Antiobesity drug therapy: An individualized and comprehensive approach

Yael Mauer; Marcie Parker; Sangeeta R. Kashyap

doi:10.3949/ccjm.88a.20080

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TABLE 1

Drugs approved for long-term treatment of obesity

Drug and class	Ideal candidates	Adverse effects	Contraindications^{^a}	Average wholesale price^{^b}
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 $1,022
Naltrexone-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 ER^{^c} (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

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TABLE 2

Other drugs used for treating obesity

Drug and class	Ideal candidates	Side effects	Contraindications^{^a}	Average wholesale price^{^b}
Lisdexam-fetamine^{^c} (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
Phentermine^{^d} (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
Topiramate^{^e} (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
Metformin^{^e,^f} (biguanide)	Patients with diabetes and prediabetes	Diarrhea, nausea, abdominal pain. Serious but rare: lactic acidosis.	Severe chronic kidney disease.	$5
Pramlintide^{^e,^f} (amylin analogue)	Patients with type 1 or type 2 diabetes	Hypoglycemia, headaches, nausea, vomiting.	Gastroparesis and hypoglycemic unawareness.	$694
SGLT-2 inhibitors^{^e,^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

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TABLE 3

Weight loss in randomized, double-blind, placebo-controlled trials

Medication	Patients	Dose	% TBWL vs placebo
Liraglutide¹⁰	Diabetes, body mass index (BMI) ≥ 27 kg/m²	1.8 mg 3.0 mg	2.7 4.0
Liraglutide¹¹	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 mg	3.7 4.8
Naltrexone-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 mg	3.5 9.3
Phentermine-topiramate ER²¹	BMI 27–45 with at least 2 of the following: hypertension, dyslipidemia, diabetes, prediabetes, abdominal obesity	7.5/46 mg 15/92 mg	8.0 10.8
Phentermine-topiramate ER²²	BMI 27–45 with at least 2 of the following: hypertension, dyslipidemia, diabetes, prediabetes, abdominal obesity	7.5/46 mg 15/92 mg	7.1 8.5
Phentermine-topiramate ER²³	BMI 30–45	7.5/46 mg 15/92 mg	6.8 7.5
Lisdexamfetamine²⁴	Adults with binge eating disorder, BMI 25–45	30 mg 50 mg 70 mg	3.3 5.2 5.3
Phentermine²³	BMI 30–45	7.5 mg 15 mg	3.7 4.4
Topiramate²³	BMI 30–45	46 mg 92 mg	3.4 4.7
Metformin²⁵	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 TID	5.6 6.8
Canagliflozin²⁷ Semaglutide¹⁰ Semaglutide¹¹	No diabetes, BMI 27–50 No diabetes, BMI ≥ 30, or ≥ 27 with at least 1 obesity-associated comorbidity Diabetes, BMI ≥ 27	50 mg 100 mg 300 mg 2.4 mg/week 2.4 mg/week	0.9 1.6 1.4 12.4 6.2