Obesity Plus Heart Failure: What Are Safe and Effective Weight Loss Strategies?

Despite evidence that obesity and heart failure (HF) have multiple interactions, clinicians are often hesitant to broach the topic of weight loss with their patients. But evidence is now mounting on the clear benefits of weight loss for primary prevention of HF as well as for treatment of existing HF, particularly in those with preserved ejection fraction (HFpEF).

Two articles were recently published that review the data on different weight loss strategies with a focus on HF and provide guidance on implementing them. One, a JACC: Heart Failure State-of-the-Art Review (2024;12[9]:1509-1527), discusses the evidence for lifestyle changes, antiobesity medications and bariatric surgery. The second, published online in Circulation: Heart Failure, focuses more specifically on glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide/GLP-1 receptor agonists.

“We now have enough safety and efficacy data for weight loss therapies for heart failure patients with obesity to provide guidance on different strategies,” says Amanda Vest, MBBS, Section Head of Heart Failure and Transplantation Cardiology at Cleveland Clinic, who served as corresponding author of both reviews. “We urge our colleagues to help appropriate patients access strategies that can safely treat obesity.”

Weight loss – still a taboo subject?

Weight loss can safely help improve function and reduce HF hospitalization in patients with obesity and HF, yet many clinicians avoid the topic. Some are uncertain about the risks and benefits of weight loss strategies, especially as older antiobesity medications were associated with increased risk of elevated heart rate, blood pressure and even cardiovascular events.

Dr. Vest points out that obesity also carries a pervasive cultural stigma, leading even some clinicians to believe that patients could address the condition on their own if they were motivated to do so.

“We now know that the biological drive towards weight gain can be very strong, and for many patients, simply trying to practice dietary restriction is not an effective plan,” she says. “Fortunately, we now have strategies that do work well, and patients deserve the opportunity to benefit from them.”

Evidence for various obesity treatments — both in the prevention of HF and in patients with existing HF — is summarized in the figure below.

Strategy 1: Lifestyle

Successful diet and exercise programs can lower the risk of incident HF and safely help patients with existing HF lose weight. However, calorie restriction and increased exercise require intensive and sustained effort, and no single approach has been proven superior.

Strategy 2: Antiobesity medications

According to Dr. Vest, the advent of GLP-1 agonists has changed the landscape for addressing obesity. The large SELECT trial found that among patients with cardiovascular conditions and overweight or obesity, the combined incidence of cardiovascular death, myocardial infarction and stroke was reduced in patients taking once-weekly semaglutide (N Engl J Med. 2023;389[24]:2221-2232). Examining the subgroup of patients with HF at baseline showed a similar pattern of improved cardiovascular outcomes (Lancet. 2024;404:773-786).

Among patients with preexisting HF with preserved ejection fraction (HFpEF), the STEP-HFpEF trial found that those taking semaglutide successfully lost weight and achieved improved symptoms and functional capacity (N Engl J Med. 2023;389[12]:1069-1084). There was also a significant reduction in levels of the HF biomarker NT-proBNP and a reduction in diuretic requirements, suggesting improved HF stability for participants receiving semaglutide.

No large studies have yet been published on use of the new antiobesity medications in patients with HF with reduced ejection fraction (HFrEF), and safety concerns remain for some patients with advanced or unstable conditions.

“Results from heart failure subsets from other clinical trials also indicated potential benefits with GLP-1 receptor agonists in cardiorenal measures and long-term clinical outcomes,” says W. H. Wilson Tang, MD, Research Director, Section of Heart Failure and Transplantation Cardiology, who co-authored the JACC: Heart Failure review noted above. “Whether they have potential benefits in HFrEF is still debated, but we are gaining experience in using these new drugs in real-world clinical practice.”

Strategy 3: Bariatric surgery

Multiple retrospective cohort studies have indicated that surgical weight loss reduces future incident HF by about half. There are observational efficacy and safety data for patients with HF indicating reduction in mortality and HF hospitalizations. More prospective studies are needed that include patients with HF at baseline.

Guideline recommendations

Current standard clinical practice guidelines are as follows for patients with HF:

• Overweight (BMI 25-29.9 kg/m²): no evidence of benefit from weight loss, but a healthy lifestyle should be encouraged
• Obesity class I (BMI 30-34.9 kg/m²):
  –HFpEF: obesity treatment may help, especially with a GLP-1 agonist
  –HFrEF: the strategy should be based on HF stability, functional status, comorbidities and patient preference
• Obesity class II-III plus HF (BMI ≥ 35 kg/m²):
  –HFpEF: obesity treatment may help, especially with a GLP-1 agonist or bariatric surgery
  –HFrEF: although further study is needed, consider obesity treatment

Medication protocols in HF clinics

Dr. Vest pioneered antiobesity medication protocols for HF clinics, and she leads an active multidisciplinary program of this type at Cleveland Clinic. Patient eligibility includes those with clinically stable HF and class I obesity (with comorbidities or symptoms that would benefit from weight loss) or class II obesity.

Contraindications include a history of hypoglycemia, type 1 diabetes or pancreatitis, as well as a prior adverse reaction to a GLP-1 agonist. A personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome 2 is also disqualifying.

Patients must already be participating in an obesity management lifestyle program. “It's important to emphasize that antiobesity medical and surgical options should be offered in conjunction with intensive lifestyle interventions to achieve sustained weight loss as well as improved symptoms and outcomes,” says Dr. Tang. “This includes healthier dietary choices, regular physical activity, and strategies to enhance mental and emotional well-being.”

Before patients start a medication, HF stability must be determined and current medications reviewed for potential interactions (details on this and dosing schedules are provided in Dr. Vest’s review articles).

Patients with advanced HFrEF should be carefully monitored during drug initiation and up-titration, and evidence of HF decompensation or new ventricular arrhythmia should prompt immediate drug withdrawal and reconsideration of its use. Patients with type 2 diabetes should have blood glucose checked before and during initiating treatment and at each up-titration. All patients should have renal function and electrolytes checked about a month after starting treatment.

“Weight loss should be monitored, with a goal of at least 5% change by three months,” says Dr. Vest. “Ideally, the patient should have a multidisciplinary treatment team that includes a cardiologist, a pharmacist and a dietitian.”

What’s next, and remaining questions

Dr. Vest says she looks forward to publication of the results of the SUMMIT study, which evaluated tirzepatide, a combined GLP-1 and GIP agonist, in patients with HFpEF. And she recently had the opportunity to serve as the discussant for a study of a novel oral mitochondrial uncoupling agent called HU6 presented in the HUMAIN-HFpEF study at the Heart Failure Society of America annual meeting.

She notes that evidence is especially lacking for obesity treatment for patients with severe symptoms or with HFrEF.

“Are there subgroups of patients with HF in whom antiobesity medications may pose an unfavorable safety profile — or, conversely, may be especially helpful in reducing symptoms or risk?” she asks. “We need clinical trials to answer these important questions.”