Table 6.5-3. Summary of common pharmacologic agents for obesity

Availability

Mechanism of action

Dose

Common adverse events and contraindications

Efficacy in kg/% of body weight loss (1 year, placebo subtracted, ITT population)

Orlistat

US (FDA has approved orlistat for children aged ≥12 years), Canada, Europe

GI lipase inhibitor (decreases fat absorption)

120 mg PO tid with meals

GI: oily spotting, gas with discharge, fecal urgency, fatty or oily stools, increased defecation, fecal incontinence

~3%

Phentermine/topiramate

US

Amphetamine analogue/anticonvulsant

3.75/23 mg to 15/92 mg PO daily

Xerostomia, paresthesia, insomnia, constipation, dysgeusia, and dizziness; contraindicated in patients with glaucoma, hyperthyroidism, concomitant use of MAOIs; known hypersensitivity or idiosyncrasy to the sympathomimetic amines

6.7 kg/6.6% (dose, 7.5/46 mg)

8.8 kg/8.6% (dose, 15/92 mg)

Liraglutide (3.0 mg/d)

US, Canada, Europe

GLP-1 receptor agonist (increases satiety, delays gastric emptying, decreases food reward)

0.6 mg/d SC, increase by 0.6 mg/wk until target dose of 3.0 mg/d SC is reached

Nausea, diarrhea, constipation, vomiting and headache; contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, MEN 3, or pancreatitis

4%-5.4%

Semaglutide (2.4 mg/wk) SC

US, Canada/Europe

GLP-1 receptor agonist (increases satiety, delays gastric emptying, decreases food reward)

Weekly SC injections: 0.25 mg for 4 weeks, 0.5 mg for 4 weeks, 1.0 mg for 4 weeks, 1.7 mg for 4 weeks; target dose: 2.4 mg SC/wk

Nausea, diarrhea, constipation, vomiting and headache; contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, MEN 3, or pancreatitis

12.5%

Tirzepatide

US, approved only for type 2 diabetes in Canada and Europe

Dual GIP/GLP-1 receptor agonist (increases satiety, delays gastric emptying, decreases food reward)

Weekly SC injection, 3 therapeutic doses: 5 mg, 10 mg, 15 mg

Start at 2.5 mg/wk and increase by 2.5 mg every 4 weeks until therapeutic dose is reached

Nausea, diarrhea, constipation, vomiting and headache; contraindicated in patients with a personal or family history of MTC or in patients with MEN 2, MEN 3, or pancreatitis

11.9% (5 mg dose), 16.4% (10 mg dose), 17.8% (15 mg dose)

Naltrexone HCl/bupropion HCl

US, Canada, Europe

Opioid receptor antagonist/dopamine and norepinephrine reuptake inhibitor (decreases cravings from the mesolimbic reward system and hunger)

8/90 mg/d (1 tablet) PO, increase by 1 tablet/wk until target dose of 2 tablets PO bid is reached

Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea; contraindicated in uncontrolled hypertension, seizure disorders, patients using other bupropion-containing products, in bulimia or anorexia nervosa (increases the risk of seizures), chronic opioid use, abrupt discontinuation of alcohol intake, with benzodiazepines, barbiturates, antiepileptic drugs, and MAOIs

3.3%-4.8%

bid, 2 times a day; FDA, Food and Drug Administration; GI, gastrointestinal; GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide 1; ITT, intention to treat; MAOIs, monoamine oxidase inhibitors; MEN 2, multiple endocrine neoplasia type 2; MEN 3, multiple endocrine neoplasia type 3; MTC, medullary thyroid cancer; PO, oral; SC, subcutaneous; tid, 3 times a day.