| Drug | Comments | Dose | Efficacy for weight loss* | Side effects |
| High efficacy |
| GLP-1 receptor agonists: | - Semaglutide and liraglutide are approved for weight loss for 12 years and older (United States)
- Decrease hunger by acting directly on the central nervous system to decrease appetite and increase satiety and by slowing gastric emptying
- Other GLP-1 receptor agonists are approved for treatment of T2DM but not for obesity
| - Semaglutide – Starting dose 0.25 mg subcutaneously once weekly; titrate gradually as tolerated to target dose of 2.4 mg once weekly
- Liraglutide – Starting dose is 0.6 mg subcutaneously once daily; titrate gradually as tolerated to target dose of 3 mg once daily
| - Semaglutide – Mean weight loss 17.7 kg; BMI loss 6.0 kg/m2 (16.7%)[2]
- Liraglutide – Mean weight loss 4.5 kg; BMI loss 1.6 kg/m2 (4.6%)[3]
| - Nausea
- Vomiting
- Increased risk of medullary thyroid cancer among patients with personal or family history of medullary thyroid cancer or MEN2
|
| Phentermine-topiramate | - This combination medication is approved for weight loss in patients ≥12 years
- Phentermine is a sympathomimetic stimulant
- Topiramate has multiple mechanisms of action and is also an anticonvulsant
- Both drugs are centrally acting and suppress appetite
| - Starting dose – 3.75 mg/23 mg orally once daily
- Mid-dose – 7.5 mg/46 mg orally once daily
- High dose – 15 mg/92 mg orally once daily
- Refer to clinical drug reference or prescribing information for titration
| - High dose – Mean weight loss 15.8 kg; BMI loss 5.3 kg/m2 (10%)[4]
- Mid-dose – Mean weight loss 12.1 kg; BMI loss 5.3 kg/m2 (8.1%)[4]
| - Phentermine has sympathomimetic side effects (dose dependent)
- Topiramate may have neuropsychiatric side effects including cognitive slowing; withdrawal may cause seizures; must taper to discontinue
- Contraindicated in pregnancy (increased risk of orofacial clefts)
|
| Setmelanotide | - Approved for weight loss in individuals ≥6 years of age with POMC deficiency, PCSK1 deficiency, LEPR deficiency confirmed by genetic testing, or Bardet-Biedl syndrome
- Specifically targets the MC4R pathway, including leptin signaling
| - Starting dose is 1 to 2 mg subcutaneously once daily depending on patient age; may titrate based on response and tolerability
- Maximum dose 3 mg once daily
| - From small open-label studies ages ≥6 years:
- POMC or PCSK1 – Mean weight loss 23.1 kg; 80% achieved at least 10% weight loss[5]
- LEPR – Mean weight loss 9.7 kg; 46% achieved at least 10% weight loss[5]
- Bardet-Biedl syndrome – Mean BMI loss 7.9 kg/m2; 39% achieved at least 10% decrease in BMI[6]
| - Injection site reaction
- Nausea
- Skin hyperpigmentation
|
| Moderate efficacy |
| Phentermine (as monotherapy) | - Approved for 16 years and older and for short-term use only (3 months; United States)
- Limited safety and efficacy data for longer-term use (and only in adults)[7]
- Sympathomimetic stimulant
| - Capsule (15 mg, 30 mg, or 37.5 mg) or tablet (37.5 mg) – 15 to 37.5 mg orally once daily or 18.75 mg (one-half tablet) 1 to 2 times daily
- Tablet (8 mg) – 4 to 8 mg orally 3 times daily
| - Observational studies:
- In adults – Weight decrease 6 to 8% at 6 and 12 months[7]; early response correlated with efficacy
- In children – Weight decrease 3.2 kg, BMI decrease 4% at 6 months[8]
- Higher doses are associated with increased adverse effects but not necessarily increased efficacy
| - Side effects (dose dependent):
- Elevated BP
- Increased heart rate
- Dizziness
- Headache
- Tremor
- Dry mouth
- Abdominal pain
- Constipation
- Nervousness
|
| Low efficacy |
| Lisdexamfetamine | - Not approved for weight management
- Approved for treatment of BED (adults) or for ADHD (ages 6 years and older)
- Stimulant
| - Starting dose is 20 to 30 mg orally in the morning; may increase dose in increments of 10 mg/day
- No clear effective dose for BMI reduction
| - Limited evidence for weight loss:
- Adults with BED – Mean 6% weight loss[9]
| - Elevated BP
- Insomnia
- Irritability
|
| Metformin | - 10 years and older (for T2DM)
- Inhibits hepatic gluconeogenesis; increases peripheral tissue uptake of glucose
| - Recommended starting dose is 500 mg orally 1 or 2 times daily
- Gradual increase up to 2000 mg
- Extended release recommended for fewer side effects
| - Meta-analysis in children – Mean BMI decrease 0.86 kg/m2 after 6-12 months[10]
- Use for weight loss in children without T2DM is questionable due to low efficacy
| - Lactic acidosis (rare but serious)
- Side effects are dose dependent and include bloating, nausea, flatulence, and diarrhea
|
| Orlistat | - 12 years and older
- Intraluminal inhibitor of pancreatic and gastric lipase; causes fat malabsorption
| - 120 mg orally 3 times per day with each fat-containing meal
| - Meta-analysis in children – Mean BMI decrease 0.79 kg/m2 after 6-12 months[11]
| - Steatorrhea
- Fecal urgency
- Flatulence
- Decreased absorption of fat-soluble vitamins
|
