What are the alternatives for rapid weight loss in a patient with paresthesia who cannot take Zepbound (tirzepatide)?

Alternative Weight Loss Options After Discontinuing Zepbound Due to Paresthesia

Since paresthesia is a known side effect of phentermine/topiramate (Qsymia), you should avoid this medication and instead consider other FDA-approved anti-obesity medications that do not cause paresthesias, with semaglutide (Wegovy/Saxenda) being the preferred alternative given its superior efficacy and cardiovascular benefits. 1

Why Paresthesia Matters in Medication Selection

• Phentermine/topiramate ER (Qsymia) is contraindicated in your patient's case because paresthesias are the most common side effect, occurring due to the topiramate component 1
• The fact that your patient developed paresthesia on tirzepatide (Zepbound) suggests heightened sensitivity to neurological side effects, making Qsymia a poor choice despite its 6.6% mean weight loss efficacy 1

Recommended Alternative Medications (In Order of Preference)

First-Line: GLP-1 Receptor Agonists

Semaglutide (Wegovy) is your best alternative, offering:

• 15.8% mean weight loss at 68 weeks (significantly higher than other options) 1
• Proven cardiovascular benefit: 20% reduction in cardiovascular death, MI, or stroke in the SELECT trial for patients with pre-existing CVD who are overweight/obese 1
• No paresthesia as a side effect - main adverse effects are gastrointestinal (nausea, diarrhea, constipation) 1
• Dosing: Start 0.25 mg weekly subcutaneously, escalate by 0.25 mg every 4 weeks up to 2.4 mg weekly 1

Liraglutide 3.0 mg (Saxenda) as a second GLP-1 option:

• 5.4% mean weight loss at 56 weeks 1
• Similar side effect profile to semaglutide but less effective 1
• Dosing: Start 0.6 mg daily, escalate by 0.6 mg weekly up to 3.0 mg daily subcutaneously 1

Second-Line Options (If GLP-1s Are Not Tolerated or Available)

Naltrexone SR/Bupropion SR (Contrave):

• 4.8% mean weight loss at 56 weeks 1
• No paresthesia risk - side effects include nausea, constipation, dizziness, insomnia 1
• Good option if patient has depression or is on SSRIs, as bupropion may provide mood benefits 1
• Dosing: Start 8/90 mg daily, escalate to 16/180 mg twice daily 1

Orlistat (Xenical):

• 3.1% mean weight loss at 1 year (least effective but safest) 1
• Completely different mechanism (lipase inhibitor) with no neurological side effects 1
• Side effects are entirely gastrointestinal (oily stools, fecal urgency) 1
• Best for patients with cardiovascular disease who cannot take sympathomimetics 1
• Dosing: 120 mg three times daily with meals 1

Avoid These Medications

Do NOT use:

• Phentermine/topiramate ER (Qsymia) - paresthesias are the primary side effect 1
• Phentermine alone - if patient has cardiovascular disease, as it is a sympathomimetic agent 1, 2

Critical Implementation Points

Medication Must Be Combined With Lifestyle Intervention

• Pharmacotherapy should never be used alone but always combined with intensive lifestyle programs including diet, exercise, and behavioral modification 1
• Weight loss medications work by decreasing appetite, increasing satiation, enhancing satiety, and increasing resting energy expenditure 1

Efficacy Assessment Timeline

• Evaluate at 12 weeks: If <5% weight loss achieved, discontinue and switch to alternative medication 1
• Monthly monitoring for first 3 months, then every 3 months thereafter 1

Long-Term Continuation

• Weight management pharmacotherapy should be continued beyond reaching weight loss goals to maintain health benefits, as discontinuation often results in weight regain 3
• Obesity requires a "continuous treatment model" across the lifespan 4

Common Pitfalls to Avoid

1. Don't prescribe sympathomimetics (phentermine, Qsymia) if patient has cardiovascular disease - use orlistat or GLP-1 agonists instead 1

2. Don't forget contraception counseling - if prescribing to individuals of childbearing potential, especially with medications that have teratogenic risks 3

3. Don't ignore vitamin supplementation - if using orlistat, patient needs multivitamin (taken separately) due to fat-soluble vitamin malabsorption 1

4. Don't expect uniform results - there is enormous variability in weight loss response to all treatments, and no prospective studies show that personalized approaches based on genotype/phenotype yield uniform success 4