1 Year After CKD Approval, Semaglutide Transforms Diabetes, Kidney, and Heart Care

Just 1 year ago, semaglutide (Ozempic) was approved by the US Food and Drug Administration (FDA) for patients with chronic kidney disease (CKD) and type 2 diabetes (T2D).

This approval marked an important milestone as the first GLP-1 receptor agonist to reduce the risk of worsening kidney disease, kidney failure, and death due to cardiovascular disease in these patient populations.

What is a GLP-1?

Semaglutide, initially developed by Novo Nordisk, received its first approval from the FDA under the name Ozempic on December 5, 2017. Its first indication was as an injection of 0.5 mg or 1 mg once weekly for glycemic control in patients with type 2 diabetes (T2D) – as an adjunct to diet and exercise.1

Since then, semaglutide has exploded into nearly every related field. Glucagon-like peptide-1(GLP-1) receptors were discovered everywhere from the pancreas and the gastrointestinal tract to the heart, kidney, and liver. GLP-1 receptor agonists were quickly introduced into nephrology and cardiology, expanding their indications over the years to meet need in a variety of organs. Semaglutide has been at the forefront of this expansion due to its comparatively superior reductions of A1c, glucose, and overall weight.2

In 2020, semaglutide received approval for the reduction of cardiovascular risk in patients with T2D, marking its entry into the cardiology sphere. In January of 2025, semaglutide became the first GLP-1 receptor agonist approved for worsening kidney disease, kidney failure, and death due to cardiovascular disease in patients with T2D and chronic kidney disease (CKD). This approval marked semaglutide’s entry into the full cardio-kidney-metabolic (CKM) disease spectrum, addressing mortality and worsening outcomes for major contributing diseases.3,4

Now, just over a year after semaglutide’s approval for CKD, the editorial team at HCPLive has gathered insights from key clinicians across the CKM spectrum to discuss how this revolutionary drug overhauled the treatment landscape for kidney disease from all sides.

Revolutionizing Endocrinology

Semaglutide’s revolutionary impact on the endocrinology field cannot be understated. Despite not being the first, for years, this GLP-1 RA was the best method of reducing 3 major contributing factors to mortality in T2D. A1c reduction, glucose management, and weight loss saw substantial improvements as a result of the drug’s approval. However, semaglutide’s efficacy now extends far beyond T2D.

“I think that, sometimes, there’s hesitancy around starting a new therapy because the clinicians don’t know if other specialties will be on board,” Diana Isaacs, PharmD, the director of Education and Training in Diabetes Technology and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and a member of HCPLive’s advisory board, told HCPLive in an interview. “Now, we’re seeing through notes that nephrology is saying, ‘Why don’t you consider using semaglutide?’ And when they come to me as part of endocrinology, I see that, and I’m encouraged to use it. I think semaglutide really has enhanced team-based care in that we’re all on board.”

Isaacs went on to describe how semaglutide’s CKD approval provided a major paradigm shift for the American Diabetes Association’s standards of care.

“By showing its positive outcomes, particularly in people with kidney disease, semaglutide was paradigm-changing for the ADA Standards of Care and for our guidelines in that, previously, SGLT2 inhibitors were preferred for people with T2D and CKD,” Isaacs said. “Now, it’s either SGLT2 inhibitors or GLP-1 therapy – in practice, we’re now utilizing both of them.”

The Cardio-Kidney-Metabolic Landscape of Semaglutide

On October 9, 2023, the American Heart Association (AHA) released a presidential advisory regarding CKM syndrome, highlighting the interplay between metabolic risk factors, the cardiovascular system, and CKD. This syndrome has a significant impact on morbidity and mortality – poor CKM health, which is prominent among the American population, is associated with increased incidence of cardiovascular disease events.5

“CKM syndrome encompasses the entire spectrum of risk, starting from people who have no risk factors or cardiovascular disease, going all the way through obesity, vascular risk factors, subclinical disease, and clinical cardiovascular disease,” Janani Rangaswami, MD, professor of medicine at George Washington University and co-chair of the Scientific Advisory Group of the AHA’s presidential advisory on CKM Health, told HCPLive in an exclusive interview. “In any healthcare setting, the interplay between cardiology, nephrology, and endocrinology is the bulk of practice. In my practice, when I see individuals with kidney disease, diabetes alone is responsible for close to 50% of the cause of that kidney disease. When you add in obesity, metabolic dysfunction, and hypertension, all of these come together very heavily.”

Semaglutide’s approval for CKD effectively provided a bridge between all 3 specialties. When coupled with its initial diabetes indications and its cardioprotective effect, the drug was approved to tackle CKM syndrome on all fronts. Additionally, semaglutide’s efficacy when combined with SGLT2 inhibitors and RAAS blockade in patients with both CKD and high cardiovascular risk made it an effective tool for bolstering the protective effects of existing therapies. In this collaborative space between cardiology and nephrology, semaglutide became something of a miracle drug.

“While GLPs like semaglutide are very effective for A1c management and weight management, the FLOW trial really showed that this therapy saved lives, hearts, and kidneys,” Rangaswami said. “So now these therapies do multiple things; they’re addressing everything from improving lifespan to improving health outcomes, heart and kidney, and even beyond.”

The Bilateral Relationship Of CKD and Obesity

CKD remains one of the most common and serious complications of T2D, with obesity increasingly shaping disease trajectory, transplant eligibility, and therapeutic decision-making.6

As global rates of obesity and CKD continue to climb, clinicians are paying closer attention to how excess adiposity directly affects renal physiology, independent of diabetes and hypertension.6,7

“In obesity, metabolic demands increase, so the kidneys have to increase glomerular filtration rate and renal plasma flow to meet those demands. If nephron number is already reduced, the remaining nephrons have to work even harder. That leads to increased pressure inside each nephron, which causes barotrauma, scarring, and increased urine protein excretion,” explained Holly Kramer, MD, a nephrologist at Loyola University Medical Center and editor in chief of Advances in Kidney Disease and Health. “Severe obesity can also directly contribute to nephron loss through inflammatory effects. Often, obesity is accompanied by diabetes and hypertension, which further accelerate kidney disease progression.”

At BMI levels >40, systemic inflammation rises, adipokine signaling alters renal hemodynamics, and insulin resistance further increases glomerular stress. These processes frequently coexist with hypertension and T2D, amplifying cumulative kidney injury.8

Despite this convergence of risk factors, CKD is often managed reactively rather than proactively. By the time patients reach end-stage kidney disease (ESKD) and require maintenance dialysis, obesity can create additional barriers to transplantation because of higher perioperative and postoperative complication risks. Increasingly, clinicians are focused on intervening earlier in the disease course.6

The Potential of GLP-1 In CKD/T2D

In this landscape, GLP-1 agonists have emerged as a treatment strategy for patients with CKD and T2D, especially as a anti-imflammatory marker.

Subsequent research has shown an association of persistent low‑grade inflammation with worsened clinical outcomes in CKD, including faster eGFR decline, higher cardiovascular risk, and increased all‑cause mortality. Additionally, inflammation is a driving factor in the development and progression of T2D and its complications.

The reduction of inflammatory markers, such as CRP, has been highlighted as a potential clinical strategy to protect kidney function. In turn, semaglutide has been associated with reductions in CRP and other inflammatory markers independent of glycemic effects.9

“GLP-1 receptor agonists have become another pillar we can use for people with chronic kidney disease. I see them being used as an adjunct to other medications, such as SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. Especially when used in conjunction with those therapies, I think they have kidney benefits,” said Kramer. “They reduce urine albumin-to-creatinine ratios. If patients lose weight, we improve blood pressure control. If they have type 2 diabetes, glucose control improves. All of those factors help slow kidney disease progression, so I think GLP-1 receptor agonists are a great addition to our existing armamentarium.”

Where Obesity, CKD, and T2D Intersect with Semaglutide: The FLOW Trial

The approval for semaglutide for patients with T2D and CKD was based on data from FLOW, a phase 3b, multinational, parallel-group, double-blind, randomized, placebo-controlled trial investigating the effects of 1.0 mg once weekly semaglutide, a once-weekly GLP-1RA, on kidney outcomes in participants with CKD and T2D.4,10

“I think it has largely removed the uncertainty that once existed around the effects of GLP-1 receptor agonists on kidney function and has clearly demonstrated that these agents are kidney-protective,” FLOW study investigator, Vlado Perkovic, MBBS, PhD, and provost at the University of New South Wales, told HCPLive. “That, in turn, has informed guideline updates and helped the clinical community accept GLP-1 receptor agonists as a fourth pillar of care for people with diabetic kidney disease. That is a major advance.”

FLOW included 3533 participants with T2D and CKD, with the composite primary endpoint being time to first kidney failure, defined as persistent eGFR <15 ml/min/1.73 m2 or initiation of chronic kidney replacement therapy, persistent ≥50% reduction in eGFR, or death from kidney or cardiovascular causes.10

Over a median follow-up of 3.4 years, semaglutide reduced the risk of a primary outcome event by 24% compared with placebo (331 vs 410 first events; HR, 0.76; 95% CI, 0.66-0.88; P = .0003). Similar reductions were observed for the kidney-specific composite (HR, 0.79; 95% CI, 0.66-0.94) and cardiovascular death (HR, 0.71; 95% CI, 0.56-0.89).10

All confirmatory secondary outcomes favored semaglutide, including a slower annual decline in eGFR (difference, 1.16 mL/min/1.73 m²; P <.001), an 18% reduction in major cardiovascular events (HR, 0.82; 95% CI, 0.68-0.98; P = .029), and a 20% lower risk of all-cause mortality (HR, 0.80; 95% CI, 0.67-0.95; P = .01). Serious adverse events occurred in 49.6% of the semaglutide group versus 53.8% with placebo.10

Beyond Weight Loss: Inflammation and Future Directions of Semaglutide

Perkovic emphasized that FLOW was not intended to be a weight-loss trial, with a broad range of BMIs among participants, including 25% with BMI <27. While GLP-1 receptor agonists, especially semaglutide and emerging combination therapies, present efficacy regarding weight loss, FLOW indicated semaglutide’s specific kidney benefits not simply attributable to obesity treatment.10

However, Perkovic also remarked on patterns from the FLOW trial’s participant population, where the mean BMI was 32. Additionally, in the CREDENCE trial, which also evaluated patients with T2D and CKD, the mean BMI was 31. This highlights obesity as a prevalent, rather than incidental, comorbidity in contemporary CKD populations. Taken together, these findings underscore the importance of considering body weight as a core component of CKD risk assessment, rather than a secondary concern.10,11,12

“What that tells us is that people with diabetes and kidney disease are, on average, significantly overweight and often fall into the obese category. Many of these patients are therefore likely to benefit from weight loss as well,” explained Perkovic. “These therapies address multiple, parallel pathologies that commonly coexist in our patients, which makes them particularly exciting. It also raises the question of whether more potent agents that induce greater weight loss might confer additional kidney benefits, something that still needs to be tested.”

As obesity, T2D, and CKD increasingly converge in clinical practice, therapies capable of targeting overlapping metabolic, hemodynamic, and inflammatory pathways may redefine standard care. For clinicians managing complex kidney disease populations, GLP-1 receptor agonists now represent not simply a metabolic adjunct, but a foundational component of comprehensive CKD risk reduction.

Isaacs reports disclosures with Dexcom, Abbott, Lilly, Novo Nordisk, Medtronic, Insulet, and others.

Rangaswami reports relevant disclosures with the Veterans Health Administration, Boehringer Ingelheim, Bayer, Procyrion, and the American Heart Association.

Kramer reports relevant disclosures with Bayer, Alexion, American Journal of Kidney Disease, National Kidney Foundation, and others.

Perkovic reports relevant disclosures with AstraZeneca, Bayer, Boehringer Ingelheim, and others.

References

1. Novo Nordisk. Novo Nordisk Receives FDA Approval of OZEMPIC (semaglutide) Injection For the Treatment of Adults with Type 2 Diabetes. PRNewswire. December 5, 2017. Accessed February 19, 2026. https://www.prnewswire.com/news-releases/novo-nordisk-receives-fda-approval-of-ozempic-semaglutide-injection-for-the-treatment-of-adults-with-type-2-diabetes-300567052.html

2. Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019;10:155. Published 2019 Apr 12. doi:10.3389/fendo.2019.00155

3. Novo Nordisk. FDA approves Ozempic for cardiovascular risk reduction in adults with type 2 diabetes and known heart disease, updates Rybelsus label. PRNewswire. January 16, 2020. Accessed February 19, 2026. https://www.prnewswire.com/news-releases/fda-approves-ozempic-for-cardiovascular-risk-reduction-in-adults-with-type-2-diabetes-and-known-heart-disease-updates-rybelsus-label-300988672.html

4. Anderer S. FDA approves semaglutide to reduce risk of kidney disease progression. JAMA. 2025;333(13):1109. doi:10.1001/jama.2025.0548

5. Ndumele CE, Rangaswami J, Chow SL, et al. Cardiovascular-kidney-metabolic health: A presidential advisory from the American Heart Association. Circulation. 2023;148(20):1606-1635. doi:10.1161/cir.0000000000001184

6. Furth SL, Colhoun HM, Kanbay M, et al. The relationship between obesity and chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney international. Published online September 2025:S0085-2538(25)007744. doi:https://doi.org/10.1016/j.kint.2025.09.019

7. Good PI, Li L, Hurst HA, et al. Low nephron endowment increases susceptibility to renal stress and chronic kidney disease. JCI insight. 2023;8(3):e161316. doi:https://doi.org/10.1172/jci.insight.161316

8. Wang H, Fan K, Ning Y, et al. Hypertension and BMI as Mediators of Type 2 Diabetes-Induced CKD: Insights from an Integrative Multi-Database Study. Diabetes Metabolic Syndrome and Obesity. 2025;Volume 18:3343-3361. doi:https://doi.org/10.2147/dmso.s538554

9. Perkovic V. Inflammation Emerges as Promising CKD Treatment Target, With Vlado Perkovic, MBBS, PhD. HCPLive. Published February 9, 2026. Accessed February 20, 2026. https://www.hcplive.com/view/inflammation-emerges-as-promising-ckd-treatment-target

10. Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrology Dialysis Transplantation. 2023;38(9). doi:https://doi.org/10.1093/ndt/gfad009

11. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. New England Journal of Medicine. 2019;380(24):2295-2306. doi:https://doi.org/10.1056/nejmoa1811744

12. Pruijm M, Belmar N, Bjornstad P, et al. REMODELing mechanistic trials for kidney disease: a multimodal, tissue-centered approach to understand the renal mechanism of action of semaglutide. Kidney International. 2025;109(1):6-16. doi:https://doi.org/10.1016/j.kint.2025.10.005