What are the appropriate pharmacologic weight‑loss options for a 67‑year‑old woman with BMI 33, well‑controlled hypothyroidism, hyperlipidemia, stage 3 chronic kidney disease (impaired renal function), depression, and fibromyalgia?

Weight-Loss Pharmacotherapy for a 67-Year-Old Woman with BMI 33, Stage 3 CKD, and Multiple Comorbidities

GLP-1 receptor agonist therapy—specifically liraglutide 3.0 mg daily—is the appropriate first-line pharmacologic option for this patient, as it is the only FDA-approved anti-obesity medication with demonstrated safety in moderate renal impairment (eGFR 30–59 mL/min/1.73 m²) and does not require dose adjustment in stage 3 CKD. 1, 2, 3

Eligibility and Indication

• This patient meets criteria for pharmacologic weight management with BMI ≥ 30 kg/m² and multiple obesity-related comorbidities (hyperlipidemia, chronic kidney disease). 1, 2
• Her well-controlled hypothyroidism (TSH 1.75, free T4 1.17) does not contraindicate weight-loss medication and should not delay initiation of therapy. 4, 5
• Pharmacotherapy must be combined with a 500–1,000 kcal daily deficit, ≥150 minutes/week of moderate-intensity aerobic activity, and behavioral counseling; medication alone is insufficient. 1, 2

First-Line Recommendation: Liraglutide 3.0 mg Daily

Liraglutide is the preferred GLP-1 receptor agonist in this clinical scenario because:

• Proven safety in moderate renal impairment: A 26-week randomized controlled trial specifically enrolled patients with eGFR 30–59 mL/min/1.73 m² (matching this patient's eGFR of 50) and demonstrated efficacy without dose adjustment. 3
• Expected weight loss: 5.2–6.1% of baseline body weight over 6–12 months. 2
• Daily subcutaneous injection may offer better adherence monitoring in elderly patients compared to weekly formulations. 2

Dosing and Titration

• Start at 0.6 mg daily for week 1, then increase by 0.6 mg weekly increments to the maintenance dose of 3.0 mg daily by week 5. 2
• Slow titration reduces gastrointestinal adverse events (nausea 17–44%, diarrhea 12–32%), which are typically mild-to-moderate and diminish over time. 2

Contraindications to Verify

• Absolute contraindications: personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN 2); pregnancy or intention to conceive. 2
• This patient's depression and fibromyalgia are not contraindications to GLP-1 therapy. 2

Alternative Agents (Second-Line if Liraglutide Is Not Tolerated)

If liraglutide causes intolerable gastrointestinal side effects or is otherwise unsuitable:

Orlistat 120 mg Three Times Daily

• The only weight-loss medication with proven cardiovascular safety in high-risk populations, making it appropriate for elderly patients with multiple comorbidities. 2
• Expected weight loss: modest 3.1% at 1 year. 2
• Mechanism: inhibits pancreatic lipase, reducing dietary fat absorption by ~30%. 2
• Adverse events: oily stools, fecal urgency, flatulence; requires supplementation with fat-soluble vitamins (A, D, E, K). 2
• No renal dose adjustment required and safe in stage 3 CKD. 2

Agents to Avoid in This Patient

• Phentermine and phentermine/topiramate are contraindicated if the patient has any cardiovascular disease (not explicitly stated but common in elderly patients with CKD and hyperlipidemia); these sympathomimetic agents carry cardiovascular risk. 2
• Naltrexone SR + bupropion SR should be used cautiously given her depression history, as it carries neuro-psychiatric risks including worsening depression and suicidal ideation. 2
• Semaglutide 2.4 mg weekly and tirzepatide 15 mg weekly lack specific safety data in moderate renal impairment and are not FDA-approved for use in stage 3 CKD without caution. 2, 3

Monitoring and Continuation Criteria

• Monthly visits for the first 3 months to assess weight loss, blood pressure, gastrointestinal tolerability, and adherence. 1, 2
• Discontinue therapy if <5% weight loss after 12 weeks at the maintenance dose, as early response predicts long-term success. 1, 2
• Every 3 months thereafter: monitor weight, blood pressure, lipid profile, renal function (eGFR, creatinine), and thyroid function (TSH annually). 1, 2, 6

Special Considerations in Stage 3 CKD

• Thyroid dysfunction is common in CKD (38.6% prevalence, predominantly subclinical hypothyroidism), but this patient's thyroid is well-controlled and does not require adjustment before starting weight-loss medication. 6
• Dyslipidemia is present in 34–36% of stage 3 CKD patients; weight loss via GLP-1 therapy may improve lipid parameters (triglycerides, LDL cholesterol). 6
• Progression of CKD increases cardiovascular risk; weight loss of 5–10% can reduce cardiovascular risk factors and slow CKD progression. 1, 6

Critical Pitfalls to Avoid

• Do not delay pharmacotherapy while waiting for "optimal" lifestyle modification; concurrent initiation improves outcomes. 1, 2
• Do not prescribe sympathomimetic agents (phentermine, phentermine/topiramate) without confirming absence of cardiovascular disease, which is highly prevalent in elderly patients with CKD and hyperlipidemia. 2
• Do not continue medication beyond 12 weeks if <5% weight loss is achieved; switch to an alternative agent or consider metabolic surgery (BMI ≥35 kg/m² with comorbidities). 1, 2
• Do not assume hypothyroidism is undertreated based on weight concerns alone; her TSH of 1.75 is well within the age-appropriate target (upper limit ~7.5 mIU/L for patients >65 years). 5
• Do not overlook peri-operative risk: if elective surgery is planned, discontinue liraglutide at least 3 weeks beforehand due to delayed gastric emptying and aspiration risk. 2

Long-Term Management

• Continuous therapy is required to sustain weight loss; abrupt cessation typically results in regain of 50–67% of lost weight within 12 months. 2
• If weight loss plateaus or inadequate response occurs despite adherence, consider metabolic surgery for BMI ≥35 kg/m² with comorbidities (CKD, hyperlipidemia). 1
• Lifelong lifestyle support (dietary counseling, physical activity, behavioral therapy) must continue alongside pharmacotherapy. 1, 2