How to prescribe Semaglutide (glucagon-like peptide-1 receptor agonist) for weight loss in a hypothyroid woman?

Prescribing Semaglutide for Weight Loss in a 60-Year-Old Woman with Hypothyroidism

Start semaglutide at 0.25 mg subcutaneously once weekly and titrate upward every 4 weeks to reach the maintenance dose of 2.4 mg weekly after 16 weeks, while closely monitoring thyroid function and anticipating the need to reduce levothyroxine dosage as weight loss occurs. 1, 2, 3

Pre-Treatment Screening and Contraindications

Before initiating semaglutide, 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 1, 4
• Pregnancy or breastfeeding - absolute contraindication 2, 4
• History of pancreatitis or gallbladder disease - use with caution but not an absolute contraindication 2, 4

Hashimoto's thyroiditis is NOT a contraindication to semaglutide use. 4 The medication is safe in patients with autoimmune hypothyroidism, though thyroid function monitoring becomes critical during treatment.

Dosing Protocol and Titration Schedule

Follow this exact titration schedule to minimize gastrointestinal side effects: 1, 2, 3

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

Administer at any time of day, with or without meals, injecting subcutaneously in the abdomen, thigh, or upper arm. 3 If a dose is missed, administer within 5 days of the missed dose. 3

Critical Thyroid Management Considerations

This is the most important aspect for your hypothyroid patient: As semaglutide induces weight loss, levothyroxine requirements will decrease, potentially causing iatrogenic hyperthyroidism if the dose is not adjusted. 5

Monitoring schedule for thyroid function:

• Baseline: Check TSH and free T4 before starting semaglutide
• Every 4-6 weeks during active weight loss: Monitor TSH, free T4, and clinical symptoms of hyperthyroidism (palpitations, tremor, anxiety, heat intolerance) 5
• Anticipate levothyroxine dose reduction: As a general rule, levothyroxine dosing is approximately 1.6 mcg/kg body weight - expect to reduce the dose proportionally as weight decreases 5

The mechanism is either increased absorption of levothyroxine with weight loss or the weight loss itself creating a supratherapeutic levothyroxine level. 5 Do not wait for symptoms - proactively reduce levothyroxine as significant weight loss occurs.

Expected Weight Loss Outcomes

Semaglutide 2.4 mg weekly produces mean weight loss of 14.9% at 68 weeks in patients without diabetes. 6, 1 In the STEP 1 trial, this compared to 2.4% weight loss with placebo (difference of 12.4%). 6 Your patient should achieve at least 5% weight loss by 16 weeks on the maintenance dose to be considered a responder. 2

Weight loss is typically greater in non-diabetic patients (6.1-17.4%) compared to those with diabetes (4-6.2%). 1

Lifestyle Modifications (Non-Negotiable)

Semaglutide must be combined with lifestyle changes - it is not effective as monotherapy. 1 Counsel your patient on:

• Reduced-calorie diet: Encourage a 500-750 calorie daily deficit 6, 2
• Physical activity: Target 150-200 minutes per week of moderate-intensity exercise 6
• Resistance training: Essential to preserve lean body mass during weight loss 1

Common Side Effects and Management

Gastrointestinal effects are the most common adverse events: 1, 4

• Nausea (17-44% of patients)
• Diarrhea (16-32%)
• Constipation (10-23%)
• Vomiting (7-25%)

These are typically mild-to-moderate, transient, and decrease over time. 1 The gradual titration schedule minimizes these effects. 2, 4 Weight loss with semaglutide is NOT primarily mediated by nausea/vomiting - studies show nausea contributes less than 0.1 kg to total weight loss. 7

Strategies to minimize GI symptoms:

• Reduce meal size
• Limit alcohol and carbonated drinks
• Eat slowly 1

Serious Adverse Events Requiring Monitoring

Monitor for these potentially serious complications: 1, 4

• Pancreatitis: Watch for persistent severe abdominal pain - occurs in clinical trials but causality not definitively established 1, 4
• Gallbladder disease: Risk of cholelithiasis and cholecystitis is increased 1, 4
• Delayed gastric emptying: Increases aspiration risk during anesthesia - if surgery is planned, consider discontinuing 10-14 days beforehand 2

Semaglutide carries a 38% higher risk of serious adverse events compared to placebo overall. 4

Cardiovascular Benefits (Relevant for This Age Group)

Semaglutide provides significant cardiovascular protection beyond weight loss. 1 In the SELECT trial, semaglutide 2.4 mg reduced the composite incidence of cardiovascular death, nonfatal MI, or nonfatal stroke by 20% (HR 0.80) in patients with cardiovascular disease and BMI ≥27. 1 In SUSTAIN-6, the hazard ratio was 0.74 (95% CI 0.58-0.95). 1

Long-Term Use and Weight Maintenance

Counsel your patient that semaglutide requires lifelong use for sustained weight loss. 1 After cessation, significant weight regain occurs:

• 11.6% of lost weight regained after 52 weeks of follow-up 6, 1
• In STEP 4, participants who switched to placebo regained 6.9% of lost weight over 48 weeks 6

Drug Interactions and Concomitant Medications

• Review all current medications and minimize those promoting weight gain (e.g., mirtazapine, amitriptyline, gabapentin) 6, 2
• If taking insulin or sulfonylureas: Reduce doses to prevent hypoglycemia 6, 4
• Oral contraceptives: Delayed gastric emptying may affect absorption - consider non-oral contraception or barrier methods 4
• Do not combine with other GLP-1 receptor agonists or DPP-4 inhibitors 1

Follow-Up Schedule

Assess your patient at least every 3 months for: 1

• Weight loss progress
• Cardiovascular risk factors
• Medication adherence
• Thyroid function (TSH, free T4)
• Blood pressure (may need to reduce antihypertensives as weight decreases) 1
• Signs of pancreatitis or gallbladder disease

Evaluate efficacy at 12-16 weeks on maximum tolerated dose. 1 If inadequate response (<5% weight loss), consider intensifying treatment with additional approaches. 1

Cost and Insurance Considerations

The average wholesale price is approximately $1,600 for a 30-day supply. 1 Insurance authorization may be challenging, particularly for obesity management without diabetes. 1 Document failed lifestyle modifications (diet and exercise) for both clinical appropriateness and insurance authorization. 2