ask about comorbidities, pain, binge eating, depression, food and housing insecurity, and whether a neighborhood is safe for walking.

For patients who cannot tolerate or access incretin-based drugs, she avoids orlistat, citing acute kidney injury and oxalate nephropathy, and said she has never prescribed naltrexone-bupropion (Contrave; Currax) because its metabolites accumulate as kidney function declines. Phentermine-topiramate (Qsymia; Vivus) is her second choice. It produced dose-dependent weight loss in a trial of 2487 adults, but Mottl noted it should be capped at 7.5 mg/46 mg when creatinine clearance falls below 50 mL/min and should be avoided in dialysis.¹⁰

“If you do not currently talk to patients about diet and exercise, you should definitely start doing that, and if you already do it, you should do it more frequently,” Mottl said.

Price, Not Efficacy, Limits Global Access

Ifeoma I. Ulasi, MBBS, MS, MSc, professor of nephrology at the College of Medicine, University of Nigeria, framed access around 5 dimensions: availability, accessibility, accommodation, affordability, and acceptability. Failure at any point can block real-world kidney benefit, she said, and vulnerable groups exist in every income setting—including migrants, refugees, uninsured patients, and rural communities in high-income countries. Access also begins before a prescription, with detecting and staging CKD, she noted.

Ulasi described a “double inequity.” High-burden populations are underrepresented in trials, and the same groups often have the least access to effective drugs. In a meta-analysis of 27 GLP-1 RA obesity trials, 84.2% of 1859 sites were in high-income countries.¹¹ The cheapest GLP-1 RA costs 1.6% of a minimum monthly wage in France vs 110.4% in Sri Lanka, she noted, and most treatment in Nigeria is paid out of pocket.¹² A preprint estimates generic semaglutide could be produced for $28 to $134 a year, Ulasi noted, which she called a reason for hope as patents expire.

Her recommendations for resource-constrained health systems included prioritizing patients with type 2 diabetes and CKD, pooled procurement of quality-assured generics as semaglutide patents expire, task sharing with primary care under specialist oversight, and trials that recruit in proportion to disease burden and plan for post-trial access.

“The question therefore is no longer whether therapies work,” Ulasi said. “It's about whether low-resource health systems can identify patients, finance, procure, deliver, and sustain treatment for those who are likely to benefit.”

Surgery Remains an Option for Selected Patients

Sankar D. Navaneethan, MD, MS, MPH, FASN, the Garabed Eknoyan MD Endowed Professor in Nephrology at Baylor College of Medicine and chief of the renal section at the Michael E. DeBakey VA Medical Center in Houston, Texas, said sleeve gastrectomy is now the most common bariatric procedure, with about 25% weight loss at 1 year vs 30% to 35% for Roux-en-Y gastric bypass.

In a matched cohort study led by Chang, the session’s moderator, surgery was associated with a lower risk of a greater than 30% estimated glomerular filtration rate decline (HR, 0.42; 95% CI, 0.32-0.55) and of doubling of serum creatinine or kidney failure (HR, 0.43; 95% CI, 0.26-0.71).¹³ In the Longitudinal Assessment of Bariatric Surgery-2 cohort of 2144 adults, KDIGO CKD risk categories improved after surgery for many patients at moderate or high baseline risk.¹⁴ Gastric bypass carries the higher risk of kidney stones and oxalate nephropathy, Navaneethan noted.

For sleeve gastrectomy, complication rates in patients with kidney failure were similar to those in patients without it (3.4% vs 3.6%), although readmissions were higher (8.6% vs 5.4%).¹⁵ Small studies suggest many selected patients on dialysis go on to transplant listing, and sleeve gastrectomy may be preferred for candidates to avoid malabsorption of immunosuppressants, Navaneethan said. Weight regain is common, with loss after sleeve gastrectomy falling from 25.2% at 1 year to 18.8% at 5 years.¹⁶ In a cohort of 208,155 patients who underwent bariatric surgery, adding tirzepatide after surgery yielded more weight loss than semaglutide (17.2% vs 12.0%).¹⁷

The session made the case that GLP-1 RAs are one part of managing obesity in CKD, not the sole answer. Lifestyle counseling, attention to lean mass during weight loss, and bariatric surgery for selected patients each have a role. As Ulasi emphasized, those benefits reach patients only if health systems can identify, finance, and deliver treatment to the people most likely to benefit.

References

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