Combination Weight Loss Medications

Introduction to Combination Therapies

The American College of Gastroenterology recommends the use of FDA-approved combination weight loss drugs, such as phentermine/topiramate extended-release (Qsymia) and naltrexone/bupropion sustained-release (Contrave), for chronic weight management in adults with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities, used as adjuncts to reduced-calorie diet and increased physical activity 1, 2

The American Gastroenterological Association suggests that phentermine is a sympathomimetic amine that elevates norepinephrine in the CNS to suppress appetite, while topiramate modulates gamma-aminobutyric acid receptors, inhibits carbonic anhydrase, and antagonizes glutamate to reduce food intake and increase satiation 1, 2
This combination produces 7.8% weight loss at the 7.5/46 mg dose and 9.8% at the 15/92 mg dose compared to 1.2% with placebo, with 62% and 70% of patients achieving ≥5% weight loss at these respective doses 3
The American College of Cardiology recommends starting with 3.75/23 mg daily for 14 days, then increasing to 7.5/46 mg daily as the standard maintenance dose 1, 3, 4
Discontinue if <3% weight loss after 12 weeks at 7.5/46 mg, or <5% weight loss after 12 weeks at 15/92 mg 1, 3, 4

The American Gastroenterological Association suggests that bupropion (dopamine/norepinephrine reuptake inhibitor) and naltrexone (opioid receptor antagonist) work synergistically to activate POMC neurons in the arcuate nucleus, causing release of alpha-melanocyte-stimulating hormone, a potent anorectic neuropeptide 1
Start with 1 tablet daily, increase by 1 tablet weekly to maximum dose of 2 tablets in the morning and 2 tablets in the evening (32/360 mg total daily) 1
Discontinue if <5% weight loss at 12 weeks 1

The American Diabetes Association recommends liraglutide (Saxenda) at 3.0 mg daily for chronic weight management, producing 5.4% placebo-subtracted weight reduction at 12 months 1
Start at 0.6 mg daily, increase by 0.6 mg weekly until 3.0 mg is reached 1
Discontinue if <4% weight loss at 16 weeks 1

The American Heart Association suggests that for patients with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities requiring pharmacotherapy, the first-line choice is phentermine/topiramate ER for greatest weight loss efficacy (6.8% placebo-subtracted reduction), particularly in younger patients requiring appetite suppression 2, 3