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Drug and class Ideal candidates Adverse effects Contraindicationsa Average wholesale priceb Liraglutide Semaglutide (GLP-1 receptor agonist) Patients with coronary artery disease, prediabetes, and diabetes Constipation, diarrhea, nausea, headache, fatigue, and injection site reactions. Serious but rare: increased heart rate, renal impairment, pancreatitis, and suicidal ideation. Potential risk of thyroid C-cell tumor.
Semaglutide is associated with an increased incidence of diabetic retinopathy complications, probably attributable to rapid correction of hyperglycemia in patients with diabetes.Family or personal history of medullary thyroid cancer or multiple endocrine neoplasia type 2. Use with caution in patients with severe chronic kidney disease and history of pancreatitis. Liraglutide $1,619
Semaglutide $1,022Naltrexone-bupropion (opioid receptor antagonist and DNRI) Patients with depression, those interested in smoking cessation, and those with food addiction and strong cravings Glaucoma, hepatotoxicity, increase in heart rate and blood pressure, headache, nausea, constipation, vomiting, dry mouth. Serious but rare: suicidal ideation and a lower seizure threshold. Uncontrolled hypertension, seizures, anorexia, bulimia, drug or alcohol withdrawal, or chronic opioid use. $365 Orlistat (lipase inhibitor) Patients who do not want to take a systemic drug, or patients who eat a moderate- or high-fat diet Headaches, flatulence, cramping, fecal incontinence, oily spotting, decreased absorption of medications and fat-soluble vitamins. Gastric disturbances can be reduced by taking with psyllium. Serious but infrequent: liver injury, cholelithiasis, nephrolithiasis. None, but not recommended for patients with malabsorption (eg, after gastric bypass surgery). $108 Phentermine-topiramate ERc (sympathomimetic amine and GABA receptor modulator) Patients with chronic migraines Increased heart rate, dizziness, neuropathy, insomnia, anxiety, depression, cognitive impairment, and dry mouth. Serious but rare: suicidal ideation, acidosis, hypokalemia, rise in serum creatinine, myopia, or glaucoma. Minimal risk of seizures with rapid discontinuation. Uncontrolled anxiety or depression, cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, and history of substance dependence. $239 ↵a All antiobesity medications are contraindicated in pregnancy. Because of potential teratogenicity of many antiobesity drugs, a pregnancy test should be done before prescribing, and women should be counseled on effective birth control.
↵b Lexicomp average wholesale price for 30-day supply of maximum doses as of May 2021.
↵c A controlled substance.
DNRI = dopamine-norepinephrine reuptake inhibitor; ER = extended release; GABA = gamma aminobutyric acid; GLP-1 = glucagon-like protein-1
Drug and class Ideal candidates Side effects Contraindicationsa Average wholesale priceb Lisdexam-fetaminec (amphetamine prodrug) Patients with attention deficit hyperactivity disorder Insomnia, irritability, anxiety, dry mouth, increased heart rate and blood pressure. Controlled substance with theoretical potential for abuse and dependence. None, but we recommend against using in patients with cardiovascular disease. $402 Phentermined (sympathomimetic amine) N/A Headaches, increased blood pressure and heart rate, irritability, insomnia, constipation, diarrhea, impotence, dizziness. Controlled substance with theoretical potential for abuse and dependence. Serious but rare: pulmonary hypertension, valvular disease. Uncontrolled anxiety and hypertension, cardiovascular disease, hyperparathyroidism, glaucoma, and history of drug dependence. $21.30 Topiramatee (GABA receptor modulator) Patients with chronic migraines Insomnia, xerostomia, constipation, paresthesias, dizziness, anxiety, depression, drowsiness, language and memory impairments. Very rare: seizures with rapid discontinuation. Hyperthyroidism, glaucoma. $10 Metformine,f (biguanide) Patients with diabetes and prediabetes Diarrhea, nausea, abdominal pain. Serious but rare: lactic acidosis. Severe chronic kidney disease. $5 Pramlintidee,f (amylin analogue) Patients with type 1 or type 2 diabetes Hypoglycemia, headaches, nausea, vomiting. Gastroparesis and hypoglycemic unawareness. $694 SGLT-2 inhibitorse,f Patients with type 2 diabetes, hypertension, heart failure, cardiovascular disease, diabetic kidney disease Genitourinary infections, hypovolemia, increased low-density lipoprotein cholesterol, and hyperkalemia. Serious but rare: diabetic ketoacidosis, bone fractures, amputations, Fournier gangrene. Severe chronic kidney disease and ketogenic diet (concern for euglycemic ketoacidosis). $600-$700 ↵a All antiobesity medications are contraindicated in pregnancy except for metformin in patients with diabetes. Because of the potential teratogenic effect of many antiobesity medications, a pregnancy test should be obtained before prescribing, and women should be counseled on effective birth control.
↵b Lexicomp average wholesale price for 30-day supply of maximum doses as of May 2021.
↵c Approved for treatment of binge-eating disorder.
↵d Approved for short-term use; however, it is often prescribed long-term in US states where this regulation is not strictly enforced.
↵e Off-label use.
↵f Occasionally prescribed for patients who do not have diabetes or another US Food and Drug Administration indication for their use; however, this is not our practice.
GABA = gamma aminobutyric acid; SGLT-2 = sodium-glucose cotransporter-2
Medication Patients Dose % TBWL vs placebo Liraglutide10 Diabetes, body mass index (BMI) ≥ 27 kg/m2 1.8 mg
3.0 mg2.7
4.0Liraglutide11 Prediabetes, BMI ≥ 30 or ≥ 27 with hypertension or dyslipidemia 3.0 mg 5.4 Liraglutide12 No diabetes, BMI ≥ 30 or ≥ 27 with hypertension or dyslipidemia, who lost ≥ 5% total body weight with a low-calorie diet 3.0 mg 6.0 Naltrexone-bupropion13 Diabetes, BMI ≥ 27 32/360 mg 3.2 Naltrexone-bupropion14 No diabetes, BMI ≥ 30 or ≥ 27 with hypertension or dyslipidemia 16/360 mg
32/360 mg3.7
4.8Naltrexone-bupropion15 No diabetes, BMI ≥ 30 or ≥ 27 with hypertension or dyslipidemia 32/360 mg 5.2 Naltrexone-bupropion16 No diabetes, BMI ≥ 30 or ≥ 27 with hypertension or dyslipidemia 32/360 mg 4.2 Orlistat17 BMI 30–43 120 mg TID 3.0 Orlistat18 BMI 30–44 120 mg TID 3.7 Orlistat19 Type 2 diabetes, clinically stable on oral sulfonylureas, BMI 28–40 120 mg TID 1.9 Phentermine-topiramate ER20 No diabetes, BMI ≥ 35, blood pressure ≤ 140/90 mm Hg 3.75/23 mg
15/92 mg3.5
9.3Phentermine-topiramate ER21 BMI 27–45 with at least 2 of the following: hypertension, dyslipidemia, diabetes, prediabetes, abdominal obesity 7.5/46 mg
15/92 mg8.0
10.8Phentermine-topiramate ER22 BMI 27–45 with at least 2 of the following: hypertension, dyslipidemia, diabetes, prediabetes, abdominal obesity 7.5/46 mg
15/92 mg7.1
8.5Phentermine-topiramate ER23 BMI 30–45 7.5/46 mg
15/92 mg6.8
7.5Lisdexamfetamine24 Adults with binge eating disorder, BMI 25–45 30 mg
50 mg
70 mg3.3
5.2
5.3Phentermine23 BMI 30–45 7.5 mg
15 mg3.7
4.4Topiramate23 BMI 30–45 46 mg
92 mg3.4
4.7Metformin25 No diabetes, BMI ≥ 24 (≥ 22 in Asian Americans), elevated fasting glucose or impaired glucose tolerance 850 mg BID 2.3 Pramlintide26 No diabetes, BMI 30–50 120 μg TID
360 μg TID5.6
6.8Canagliflozin27
Semaglutide10
Semaglutide11No diabetes, BMI 27–50
No diabetes, BMI ≥ 30, or ≥ 27 with at least 1 obesity-associated comorbidity
Diabetes, BMI ≥ 2750 mg
100 mg
300 mg
2.4 mg/week
2.4 mg/week0.9
1.6
1.4
12.4
6.2BID = twice a day; ER = extended release; TID = three times a day; TBWL = total body weight loss