What is the best approach for a patient with a body mass index (BMI) of 31, hypertension (HTN), and a family history of myocardial infarction (MI), who is requesting Glucagon-like peptide-1 (GLP-1) receptor agonists, such as liraglutide (Victoza) or semaglutide (Ozempic), for weight loss?

GLP-1 Receptor Agonist Therapy for Weight Loss in a Patient with BMI 31, Hypertension, and Family History of MI

You should prescribe semaglutide 2.4mg weekly (Wegovy) for this patient, as they meet FDA criteria (BMI ≥27 with weight-related comorbidity) and the medication provides both substantial weight loss and proven cardiovascular risk reduction. 1, 2

Patient Eligibility and Rationale

Your patient with BMI 31 and hypertension qualifies for GLP-1 receptor agonist therapy under two criteria: BMI ≥30 kg/m² (obesity) without additional requirements, and BMI ≥27 kg/m² with at least one weight-related comorbidity such as hypertension 1, 2. The family history of MI, while not a direct indication, makes cardiovascular protection particularly valuable for this patient 1.

Semaglutide 2.4mg weekly achieves 14.9% total body weight loss at 68 weeks, with 64.9% of patients achieving ≥10% weight loss 1. More importantly for this patient's cardiovascular concerns, semaglutide reduces the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 20% (HR 0.80) in patients with cardiovascular disease and BMI ≥27, even without diabetes 1.

Pre-Treatment Screening Requirements

Before prescribing, you must screen for absolute contraindications:

• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 (MEN2) - this is an absolute contraindication based on animal studies showing thyroid C-cell tumors 3, 1, 2, 4, 5
• History of severe hypersensitivity reaction to semaglutide 3, 4
• Current pregnancy or breastfeeding 2, 5

Obtain baseline laboratory testing including comprehensive metabolic panel, lipid panel (total cholesterol, LDL, HDL, triglycerides), and HbA1c to assess baseline cardiovascular risk 1. Document history of pancreatitis, as this requires caution though causality has not been definitively established 3, 1.

Dosing and Titration Protocol

Start semaglutide at 0.25mg subcutaneously once weekly and follow this mandatory titration schedule to minimize gastrointestinal side effects 1, 2:

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

The medication can be injected in the abdomen, thigh, or upper arm, rotating injection sites to reduce risk of cutaneous amyloidosis 4. It may be taken with or without food 4, 5.

Concomitant Medication Management

Since your patient has hypertension, monitor blood pressure closely as weight loss progresses, as antihypertensive medication requirements may decrease 1. You may need to reduce or discontinue some antihypertensive agents to prevent hypotension as the patient loses weight 1.

If the patient were on sulfonylureas or insulin (not mentioned but important to note), you would need to reduce these by 20-50% to prevent hypoglycemia 1, 4.

Essential Lifestyle Modifications

GLP-1 receptor agonists must be combined with lifestyle interventions - this is not optional 1, 2, 6:

• Caloric deficit: 500-kcal reduction below daily requirements 1
• Physical activity: Minimum 150 minutes per week of moderate activity 1, 2
• Resistance training: Essential to preserve lean body mass and prevent muscle loss during weight loss 1, 2, 6

Without these lifestyle modifications, weight loss will be suboptimal 6.

Monitoring Schedule

During titration phase (first 16 weeks): Assess every 4 weeks for gastrointestinal tolerance, weight loss progress, blood pressure, and signs of pancreatitis or gallbladder disease 1.

After reaching maintenance dose: Monitor at least every 3 months for weight stability, blood pressure, cardiovascular risk factors, and medication adherence 1.

Critical decision point at 12-16 weeks: If weight loss is <5% after 3 months at therapeutic dose, discontinue the medication and consider alternative approaches 1, 2.

Expected Outcomes and Cardiovascular Benefits

Beyond weight loss, your patient should experience:

• Blood pressure reduction through multiple mechanisms 1
• Improved lipid profiles with triglyceride reduction and HDL increase 7
• Reduced inflammatory markers like C-reactive protein 1
• 20% reduction in cardiovascular events if they have or develop cardiovascular disease 1

Managing Common Side Effects

Gastrointestinal effects (nausea, vomiting, diarrhea) occur in the majority of patients but are typically mild-to-moderate and transient 1, 4, 6. Mitigation strategies include:

• Slow titration (already built into the protocol) 1
• Reducing meal size 1
• Limiting alcohol and carbonated beverages 1
• Eating smaller, more frequent meals 6

Serious but rare risks requiring immediate discontinuation include:

• Pancreatitis: Persistent severe abdominal pain radiating to the back 1, 4, 5
• Gallbladder disease: Cholelithiasis or cholecystitis symptoms 1, 4
• Severe allergic reactions: Swelling of face/lips/tongue, difficulty breathing 4, 5

Long-Term Treatment Expectations

This patient must understand that lifelong treatment is typically necessary 1, 2, 8. Sudden discontinuation results in regain of 50-67% of lost weight within 1 year 1, 2, 8. Weight regain of 11.6% of lost weight occurred after 52 weeks post-discontinuation in clinical trials 1.

The medication costs approximately $1,557-$1,619 per 30-day supply, requiring long-term financial planning 1. Insurance authorization may be challenging, particularly for obesity management without diabetes 1.

Alternative Consideration: Tirzepatide

While semaglutide is the appropriate choice for this patient, tirzepatide 15mg weekly achieves superior weight loss (20.9% at 72 weeks) compared to semaglutide (14.9%) 1. However, semaglutide remains preferred for this patient because:

1. Proven cardiovascular benefit in patients with obesity and cardiovascular risk factors 1
2. Lower cost ($1,272 vs $1,557-$1,619 per month) 1
3. More established safety profile 1

If this patient fails to achieve adequate weight loss on semaglutide 2.4mg after 3-6 months, switching to tirzepatide would be reasonable 1.

Critical Pitfalls to Avoid

• Do not prescribe lower-dose semaglutide (Ozempic 1mg) for weight loss - the 2.4mg dose (Wegovy) is required for obesity management and cardiovascular benefit 1
• Do not skip the titration schedule - starting at higher doses dramatically increases gastrointestinal side effects and treatment discontinuation 1, 2
• Do not fail to counsel on lifelong treatment - patients who discontinue will regain most of their lost weight 1, 2, 8
• Do not ignore perioperative considerations - if elective surgery is planned, discontinue semaglutide at least 3 weeks before due to delayed gastric emptying and aspiration risk 1

Contraception Counseling (if applicable)

If your patient is a woman of childbearing potential, provide contraception counseling as GLP-1 medications can alter metabolism of oral contraceptives due to delayed gastric emptying 2. Consider switching to non-oral contraceptive methods or adding barrier contraception 1.