What are the recommended medications and dosages for weight loss?

Recommended Medications for Weight Loss

For patients with obesity (BMI ≥30) or overweight (BMI ≥27) with weight-related comorbidities, tirzepatide offers the greatest weight loss effect (21% at 72 weeks) and should be the first-line pharmacological option when available, used in conjunction with comprehensive lifestyle modifications. 1

Patient Selection for Pharmacotherapy

• Pharmacotherapy should be offered to patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities (hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea) who have failed to achieve weight loss goals through diet and exercise alone 1
• Medication should not be used alone but combined with an intensive lifestyle program including diet, exercise, and behavioral modification 1
• A doctor-patient discussion about medication side effects, lack of long-term safety data, and the temporary nature of medication-induced weight loss should occur before initiating therapy 1

First-Line Medications and Dosages

GLP-1 Receptor Agonists and Related Medications

• Tirzepatide (glucose-dependent insulinotropic polypeptide/GLP-1 agonist): Greatest effect with mean weight loss of 21% at 72 weeks 1
• Semaglutide: Significant weight loss, part of the GLP-1 agonist class 1
• Liraglutide 3.0 mg (Saxenda): Average 5.4% weight loss at 56 weeks compared to placebo 1

Other FDA-Approved Options for Long-Term Use

• Phentermine-topiramate ER (Qsymia): Average 6.6% weight loss at 1 year compared to placebo 1
• Naltrexone-bupropion SR (Contrave): Average 4.8% weight loss at 56 weeks compared to placebo 1
• Orlistat (Xenical): Average 3.1% weight loss at 1 year compared to placebo 1

Short-Term Use Only

• Phentermine (Adipex, Lomaira): Short-term (few weeks) adjunct to lifestyle modifications 1
• Diethylpropion: Short-term use only, with caution due to potential cardiovascular risks 2

Medication Selection Algorithm

1. First assess for contraindications:

   • For patients with cardiovascular disease: Avoid sympathomimetic agents like phentermine and phentermine/topiramate ER 1
   • For women of reproductive age: Ensure reliable contraception 1

2. For patients with type 2 diabetes:

   • Prioritize medications that promote both weight loss and glycemic control:
     • GLP-1 agonists (semaglutide, liraglutide)
     • Tirzepatide
     • Metformin 1

3. For patients without diabetes:

   • Consider side effect profiles and patient preferences:
     • For those concerned about gastrointestinal side effects: Consider naltrexone-bupropion
     • For those with medication adherence challenges: Consider once-weekly options like semaglutide
     • For those with cardiovascular concerns: Avoid sympathomimetics 1

Monitoring and Follow-Up

• Assess efficacy and safety at least monthly for the first 3 months, then at least every 3 months 1
• If weight loss is <5% after 12 weeks (or 3 months for some medications), discontinue the medication and consider alternatives 1
• For long-term maintenance, continued patient-practitioner contact is essential 3

Important Considerations and Caveats

• Weight loss medications produce modest results (<5 kg at 1 year) when used alone, but can significantly improve weight-related comorbidities when combined with lifestyle changes 1
• The optimal duration of treatment has not been determined, with most randomized controlled trials examining only up to 12 months of therapy 1
• High levels of physical activity (225-420 min/week of moderate intensity) are associated with improved weight maintenance compared to lower levels 4
• Comprehensive lifestyle modification should always accompany pharmacotherapy, including dietary changes, increased physical activity, and behavioral therapy 5, 6
• Weight regain is common after medication discontinuation, emphasizing the need for sustained lifestyle modifications 3

Comprehensive Approach

• A comprehensive weight loss program should include:
  • Reduced-calorie diet (portion-controlled diets, including meal replacements, may be more effective) 3
  • Increased physical activity (at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic exercise weekly) 4
  • Behavioral therapy focusing on self-monitoring, dietary counseling, and problem-solving 5
  • Pharmacotherapy as an adjunct when appropriate 1