Managing Cardio-Renal-Metabolic Diseases Requires Multifactorial Approach

Cardio-renal-metabolic diseases affect multiple aspects of health, with heart failure, obesity, and chronic kidney disease (CKD) among the chief concerns in cardio-renal-metabolic health. The Institute for Value-Based Medicine^® (IVBM) event held in Nyack, New York, on September 18, 2025, took the time to focus on each of these health conditions, offering potential means of treating and managing each, including through the use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) for obesity management and the management of heart failure by primary care physicians.

GLP-1 RAs Are Helpful in Obesity Management, Have Off-Target Benefits

GLP-1 RAs have been the subject of discussion in the medical field for the past several years, with new studies demonstrating the benefits of the treatment in diabetes, obesity, and cardiovascular management, among other applications. Speakers at the IVBM event encouraged the use of GLP-1s and sodium-glucose cotransporter 2 (SGLT2) inhibitors for both obesity management and off-target areas of concern.

Scott T. Hines, MD, chief quality officer and medical director at Crystal Run Healthcare, opened his presentation by talking about the role of GLP-1 RAs in obesity management. “GLP-1 [RAs] are the most powerful medications currently available to treat obesity and many of its comorbidities,” he said.

Obesity, he said, is controlled by the hormone leptin, which is released when eating so that the body feels full. However, the levels of leptin released go down when there is a loss in weight. GLP-1, as a hormone, also works to increase satiety, making individuals feel full, which is produced in lower amounts when an individual loses weight. This, he said, is why most individuals maintain only 3 kg of weight loss after 4 and a half years.

Patients often do not establish a formal weight loss plan with their primary care physician, which is then followed up on by that physician. Some patients do not bring up their weight due to embarrassment, and a majority of physicians also avoid bringing it up due to embarrassment themselves.

Semaglutide and tirzepatide are 2 GLP-1s that have come into use in recent years. Semaglutide is capable of helping patients lose up to 15% of their total body weight, with 86% losing at least 5% of their body weight.¹ Tirzepatide results in a mean weight loss of 21%, with 91% of patients losing at least 5% of their body weight.²

“I think we can agree that the GLP-1s are pretty advantageous for weight loss, but many times what prevents these are [adverse] effects,” Hines said.

He emphasized that keeping patients on a consistent dose, and not necessarily the highest dose, is the goal. When patients experience adverse events, it’s easier to reduce the dose rather than increase it, even though some patients may request a higher dose when they perceive their hunger increasing.

“You don’t have to stop. You can cut back and see if they can tolerate a lower dose. Or the other option is just to use a much slower titration schedule,” Hines explained.

Gastrointestinal adverse events can be mitigated by adjusting the dosage or by prioritizing diet quality. Avoiding high-fat foods, carbonated beverages, and alcohol can help alleviate these symptoms. Doctors should be aware of quick weight loss because it could lead to gallstones or could be a sign of worse conditions hiding below the surface. Hines also stated that, due to the expense of the medication, methods such as weaning to the lowest effective dose may help maintain weight loss while also allowing the patient to afford it.

The off-target benefits of GLP-1 RAs and SGLT2 inhibitors were a topic of conversation during a talk presented by Ken Cohen, MD, executive director of translational research at Optum Health. Cohen stated that he wanted to focus on the benefits of GLP-1 RAs and SGLT2 inhibitors beyond their use in treating obesity and diabetes alone.

“For these studies, virtually all of these studies have been published in the last year or two, so the volume of literature and the speed with which it’s being published are just astounding,” Cohen said.

He highlighted a study published in Lancet Diabetes & Endocrinology³ that found patients could achieve remission of diabetes through weight loss, with a remission rate up to 90% depending on the percentage of body weight lost. Liver fibrosis is also an area that can be benefited through GLP-1 RAs. Patients treated with semaglutide were found to have 50% greater resolution of fibrosis and twice the resolution of metabolic dysfunction–associated steatohepatitis.⁴

Cohen also highlighted the SELECT trial,⁵ whose results were published in the New England Journal of Medicine in 2023 and showed that an obese, nondiabetic population had cardiovascular benefits from receiving semaglutide.

“Keep in mind, this is a secondary prevention trial and most of the benefit was driven by reduction in nonfatal myocardial infarction,” he said. “The absolute risk reduction, which wasn’t reported on that slide, was only 1.5%…[which is] different than the 20% that’s reported.”

Cohen explained that using GLP-1 RAs solely to reduce major adverse cardiovascular events would likely not be cost-effective; however, they are cost-effective when used for multiple indications.

“At the end of the day, these drugs are cost-effective. And it’s important because the cost of the GLP-1 [RAs] continues to be something that you deal with every day.… Overall, the drugs are cost-effective based on the sum total of all benefits that they bring to our patients,” Cohen concluded.

Heart Failure, CKD Are Areas of Concern for Cardio-Renal-Metabolic Diseases

Outside obesity and weight management, other presentations focused on CKD and heart failure aspects of cardiorenal metabolic diseases. Rafeel Syed, MD, an internal medicine and nephrology specialist at Crystal Run Healthcare, expressed his enthusiasm about discussing CKD.

“When I was asked to present today about [CKD], I was actually quite excited because in the last 2 to 3 years, a lot has changed in the world of nephrology,” he said.

Syed reviewed the current state of CKD management and the evolution of treatment for the condition. More than 35 million individuals live with CKD, according to Syed, with 28% of the Medicare budget spent on CKD in 2013. CKD can increase the risk of adverse outcomes like all-cause mortality and cardiovascular mortality, and it is projected to be the fifth leading cause of death by 2040.

When patients are referred to nephrologists, the nephrologist can assess the cause of CKD, measure the glomerular filtration rate (GFR) and the albumin in urine, and look at the complications of CKD that can affect the patient, such as elevated blood pressure, anemia, and malnutrition.

Until recently, Syed said, there had been no major breakthroughs for nephrologists to treat CKD. Now, there are 4 pillars to consider. The oldest, angiotensin-converting enzyme (ACE) inhibitors, are now joined by SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists (MRAs), and GLP-1 RAs.

The use of SGLT2 inhibitors for CKD is supported by trial results that showed a 50% or more decline in GFR, end-stage kidney disease, or death from any renal or cardiovascular outcomes.⁶ “The trial was stopped and SGLT2 inhibitors became a very important tool in the management of CKD,” said Syed.

MRAs have been tested alongside SGLT2 inhibitors as a combination treatment and shown to result in a 50% reduction in proteinuria. SGLT2 inhibitors, by themselves, have been used to control magnesium and hematopoiesis. GLP-1 RAs showed a decline of more than 50% in renal and cardiovascular death when 1 mg was given once per week subcutaneously.

“If you look at data from some single-agent trials, the lifetime benefit from combination therapy of these drugs is a 3.2-year free survival for cardiovascular events, 5 and a half years for CKD progression, and a 2 and half year [survival] for all-cause mortality,” Syed explained.

Syed also emphasized that he recommends exercise, smoking cessation, and limiting alcohol to all of his nephrology patients, alongside these treatments, to give patients a well-rounded treatment plan.

Steven M. Goldberg, MD, FACC, FACP, the chair of the Department of Cardiology at Optum Health, also touched on heart failure. He explained the Agewise program, which uses electronic health records in the office to ask screening questions for early detection of chronic diseases. Heart failure has high incidence and mortality rates; Goldberg explained that patients with heart failure face a 50% mortality rate within a year. Patients older than 60 years are the targeted population for the Agewise screening.

“For the most part, there’ll be a questionnaire that the patients will hopefully fill out at home that may come electronically into the computer, and that will be asking patients…Have you noticed a change in endurance, vague shortness of breath…with day-to-day activities? Is there a change in shortness of breath…and if that pro-BNP [pro–B-type natriuretic peptide] is above a certain level, that will allow us to order an echocardiogram to try to find left ventricular dysfunction before it’s clinically evident,” Goldberg explained.

The questionnaire enables doctors to address heart failure as early as possible, helping patients reduce their risk of worse outcomes. SGLT2 inhibitors, ACE inhibitors, MRAs, and diuretics are first-line treatments for heart failure according to clinical guidelines. There are also ongoing clinical trials that are testing methods for preventing heart failure, including methods to prevent heart attacks, through lipid management.

The IVBM event covered a variety of means of addressing cardio-renal-metabolic diseases, highlighting GLP-1 RAs and SGLT2 inhibitors as first-line treatments for several conditions. These new methods of treatment have transformed the space, enabling doctors to prescribe effective therapies that target the root causes of cardio-renal-metabolic diseases.

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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