What are the recommendations for using a new weight loss pill?

Weight Loss Medication Recommendations

For most patients with obesity (BMI ≥30 kg/m²) or overweight with comorbidities (BMI ≥27 kg/m²), semaglutide 2.4 mg weekly or tirzepatide should be the first-line pharmacotherapy choice due to superior efficacy (11-20% weight loss) and cardiovascular benefits. 1

Patient Selection Criteria

Pharmacotherapy is indicated for:

• BMI ≥30 kg/m² regardless of comorbidities 1
• BMI ≥27 kg/m² with at least one weight-related comorbidity (type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea) 1

Weight loss medications must be combined with lifestyle modifications including reduced-calorie diet and exercise—they are adjuncts, not standalone treatments. 2, 3

First-Line Medication Selection Algorithm

Tier 1: GLP-1/GIP Receptor Agonists (Preferred)

Tirzepatide produces the most potent weight loss:

• 15-20.9% mean weight reduction at 72 weeks in non-diabetic patients 4
• 12.4% greater weight loss compared to placebo 5
• Dose-dependent effects with 15 mg achieving maximum efficacy 4
• Administered subcutaneously once weekly 4
• Common adverse effects: nausea (31%), diarrhea (23%), vomiting (12%), constipation (5%) 4

Semaglutide 2.4 mg weekly is the alternative first-line option:

• 11.4% greater weight loss compared to placebo 5
• Similar gastrointestinal side effect profile to tirzepatide 5
• Slightly less potent than tirzepatide but still highly effective 4

Liraglutide 3.0 mg daily (Saxenda):

• 5.4% mean weight loss at 56 weeks 1
• 4.7% greater weight loss compared to placebo 5
• Requires daily subcutaneous injection with dose escalation from 0.6 mg, increasing by 0.6 mg weekly up to 3.0 mg 1
• Less potent than semaglutide or tirzepatide but still effective 1

Tier 2: Alternative First-Line Options

Phentermine/Topiramate ER (Qsymia):

• 6.6-8.0% mean weight loss at 1 year 1, 5
• Fixed-dose combination targeting multiple pathways 1
• Contraindications: cardiovascular disease, pregnancy, glaucoma, hyperthyroidism 1
• Requires monthly pregnancy testing for women of reproductive age 1
• Common adverse effects: paresthesia, constipation (20%) 5

Naltrexone/Bupropion:

• 4.1% greater weight loss compared to placebo 5
• Suitable for patients with depression or those attempting smoking cessation 6
• Constipation in approximately 20% of patients 5

Tier 3: Budget-Friendly Option

Orlistat (Xenical 120 mg/Alli 60 mg):

• 3.1% mean weight loss at 1 year 1, 5
• Blocks approximately 30% of dietary fat absorption 1
• Requires multivitamin supplementation (fat-soluble vitamins A, D, E, K) taken at bedtime 1, 3
• Take 1 capsule with each meal containing fat, maximum 3 capsules daily 3
• Common adverse effects: oily fecal spotting, urgency, gastrointestinal effects in >25% of patients 5
• Suitable for patients with cardiovascular contraindications to sympathomimetic agents 1

Tier 4: Short-Term Use Only

Phentermine monotherapy:

• 6.0 kg weight loss at 28 weeks, with 46% achieving ≥5% weight loss 1
• FDA-approved for short-term use only (a few weeks) 2
• Commonly prescribed off-label for longer duration 1
• Requires blood pressure and heart rate monitoring 1
• Contraindications: cardiovascular disease, uncontrolled hypertension, hyperthyroidism, within 14 days of MAO inhibitors 7

Special Populations

Patients with Type 2 Diabetes

Prioritize glucose-lowering medications with weight loss benefits: 2

• Tirzepatide or semaglutide are preferred due to dual benefits on glycemic control and weight 1
• Metformin, SGLT-2 inhibitors, GLP-1 agonists are weight-neutral or promote weight loss 2
• Avoid or minimize: insulin secretagogues, thiazolidinediones, insulin (associated with weight gain) 2

Patients with Constipation

Orlistat may be beneficial due to gastrointestinal effects promoting bowel movements. 1

Patients with Limited Financial Resources

Orlistat is the most affordable option, though less effective than newer agents. 1

Monitoring and Efficacy Assessment

Initial evaluation timeline:

• Assess monthly for the first 3 months, then quarterly 1
• Evaluate efficacy at 12-16 weeks on maximum tolerated dose 1, 4

Discontinuation criteria:

• <5% weight loss after 3 months at therapeutic dose warrants discontinuation or medication change 2, 1
• For liraglutide specifically: discontinue if <4% weight loss at 16 weeks 4

Long-term management:

• Continue medication beyond reaching weight loss goals to maintain benefits 1
• Obesity is a chronic disease requiring indefinite treatment 1
• Weight regain occurs rapidly upon discontinuation regardless of tapering strategy 4

Critical Pitfalls to Avoid

Do not combine phentermine with other weight loss medications or exceed recommended doses when tolerance develops. 1

Avoid β-blockers (atenolol, metoprolol, nadolol, propranolol) as antihypertensives in patients with obesity—they promote weight gain. 1, 7

Do not prescribe phentermine within 14 days of MAO inhibitors due to hypertensive crisis risk. 7

Women of reproductive age must use reliable contraception when taking teratogenic medications like phentermine/topiramate. 2, 1

Do not delay effective treatment by trialing unproven supplements when evidence-based medications are available. 7

Multivitamin supplementation is mandatory with orlistat to prevent fat-soluble vitamin deficiency. 1, 3

Medications to Avoid in Obesity Management

Never use nutritional supplements, herbs, or botanicals for obesity management—there is no clear evidence of efficacy, with most trials being low quality and high risk for bias. 7

Minimize or switch medications that promote weight gain: 7

• Certain antipsychotics
• Tricyclic antidepressants
• Insulin secretagogues
• β-blockers