The Expanding Frontier of Cardiometabolic Care

Am J Manag Care. 2026;32(Spec. No. 6):SP288-SP291. https://doi.org/10.37765/ajmc.2026.89971

Treating glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT2) inhibitors as single-indication drugs misses the full clinical and economic value of both drug classes, as the evidence mounts for benefits spanning liver disease, sleep apnea, stroke, heart failure, kidney injury, and obesity, according to presentations at a recent Institute for Value-Based Medicine event hosted by The American Journal of Managed Care in partnership with Optum and Kelsey-Seybold Clinic in Houston, Texas, on March 24, 2026.

Clinicians from cardiology, nephrology, hospital medicine, and obesity medicine gathered to examine how these 2 drug classes are reshaping cardiometabolic care—and how Kelsey-Seybold presents an example of an integrated health system putting that evidence into practice.

The Off-Target Revolution

The argument for GLP-1 receptor agonists and SGLT2 inhibitors has long rested on glucose lowering and, more recently, cardiovascular and renal protection. The evening’s opening presentation by Kenneth Cohen, MD, executive director of translational research at Optum Health, reframed both drug classes as transformative agents across an expanding set of disease domains. He highlighted the off-target benefits of these drugs that have recently come to light and challenged clinicians to stop thinking in silos when prescribing them.

Beginning with type 2 diabetes, Cohen outlined the benefits of driving toward remission, a concept that is underutilized in clinical conversations.

“We think a lot about treatment, but we don’t think about the fact that we can actually remit type 2 diabetes with effective weight loss,” he said.

Although the weight loss that comes with bariatric surgery can drive remission rates close to 90%, new drugs can also drive rates of remission greater than 70% with body weight loss of 30% or greater.¹ One of the benefits is that most patients with type 2 diabetes on multidose insulin can typically reduce the use of basal insulin when they take GLP-1s. This could allow patients to move from as many as 5 shots a day down to potentially 1 shot with less frequent glucose monitoring.

Focusing on liver disease, Cohen described a “burgeoning epidemic of cirrhosis” happening in the US. Models predict the incidence of metabolic dysfunction–associated steatohepatitis (MASH) to spike by 2050,² and Cohen emphasized that cirrhosis often results in liver transplants.

Currently, resmetirom (Rezdiffra) is the only approved therapy to treat MASH, formerly known as nonalcoholic steatohepatitis, or NASH,³ but research has shown the benefits of semaglutide.⁴ In a phase 3 trial, the GLP-1 showed a resolution of MASH without worsening of fibrosis in more than 60% of patients. A separate trial of tirzepatide showed similar results, with more than half of patients on the drug showing an improvement of at least 1 fibrosis stage without worsening of MASH.⁵

In the cardiovascular space, results from the SELECT trial (NCT03574597) has shown a 20% relative risk reduction in major adverse cardiovascular events (MACE) among patients with obesity without diabetes receiving semaglutide.⁶ However, Cohen noted that the absolute risk reduction was only 15%. At the current list prices, the cost per quality-adjusted life-year for MACE prevention alone is well above the accepted threshold for cost-effectiveness.

“Specifically for reduction in MACE, it’s hard to see a cost-effectiveness,” he said.

A meta-analysis found that SGLT2 inhibitors significantly outperformed GLP-1s in heart failure and renal outcomes.⁷ For heart failure with preserved ejection fraction (HFpEF), a study suggested that universal SGLT2 inhibitor use in the 2.6 million US patients with HFpEF could prevent roughly 250,000 hospitalizations over 3 years.⁸

In the sleep apnea space, tirzepatide led to a meaningful reduction in apnea-hypopnea index, with scores decreasing enough that patients could stop using continuous positive airway pressure therapy.⁹ Tirzepatide has been approved to treat moderate to severe sleep apnea in adults with obesity.¹⁰

Overall, an analysis of all the off-target benefits of GLP-1s shows that when the full portfolio of benefits is considered rather than a single indication, GLP-1s are considered cost-effective.¹¹

“We should not target specific indications for cost-effectiveness,” Cohen said. “More broadly, look at our patients and see how many of these off-target benefits would accrue to that individual patient. Do they have arthritis? Do they have sleep apnea? What is their cardiovascular risk? What is their liver risk? And as you begin to assemble these various comorbidities, all of which improve with the GLP-1 [receptor agonist], very quickly these drugs do become cost-effective.”

Treating the Disease, Not the Number: Obesity as a Chronic Condition

Following Cohen, Shawn Davis, MD, an obesity medicine specialist at Kelsey-Seybold, gave a presentation that situated GLP-1 receptor agonists within the full architecture of obesity treatment.

She emphasized that treatment should include patient-centered language and shared decision-making, and that the number on a scale is the least informative data point. There are 4 pillars of obesity treatment: nutrition therapy, physical therapy, behavioral modification, and medical interventions. When she sees a patient, her main goal is to decrease the burden of preventable chronic diseases.

“I explain to the patient, ‘I know you may be here because you want to see how you look in a bikini or whatever, but I really want you to live a long, healthy life,’” Davis said.

Davis discussed structuring treatment goals in a hierarchy that begins with the prevention of chronic disease, followed by functional improvement, and only then by weight loss.

On pharmacotherapy, Davis offered a full overview of the landscape, from phentermine, approved by the FDA in 1959 and still useful for cost-limited patients, to tirzepatide, which produces average weight loss approaching the efficacy of metabolic bariatric surgery but requires indefinite use to sustain benefit.

These medications are effective, but Davis emphasized that they must be used in conjunction with lifestyle changes, and they may need to be used long term.

“We hope to prove that treating obesity over the long term and remaining in adequate weight loss can actually decrease the total cost of care and dramatically improve a patient’s health span,” Davis said.

Shifting the Cardiac Imaging Paradigm With Coronary CT

Rohan Wagle, MD, a cardiologist at Kelsey-Seybold, presented the clinic’s experience transitioning from a nuclear stress test–dominant imaging program to one centered on coronary CT angiography (CCTA) to prevent, evaluate, and manage coronary artery disease. The change, according to Wagle, “injected value-based medicine into the work of coronary disease.”

At Kelsey-Seybold, nuclear stress testing yielded a false-positive rate of approximately 57%, with a positive predictive value of only 30%—meaning fewer than a third of patients sent for cardiac catheterization based on nuclear imaging actually required intervention. A CCTA-first strategy reduced the false-positive rate to 19% and increased the positive predictive value to 67%, resulting in a roughly 67% reduction in unnecessary invasive angiograms, Wagle explained.

The implementation relied on an e-consult system that routed primary care imaging orders through noninvasive cardiologists. Launched in July 2024, the program shifted the distribution of image-based stress testing ordered by primary care from nearly 100% nuclear to more than 50% CCTA within a year.

“When patients see their plaque, they cannot unsee it,” Wagle said, describing how visual evidence of coronary disease on CT drives medication adherence and lifestyle change in ways a normal stress test result never does. “It’s very powerful. They make tons of appointments. They always follow up. They have way more medication [adherence, and] they pay attention to their health more.”

Managing Acute Kidney Injury in the Clinic

The default assumption is that acute kidney injury (AKI) should be managed in the emergency department (ED), but Thai Dang, MD, a hospitalist at Kelsey-Seybold, challenged that assumption during his presentation.

“AKI can and should be managed in the clinic,” he said. “I’m not talking about your stage 3 AKI, but the [stage 1 and 2 cases]. We have an opportunity to change that curve on which patients go to the [ED].”

Kelsey-Seybold’s approach includes identifying at-risk patients, optimizing their volume status, stopping any medications that make kidney function worse, and dose-adjusting other medications. The clinic also utilizes nephrology e-consults and point-of-care ultrasound to keep appropriate patients out of the ED.

Heart Failure’s Silent Pandemic

Cardiologist Rupa Puttappa, MD, gave the evening’s final presentation with an examination of heart failure’s growing clinical and economic burden—and Kelsey-Seybold’s systematic response to it. With more than 8 million US adults predicted to have heart failure by 2030 and costs expected to exceed $70 billion,¹² she called heart failure “a silent global pandemic” that often goes undiagnosed until it lands patients in the ED.

Unfortunately, there are “significant gaps” when it comes to the use of guideline-directed medical therapy (GDMT), she said. For instance, fewer than 1 in 4 eligible patients with heart failure with reduced ejection fraction receive all 4 pillars of GDMT, Puttappa noted, despite evidence that doing so would reduce hospitalizations and progression of the disease.

At Kelsey-Seybold, the approach is a multimodal model of care that involves coordination among primary care, cardiology, nurses, and pharmacists. “We work as a team. Everyone addresses a certain area of this disease,” Puttappa said.

The result is that Kelsey-Seybold has improved adherence to the 4 pillars of GDMT by 12% across multiple disease states and populations, compared with what Puttappa described as single-digit or low-teen rates nationally.

Looking forward, Puttappa described the clinic’s deployment of artificial intelligence–assisted remote patient monitoring that tracks not just weight and blood pressure but heart rate variability, step counts, sleep cycles, and atrial fibrillation burden—aiming to intervene before fluid retention becomes visible on a scale.

REFERENCES

1. Kanbour S, Ageeb RA, Malik RA, Abu-Raddad LJ. Impact of bodyweight loss on type 2 diabetes remission: a systematic review and meta-regression analysis of randomised controlled trials. Lancet Diabetes Endocrinol. 2025;13(4):294-306. doi:10.1016/S2213-8587(24)00346-2
2. Le P, Tatar M, Dasarathy S, et al. Estimated burden of metabolic dysfunction–associated steatotic liver disease in US adults, 2020 to 2050. JAMA Netw Open. 2025;8(1):e2454707. doi:10.1001/jamanetworkopen.2024.54707
3. Joszt L. FDA approves resmetirom, first treatment for NASH with liver fibrosis. AJMC. March 14, 2024. Accessed May 5, 2026. https://www.ajmc.com/view/fda-approves-resmetirom-first-treatment-for-nash-with-liver-fibrosis
4. Sanyal AJ, Newsome PN, Kliers I, et al; ESSENCE Study Group. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392(21):2089-2099. doi:10.1056/NEJMoa2413258
5. Loomba R, Hartman ML, Lawitz EJ, et al; SYNERGY-NASH Investigators. Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391(4):299-310. doi:10.1056/NEJMoa2401943
6. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al; SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563
7. Alqurain AA, Salem M, Algarzai BA, et al. Comparative effectiveness of sodium-glucose cotransporter-2 (SGLT2) inhibitors versus glucagon-like peptide-1 (GLP-1) agonists on cardiovascular and renal outcomes in type 2 diabetes: a systematic review and network meta-analysis.
   Cureus. 2026;18(1):e100927. doi:10.7759/cureus.100927
8. Talha KM, Butler J, Greene SJ, et al. Population-level implications of sodium-glucose cotransporter-2 inhibitors for heart failure with preserved ejection fraction in the US. JAMA Cardiol. 2023;8(1):66-73. doi:10.1001/jamacardio.2022.4348
9. Malhotra A, Grunstein RR, Fietze I, et al; SURMOUNT-OSA Investigators. Tirzepatide for the treatment of obstructive sleep apnea and obesity. N Engl J Med. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881
10. Joszt L. Weight loss drug tirzepatide now approved for sleep apnea in adults with obesity. AJMC. December 20, 2024. Accessed May 5, 2026. https://www.ajmc.com/view/weight-loss-drug-tirzepatide-now-approved-for-sleep-apnea-in-adults-with-obesity
11. Lin GA, Le W, Fahim SM, et al. Semaglutide and Tirzepatide for Obesity: Effectiveness and Value; Final Report. Institute for Clinical and Economic Review. December 16, 2025. Accessed May 6, 2026. https://icer.org/wp-content/uploads/2025/12/ICER_Obesity_Final-Report_For-Publication_121625.pdf
12. Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail. 2013;6(3):606-619. doi:10.1161/HHF.0b013e318291329a