What are the medications used for weight loss?

Weight Loss Medications

GLP-1 receptor agonist-based medications—specifically semaglutide 2.4 mg weekly or tirzepatide—are the first-line pharmacotherapy for weight loss due to superior efficacy and proven cardiovascular benefits. 1, 2

Indications for Pharmacotherapy

Prescribe weight loss medications for patients meeting these criteria: 1, 2, 3

• BMI ≥30 kg/m² (obesity), OR
• BMI ≥27 kg/m² with weight-related comorbidities including:
  • Type 2 diabetes
  • Hypertension
  • Dyslipidemia
  • Obstructive sleep apnea

All medications must be combined with intensive lifestyle intervention—never use pharmacotherapy alone. 1

First-Line Medications (Ranked by Efficacy)

GLP-1 Receptor Agonist-Based Agents

Semaglutide 2.4 mg (Wegovy) 1

• Mean weight loss: 15% at 1 year (most effective available)
• Dosing: Once-weekly subcutaneous injection
• Key benefits: Reduces lipids, blood pressure, glucose; proven cardiovascular benefits in patients with obesity
• Side effects: Gastrointestinal (nausea, vomiting, diarrhea)—transient during dose escalation, minimized with slow titration
• Approved for long-term use

Tirzepatide (Zepbound) 1, 2

• Dual GIP/GLP-1 receptor agonist
• Efficacy: Comparable or superior to semaglutide 2.4 mg
• Same cardiovascular and metabolic benefits as GLP-1 agonists
• Approved for long-term use

Liraglutide 3.0 mg (Saxenda) 1, 2, 3

• Mean weight loss: 5.4% at 56 weeks
• Dosing: Daily subcutaneous injection; start 0.6 mg daily, escalate by 0.6 mg weekly to 3.0 mg
• Side effects: Nausea, hypoglycemia, diarrhea, constipation, vomiting, headache
• Approved for long-term use

Combination Agents

Phentermine/Topiramate ER (Qsymia) 1, 2, 3

• Mean weight loss: 6.6-9.8% at 1 year
• Mechanism: Sympathomimetic (appetite suppression) + GABA modulation (neurostabilizer)
• Dosing: Start 3.75/23 mg daily, escalate gradually to maximum 15/92 mg daily
• Side effects: Paresthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth, increased heart rate
• Contraindications: Cardiovascular disease, pregnancy, glaucoma, hyperthyroidism, untreated closed-angle glaucoma
• Schedule IV controlled substance
• Approved for long-term use

Naltrexone SR/Bupropion SR (Contrave) 1, 4, 5

• Mean weight loss: 4.0-4.8% at 56 weeks
• Mechanism: Opioid receptor antagonist + dopamine/norepinephrine reuptake inhibitor
• Dosing: Start 8/90 mg daily (AM), escalate to 16/180 mg BID
• Side effects: Nausea, constipation, dizziness, insomnia, dry mouth, increased risk of seizure, suicidal thoughts/behaviors
• Approved for long-term use

Lipase Inhibitor

Orlistat (Xenical 120 mg/Alli 60 mg OTC) 1, 2, 3

• Mean weight loss: 2.9-3.1% at 1 year (least effective)
• Mechanism: Blocks ~30% of dietary fat absorption via pancreatic/gastric lipase inhibition
• Dosing: 120 mg three times daily with meals
• Side effects: Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, increased defecation, fecal incontinence
• Requires fat-soluble vitamin supplementation (A, D, E, K)
• Budget-friendly option; safe in cardiovascular disease
• Approved for long-term use

Short-Term Medications (≤12 weeks)

Phentermine (Adipex) 1, 3, 6

• Mean weight loss: 3.6-6.0 kg at 28 weeks; 46% achieve ≥5% weight loss
• Dosing: 15-30 mg daily, approximately 2 hours after breakfast
• Mechanism: Sympathomimetic amine (appetite suppression)
• Side effects: Dizziness, dry mouth, difficulty sleeping, irritability, increased heart rate and blood pressure
• Contraindications: Cardiovascular disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension, hyperthyroidism, glaucoma, pregnancy, nursing, history of drug abuse, within 14 days of MAOIs
• Schedule IV controlled substance
• FDA-approved for short-term use only (<12 weeks), though commonly prescribed off-label long-term

Diethylpropion 1, 7

• Mean weight loss: 3.0 kg (borderline statistical significance)
• Mechanism: Sympathomimetic amine similar to amphetamines
• Duration: 6-52 weeks in studies
• Short-term use only

Clinical Decision Algorithm

Step 1: Assess Contraindications 1, 2, 3

Cardiovascular disease present?

• Avoid: Phentermine, phentermine/topiramate ER
• Safe alternatives: GLP-1 agonists (preferred), orlistat, naltrexone/bupropion

Type 2 diabetes present?

• Preferred: GLP-1 agonists (semaglutide 2.4 mg, tirzepatide, liraglutide 3.0 mg)—reduce hyperglycemia in addition to weight loss
• Add metformin as first-line antidiabetic agent

Pregnancy or women of reproductive age without reliable contraception?

• Contraindicated: All weight loss medications
• Require monthly pregnancy testing if prescribing phentermine/topiramate ER

Glaucoma present?

• Contraindicated: Phentermine, phentermine/topiramate ER

History of seizures or eating disorders?

• Contraindicated: Naltrexone/bupropion

Severe renal impairment (eGFR 15-29 mL/min/1.73 m²)?

• Phentermine maximum dose: 15 mg daily
• Avoid if eGFR <15 mL/min/1.73 m² or dialysis-dependent

Step 2: Select First-Line Agent 1, 2, 3

For most patients: Semaglutide 2.4 mg weekly OR tirzepatide (superior efficacy, cardiovascular benefits)

If GLP-1 agonists contraindicated/unavailable: Phentermine/topiramate ER (if no cardiovascular disease)

If cardiovascular disease present: Liraglutide 3.0 mg OR orlistat

If constipation present or limited financial resources: Orlistat

If expedited weight loss needed and no cardiovascular contraindications: Phentermine monotherapy (short-term)

Step 3: Monitoring and Efficacy Assessment 1, 2, 3

Initial monitoring: 2, 3

• Monthly for first 3 months
• Then quarterly thereafter

Efficacy threshold: 1, 2, 3

• Discontinue or switch medication if <5% weight loss after 3 months at therapeutic dose
• This is a critical decision point—do not continue ineffective therapy

Specific monitoring by medication: 2, 3

• Phentermine/phentermine-topiramate: Blood pressure, heart rate, signs of pulmonary hypertension (dyspnea, angina, syncope, edema)
• Orlistat: Fat-soluble vitamin levels (A, D, E, K); ensure multivitamin compliance
• Phentermine/topiramate ER: Monthly pregnancy testing for women of reproductive age

Long-term management: 3

• Continue medication beyond reaching weight loss goals to maintain benefits—obesity is a chronic disease requiring indefinite treatment
• Do not exceed recommended doses when tolerance develops; discontinue and switch agents instead

Critical Pitfalls and Contraindications

Never combine phentermine with other weight loss medications or serotonergic agents (SSRIs)—safety and efficacy not established. 1, 6

Never use β-blockers as antihypertensives in patients with obesity—they promote weight gain. 3

Never exceed recommended phentermine doses when tolerance develops—discontinue instead. 3, 6

Avoid concomitant alcohol use with phentermine—may result in adverse drug reactions. 6

Do not prescribe weight loss medications as monotherapy—always combine with intensive lifestyle intervention. 1