Mitigating Cardiometabolic Risk Through Therapies, Weight Management

Am J Manag Care. 2025;31(Spec. No. 10):SP733-SP736. https://doi.org/10.37765/ajmc.2025.89801

Weight management and available therapies in the cardiometabolic space were among the topics discussed during the Institute for Value-Based Medicine (IVBM) event held August 19, 2025, in Aurora, Colorado, where experts examined various means of managing cardiometabolic risk in patients. The speakers delivered presentations on different aspects of cardiometabolic risk and how to address the complications surrounding heart health.

“I’m so excited for the program tonight to talk about the exploding field of cardiometabolic disease,” Marc Bonaca, MD, MPH, FAHA, FACC, executive director of the Colorado Prevention Center and director of vascular research and professor of medicine at the University of Colorado (CU) Anschutz Medical Campus in Aurora, said as he introduced the event. “This is a field that is growing. It’s a wonderful opportunity for our patients, but there are a lot of challenges that we have to deal with.”

Weight Management Is Key to Managing Cardiometabolic Care

Weight management plays a key role in cardiometabolic prevention due to obesity’s link to worsened outcomes in cardiovascular health. Several discussions during the IVBM event centered on ways clinicians can support their patients in losing weight to improve their health, ranging from drug interventions to surgeries.

Josephine Harrington, MD, an assistant professor at CU Anschutz, highlighted how obesity is a risk factor for heart failure with preserved ejection fraction (HFpEF). She shared data with the audience showing the association between body mass index (BMI) and the risk of developing HFpEF. “You can see that as patients develop more severe obesity, as their BMI goes up, they have an absolutely linear increase in their risk of developing HFpEF,” she said.

Not only is obesity linked to HFpEF, but people who are overweight can also experience sleep apnea. Stephen Duntley, MD, a neurologist at UCHealth and professor of clinical practice at CU Anschutz, discussed the link between sleep apnea and obesity, stating that “40% to 70% of [patients with obesity] have obstructive sleep apnea.”

Sleep apnea, he said, can affect all aspects of metabolic syndrome. “We have reduced sleep, and that causes increased inflammation.… There’s sympathetic activation, initially only at night, but it begins to occur throughout the daytime and has adverse effects on multiple systems,” Duntley explained.

With all these adverse consequences of overweight and obesity, interventions and treatment options are needed to address the issue nationwide. One potential intervention to mitigate weight as a risk factor is the PATHWEIGH process, introduced by Leigh Perreault, MD, FACE, FACP, an endocrinologist and associate professor of medicine at CU Anschutz. Perreault emphasized that population-level weight gain is estimated at 0.5 kg per year, without any strategy to change this trend worldwide. Any developed strategy, she said, would have to
be sustainable, which PATHWEIGH aims to be.

“[PATHWEIGH is] not a weight loss program.… People love to say it’s a weight loss program. It’s not. It’s a process of care for patients to receive medical assistance with their weight in primary care on a long-term basis,” Perreault said.

The strategy has been pilot tested in 2 studies, after which it was deployed across the UCHealth system. Patients can make a weight-prioritized visit if they would like medical assistance with their weight, and they fill out an intake questionnaire before the visit. The questionnaire includes questions about the goals they would like to achieve in their weight management. During the visit, clinicians can discuss these goals with patients and develop strategies that can be accessed via the patient portal.

Patients who received weight-related care through this intervention lost 1.73 kg more than those who only received weight-related care during primary care and 2.37 kg more than people who never received an intervention for weight loss. “Unfortunately, of all the patients receiving weight-related care, only 4%
actually used those [electronic health record] tools that I was talking about. So, clearly, we have some work to do,” Perreault said.

Bariatric surgery was also discussed during the IVBM event, with Jason Tibbels, MD, chief medical officer of Lantern, examining the surgery’s role in an era of weight-loss therapies such as semaglutide. Lantern is a platform that connects health plans and employers with top providers who provide high-cost procedures.

“If you look at the title of my talk, you might expect my next slide to just be blank, and I’ll just go sit back down,” Tibbels joked as he began his presentation, titled “What Is the Role of Bariatric Surgery in the Era of Incretin-Based Therapies?”

He noted that the indications for bariatric surgery and glucagon-like peptide-1 (GLP-1) receptor agonists are often similar and cross over, which makes appropriate advising in patients important. The number of bariatric surgeries performed per year has declined, with a study conducted by researchers at Brigham and Women’s Hospital in Boston, Massachusetts, showing a decrease of 8.7% from 2022 to 2023.¹ Obesity, Tibbels said, is being managed increasingly through medication, but bariatric surgery remains a well-established and effective tool in weight loss.

“It’s not uncommon to see bariatric [surgery] weight loss of 30% at 1 year and a lot of durability such that 25% maintained [their weight loss] at 10 years,” Tibbels said. “I’m putting that next to what I think is probably the most effective GLP-1 receptor agonist today, tirzepatide, where you see 22% weight loss, and then just pointing out when people do stop, [they see] 50% weight gain at a year.”

Although adverse events can lead to individuals stopping their use of GLP-1 receptor agonists, the most common reasons are likely cost and access, Tibbels said. Also, bariatric surgery has been shown to add approximately 2.3 more quality-adjusted life-years compared with GLP-1 receptor agonists. Instead of looking to choose between them, though, Tibbels suggested that there could be a means of combining these approaches to achieve the best results—for example, offering bariatric surgery to those who cannot afford GLP-1 agents and have no comorbidities vs offering a stepwise approach to using GLP-1 drugs in patients with multiple comorbidities and keeping bariatric surgery as an option for the future.

“Again, there are no head-to-head comparative data on which approach is best, and I think my theory is there’s a role for both, and it is on us to sort out what that approach is,” Tibbels concluded.

Therapies, Medications Remain an Avenue for Preventing Cardiometabolic Events

The panel not only focused on addressing weight loss in patients to diminish their risk of cardiometabolic diseases but also went over therapies and drugs to mitigate cardiometabolic events. GLP-1 receptor agonists were a major focus as a method of reducing such events. Although the class of drug is well known for its use in diabetes and weight loss, study findings have shown a key association between GLP-1 receptor agonists and the reduction of cardiovascular events.² This makes it an interesting avenue for future treatment of cardiometabolic conditions.

Fatima Rodriguez, MD, MPH, associate professor of medicine at Stanford University in California, began her presentation by emphasizing that 80% of heart disease cases are preventable, even as deaths related to cardiovascular problems have risen. High cholesterol, physical inactivity, diabetes, and cigarette smoking are all modifiable risk factors. Rates of obesity and overweight prevalence are high in the US, at 42% and 31%, respectively, and excess weight is “directly linked to hypertension, coronary artery disease, stroke, and heart failure,” Rodriguez said. As such, treating cardiovascular disease requires treating these comorbidities as well.

GLP-1 receptor agonists, Rodriguez said, are generating excitement. She noted, however, that some of these agents did not yet have evidence of working to reduce cardiovascular risk in those without diabetes. “Even though these trials are upcoming, there is no trial that shows that tirzepatide can be used in adults without diabetes, just for obesity, for the purpose of cardiovascular risk reduction,” Rodriguez said. Bariatric surgery is still needed to supplement these medications, she added.

In contrast, semaglutide has seen promising results in trials. Rodriguez went over results of the phase 3 SELECT trial (NCT03574597),² which changed the game in cardiovascular spaces. The patients in SELECT represented a secondary prevention population, as they had cardiovascular disease with obesity and no diabetes and received a dose of semaglutide of 2.4 mg. Major adverse cardiovascular events were reduced by 20% in this population. Both the oral and injectable versions of semaglutide displayed these results. When it comes to recommending medication, Rodriguez said that tirzepatide is more effective in weight loss compared with semaglutide, so knowing what a patient needs is important.

GLP-1 receptor agonists were also highlighted in other presentations, and experts praised the promising results from early studies. “I don’t want to say everything’s coming up roses, but there’s a lot of positive that’s been seen with these GLP-1 drugs,” Joseph Saseen, PharmD, BCPS, BCACP, CLS, a clinical pharmacist and professor at CU Anschutz, said.

Saseen also discussed new methods of treating kidney disease, which is heavily tied to cardiometabolic prevention. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and GLP-1 receptor agonists have both shown favorable outcomes for kidney health in the long term, he said. Drugs targeting liver function are also gaining ground in the space, as liver function ties into the overall condition.

Cecilia Low Wang, MD, a professor of endocrinology at CU Anschutz, concurred that addressing cardiovascular-kidney-metabolic (CKM) syndrome—which connects heart disease, kidney disease, diabetes, and obesity under one name—is vital to prevent cardiometabolic risk. Across 15 years, stage 4 CKM has a 9.6% increased absolute mortality risk vs stage 0, she said, making it a valid syndrome.³ Triple combination therapy of SGLT2 inhibitors, GLP-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists has shown some benefit in reducing negative clinical outcomes, but more research is needed, Low Wang said.

“We need more evidence, grade 1A evidence, for combination therapy. We need to figure out how to do this in a cost-effective way and target the right patients, and then we also need to improve access,” Low Wang explained.

More research is also needed on encouraging adherence to GLP-1 drugs in the real world, according to Jacinda Nicklas, MD, MPH, MA, a primary care physician and associate professor at CU Anschutz.

“When we think about GLP-1s, 6% of US adults are currently using them,” Nicklas said. “About 12% say they use it now or they’ve used it in the past.”

However, Nicklas noted that 85% of those who use GLP-1 drugs stop after 2 years. “Those of us who are practicing know there are a lot of factors for this.… It’s mostly insurance coverage and cost of these medications, and most patients can’t stay on them long term,” she said.

GLP-1 agents are a promising avenue, Nicklas concluded, but adherence is still the most significant challenge moving forward as clinicians plan to prescribe the treatment more often for those with overweight or to reduce the incidence of cardiovascular events.

As described in the speakers’ presentations, clinicians have the means to prevent cardiometabolic conditions from worsening. Interventions encouraging weight loss to improve overall health, including use of the GLP-1 drugs that are transforming the cardiometabolic space, can not only spur weight loss but also improve outcomes in cardiovascular, kidney, and liver diseases. Continued research is needed to translate these interventions and treatments into real-world population-level outcomes.

Author Information: Ms Bonavitacola is an employee of MJH Life Sciences, the parent company of the publisher of Population Health, Equity & Outcomes.

REFERENCES

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2. 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
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   incidence of mortality associated with cardiovascular-kidney-
   metabolic (CKM) syndrome. J Am Soc Nephrol. 2025;36(7):1343-1351. doi:10.1681/ASN.0000000637