Table 2.
Summary of Anti-Obesity Medications. All anti-obesity medications are contraindicated in patients with hypersensitivity to the drug (e.g., anaphylaxis, angioedema), should not be used in patients planning to become pregnant or who are pregnant, and all may require downward dose adjustment of concomitant anti-diabetes medication to avoid hypoglycemia, especially in patients treated with insulin and sulfonylureas.
| Drug | Description | Main Side Effects | Illustrative Drug Interactions |
|---|---|---|---|
| Phentermine∗ [[37], [38], [39], [40], [41]] | Sympathomimetic amine approved as a weight management medication in 1959. It is a DEA Schedule IV stimulant agent approved for short-term use (12 weeks). Approved for age 17 years or older. Average weight reduction is about 3–8%.∗ | Side effects include headache, high blood pressure, rapid or irregular heart rate, overstimulation, tremor, dry mouth, and insomnia. Contraindicated in patients with cardiovascular disease, stroke, uncontrolled hypertension, within 14 days of monoamine oxidase inhibitors, hyperthyroidism, glaucoma, agitated states, or with a history of drug abuse. | May have interactions with other sympathomimetics, alcohol, adrenergic neuron blocking drugs, and possibly some anesthetic agents. Should not be taken during or within 14 days following monoamine oxidase (MAO) inhibitors. |
| Semaglutide∗∗ [42,43] | Glucagon-like peptide-1 receptor agonist that at lower injectable doses 0.25–2.0 mg per week, and at oral doses of 7–14 mg per day, is indicated to lower blood sugar in patients with type 2 diabetes mellitus. Semaglutide at 2.4 mg subcutaneously per week is approved for treatment of obesity. Average weight reduction is about 15%. |
Adverse reactions include nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation (belching), flatulence, gastroenteritis, and gastroesophageal reflux disease. Contraindicated in patients with personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2 or known hypersensitivity to semaglutide. Warnings and precautions: acute pancreatitis, acute gallbladder disease, acute kidney injury especially in patients with severe adverse gastrointestinal reactions, diabetes retinopathy, heart rate increase, suicidal behavior and ideations. Associated with hypoglycemia in patients with type 2 diabetes treated with concomitant hypoglycemic medications such as sulfonylureas or insulin. |
May slow gastric emptying, which may impact absorption of concomitantly administered oral medication. |
| Liraglutide∗∗ [14,15,44] | Glucagon-like peptide-1 receptor agonist that is an injectable drug. At lower doses (1.8 mg per day), liraglutide is indicated to lower blood sugar among patients with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease. Liraglutide 3.0 mg per day is approved for treatment of obesity. Average weight reduction is 5–10%, especially with the liraglutide higher dose. Approved for patients 12 years or older. | Adverse reactions include nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal insufficiency. Contraindicated with personal or family history or medullary thyroid cancer or Type 2 Multiple Endocrine Neoplasia syndrome. Discontinue with suspected pancreatitis, gall bladder disease, or suicidal behavior and ideation. May promote hypoglycemia, particularly in patients with diabetes mellitus treated with insulin or sulfonylureas. | May slow gastric emptying, which may impact absorption of concomitantly administered oral medication. |
| Phentermine/topiramate [44,45] | Combination of phentermine (sympathomimetic amine, anti-obesity medication) and topiramate (used to treat seizures and migraine headaches) that is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management. DEA Schedule IV drug. Average weight reduction is 5–10%. | Can cause paresthesia (tingling or numb feelings to extremities), dizziness, dysgeusia (abnormal taste), insomnia, constipation, or dry mouth. Monitor for increased heart rate, suicidal behavior/ideation, mood and sleep disorders, cognitive impairment, metabolic acidosis, elevated creatinine, and low blood sugars in patients on anti-diabetes medications. Discontinue with acute myopia and secondary angle glaucoma. Should not be used in patients with glaucoma or hyperthyroidism. Topiramate can cause birth defects. Phentermine/topiramate should not be started until after a pregnancy test is negative. Thereafter, the FDA recommends women use effective contraception and have monthly pregnancy tests during treatment with phentermine/topiramate. (https://qsymiarems.com/) | Should not be taken during or within 14 days of monoamine oxidase inhibitors. Avoid use with alcohol, due to potentiation of depressant effects. May potentiate hypokalemia when used with non-potassium sparing diuretics. May alter hormone exposure with oral contraceptives but may not increase risk of pregnancy. |
| Naltrexone/bupropion [17,44,46,47] | Combination of naltrexone (opioid antagonist used for addictions) and bupropion (used for depression and smoking cessation) that is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management. Average weight reduction is about 5%. | Naltrexone/bupropion can cause nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea, and acute angle closure glaucoma. The bupropion component is marketed as an antidepressant, and antidepressants can increase the risk of suicidal thinking in children, adolescents, and young adults; monitor for suicidal thoughts and behaviors. Should not be used in patients with uncontrolled high blood pressure, seizure disorders, or drug/alcohol withdrawal. | May have drug interactions with opioid medications, anti-seizure medications, MAO inhibitors, and other drugs. Should not be taken with other bupropion or naltrexone-containing medications. Central nervous system toxicity can occur when used concomitantly with dopaminergic drugs (e.g., levodopa and amantadine). |
| Orlistat [44,48] | Gastrointestinal lipase inhibitor (i.e., impairs digestion of dietary fat) that is indicated for obesity management, including weight reduction and weight management in conjunction with a reduced-calorie diet, and for reduced risk of weight regain after weight reduction. Lower doses are approved over-the-counter. Average weight reduction is 5% of body weight. Approved for patients 12 years or older. | Side effects include oily discharge with flatus from the rectum, fecal urgency, and increased defecation and fecal incontinence, especially after fatty food intake. (May help with constipation.) May promote gallstones and kidney stones. May cause malabsorption of fat-soluble vitamins (A, D, E, K). Need to take a multivitamin daily. Contraindicated in chronic malabsorption syndrome and cholestasis. Rare cases of severe liver injury and pancreatitis. |
Cyclosporine, hormone contraceptives, seizure medications, thyroid hormones, warfarin |
∗Phentermine weight reduction efficacy reported in the medical literature depends on when and where the data were derived. The data listed for the anti-obesity agents in this table are derived from controlled trials. From the perspective of prospective controlled clinical trials, the placebo-corrected phentermine weight reduction is about 3–8% [[37], [38], [39], [40]]. In a meta-analysis of phentermine monotherapy clinical trials, the placebo-corrected reduction in body weight with phentermine was less than 4 kg [49]. Conversely, from the perspective of retrospective medical chart reviews (without placebo control), the weight reduction efficacy of phentermine is reported to range from 4% to 19% among patients commonly treated with phentermine doses of 60 mg per day (and thus doses higher than approved by the FDA) [50,51], with reports that some clinicians are known to prescribe phentermine doses as high as 112 mg per day [52].
∗∗Glucagon-like peptide-1 receptor agonists (GLP-1 RA) slow gastric emptying. Many patients with obesity have type 2 diabetes mellitus. If patients treated with GLP-1 RA develop signs, symptoms, and/or diagnostic evidence of gastroparesis, then this may prompt the clinician to discontinue the GLP-1 RA, before assuming the gastroparesis is due to diabetes mellitus neuropathy [53].
∗∗Calcitonin is a polypeptide secreted by thyroid C-cells that is involved with bone and calcium metabolism. Medullary thyroid cancer is often associated with marked elevations in calcitonin (>100 pg/mL) [54,55]. The prescribing informations for approved GLP-1 RAs do not recommend routine monitoring of calcitonin blood levels. Healthy human thyroid C cells do not express GLP 1 receptors [56]. Especially at marginal to mild elevations in calcitonin blood levels, hypercalcitoninemia is not pathognomonic of medullary thyroid cancer. Some reports suggest that mild elevation in calcitonin levels can be due to thyroid disease other than medullary thyroid cancer [54]. Especially in the absence of family history otherwise suggesting genetic predisposition to medullary thyroid cancer, and especially in the absence of abnormal thyroid gland physical findings (i.e., nodules or goiter), modestly elevated calcitonin levels are more likely due to other non-thyroid causes, such as neuroendocrine tumors [54]. Examples of common drugs that may increase calcitonin include omeprazole and other proton pump inhibitors, glucocorticoids, beta-blockers, and glucagon [54]. Calcitonin levels may also increase in patients with chronic renal disease [57].