Can a 56-year-old man with hypertrophic obstructive cardiomyopathy and obesity be treated with a glucagon-like peptide‑1 receptor agonist for weight loss?

Can a 56-year-old man with HOCM and obesity be treated with GLP-1 receptor agonists for weight loss?

Yes, GLP-1 receptor agonists can be used for obesity treatment in this patient with hypertrophic obstructive cardiomyopathy (HOCM), and emerging evidence suggests they may actually improve cardiovascular outcomes in this specific population.

Primary Recommendation Based on Most Recent Evidence

A groundbreaking 2025 real-world study of 29,521 patients with hypertrophic cardiomyopathy (HCM) demonstrated that GLP-1 receptor agonists in patients with obesity and HCM were associated with significantly lower all-cause mortality and heart failure hospitalization rates over 2 years, with no increase in arrhythmias or safety concerns 1. This is the highest quality and most recent evidence directly addressing your question, and it strongly supports the use of GLP-1 receptor agonists in this exact patient population.

Evidence-Based Treatment Algorithm

Step 1: Confirm Eligibility

• BMI criteria: This patient qualifies if BMI ≥30 kg/m² (obesity alone) or BMI ≥27 kg/m² with weight-related comorbidities 2
• Screen for absolute contraindications: Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN2) 2, 3
• Cardiac assessment: The presence of HOCM is NOT a contraindication; in fact, recent evidence suggests benefit 1

Step 2: Pre-Treatment Cardiac Evaluation

• Document HCM phenotype: Assess current symptoms, NYHA class, and recent echocardiographic findings 4
• Screen for heart failure: While GLP-1 receptor agonists show benefit in HFpEF, caution is warranted in HFrEF 4
• Baseline natriuretic peptides: Consider BNP or NT-proBNP to establish baseline cardiac status 4
• Arrhythmia history: Document any history of atrial fibrillation or ventricular arrhythmias, though the 2025 study showed no increased arrhythmia risk with GLP-1 receptor agonists 1

Step 3: Medication Selection

For this patient with HOCM and obesity, prioritize:

1. Semaglutide 2.4 mg weekly (Wegovy) - First choice

   • Achieves 14.9% weight loss at 68 weeks 2, 3
   • Proven 20% reduction in cardiovascular death, nonfatal MI, or stroke in patients with established CVD 2
   • The 2025 HCM study included patients on various GLP-1 receptor agonists with favorable outcomes 1

2. Tirzepatide 15 mg weekly (Zepbound) - Alternative for maximum weight loss

   • Superior weight loss of 20.9% at 72 weeks 2, 3
   • Broader cardiometabolic benefits including blood pressure reduction 3
   • No specific HCM data yet, but mechanism suggests benefit 5

Step 4: Initiation Protocol

Semaglutide titration schedule:

• Week 1-4: 0.25 mg weekly 3
• Week 5-8: 0.5 mg weekly 3
• Week 9-12: 1.0 mg weekly 3
• Week 13-16: 1.7 mg weekly 3
• Week 17+: 2.4 mg weekly (maintenance) 3

Critical monitoring during titration:

• Assess every 4 weeks for gastrointestinal tolerance, weight loss progress, and blood pressure 3
• Monitor for signs of heart failure decompensation (increased dyspnea, edema, weight gain) 4
• Check blood pressure regularly as weight loss may necessitate adjustment of antihypertensive medications 2

Cardiovascular Benefits Specific to HOCM

The 2025 propensity-matched study of 1,497 patients with HCM and obesity on GLP-1 receptor agonists versus 1,497 matched controls demonstrated:

• Significant reduction in all-cause mortality 1
• Lower heart failure hospitalization rates 1
• No increase in atrial fibrillation or ventricular arrhythmias 1
• Significant BMI reduction over 2-year follow-up 1

These findings are particularly important because obesity in HCM patients is associated with:

• More severe phenotype 1
• Worse clinical outcomes 1
• Increased cardiovascular risk 1

Mechanisms Supporting Use in HOCM

• Weight loss reduces cardiac workload: Significant weight reduction decreases left ventricular mass and improves diastolic function 5
• Blood pressure reduction: GLP-1 receptor agonists lower both systolic and diastolic blood pressure, beneficial in HOCM 2, 3
• Metabolic improvements: Enhanced insulin sensitivity and lipid profile improvements reduce overall cardiovascular risk 6
• Anti-inflammatory effects: Reduction in inflammatory markers like C-reactive protein may benefit cardiac remodeling 6

Important Caveats and Monitoring

Heart Failure Considerations

• HFpEF (preserved ejection fraction): GLP-1 receptor agonists are safe and may improve symptoms 4, 5
• HFrEF (reduced ejection fraction): Use with caution; potential risk of worsening HF events pending further data 4
• Recent decompensation: Avoid GLP-1 receptor agonists in patients with recent heart failure decompensation 3

Safety Monitoring

• Gastrointestinal effects: Nausea (17-44%), vomiting (7-25%), diarrhea (12-32%) are common but typically mild-to-moderate and transient 3
• Pancreatitis risk: Monitor for persistent severe abdominal pain; discontinue if pancreatitis suspected 2, 3
• Gallbladder disease: 38% increased risk of cholelithiasis/cholecystitis versus placebo 3
• Arrhythmia surveillance: Though the 2025 study showed no increased risk, continue routine monitoring given underlying HOCM 1

Contraindications Specific to This Patient

Absolute contraindications (must screen for):

• Personal or family history of medullary thyroid carcinoma 2, 3
• Multiple endocrine neoplasia type 2 (MEN2) 2, 3
• History of severe hypersensitivity to GLP-1 receptor agonists 3

Relative cautions (not contraindications):

• History of pancreatitis (use with caution; causality not definitively established) 2, 3
• Symptomatic gallstones (avoid if active gallbladder disease) 3
• Severe gastroparesis 3

Lifestyle Integration

GLP-1 receptor agonists must be combined with:

• Reduced-calorie diet (500-kcal daily deficit) 2, 3
• Minimum 150 minutes per week of moderate-intensity physical activity 2, 3
• Resistance training to preserve lean body mass 3
• Behavioral counseling and lifestyle modification support 2

Expected Outcomes and Follow-Up

Short-term (12-16 weeks):

• Evaluate treatment response: continue if ≥5% weight loss achieved 3
• Discontinue if <5% weight loss after 3 months at therapeutic dose 3
• Monitor for adverse effects and cardiac status 3

Long-term (beyond 6 months):

• Sustained weight loss of 14.9-20.9% depending on agent 2, 3
• Improved cardiovascular risk profile 1, 6
• Reduced heart failure hospitalization risk (based on HCM data) 1
• Lower all-cause mortality (based on HCM data) 1

Common Pitfalls to Avoid

1. Do not delay treatment due to HOCM diagnosis—the 2025 evidence supports use in this population 1
2. Do not assume HOCM is a contraindication—it is not listed in any guideline as a contraindication 2, 3
3. Do not skip slow titration—rapid dose escalation increases gastrointestinal side effects and discontinuation rates 3
4. Do not forget to adjust antihypertensive medications as weight loss progresses 2
5. Do not discontinue prematurely if early gastrointestinal symptoms occur—these typically resolve within 4-8 weeks 3
6. Do not combine with other GLP-1 receptor agonists—pharmacologically redundant and potentially harmful 3

Cost and Access Considerations

• Average wholesale price: $1,272-$1,619 per 30-day supply 3
• Insurance authorization may be challenging; document BMI and comorbidities 3
• Lifelong treatment typically necessary to maintain weight loss 3
• Payors should cover evidence-based obesity treatments to reduce barriers 3

The convergence of guideline recommendations for obesity treatment 2 with the groundbreaking 2025 real-world evidence specifically in HCM patients 1 provides strong support for using GLP-1 receptor agonists in this 56-year-old man with HOCM and obesity, with the expectation of both weight loss and improved cardiovascular outcomes.