Version July 2025
| Generic name | Usual dosing (adults) | US DEA schedule | Adverse effects and precautions* |
| Dual GLP-1 and GIP receptor agonist approved for long-term use | |||
| Tirzepatide | Initial: 2.5 mg subcutaneously once weekly. Increase dose by 2.5 mg at minimum of 4-week intervals. Recommended maintenance doses are 5 to 15 mg once weekly. If increased dose is not tolerated, down titrate and consider delaying dose escalation.¶ | Not a controlled substance | Nausea, vomiting, diarrhea, constipation, hypoglycemia in patients with T2DM (more common if used in conjunction with diabetes medications known to cause hypoglycemia), injection site reactions, increased lipase, increased heart rate. Rarely reported: pancreatitis, gallbladder disease, acute kidney injury, suicidal thoughts, serious hypersensitivity reactions (eg, anaphylaxis, angioedema). Causes a modest delay of gastric emptying. Patients undergoing elective surgery or procedures involving anesthesia may need to hold tirzepatide prior to surgery. Advise patients to avoid dehydration in relation to GI side effects. Monitor blood glucose in patients with diabetes and adjust coadministered insulin, sulfonylureas (eg, reduce dose by 50%), and other diabetes medications as needed to prevent potentially severe hypoglycemia. Possible increase in thyroid cancer risk based on rodent studies. Contraindicated in pregnancy and in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B. Avoid in patients with severe inflammatory bowel disease or gastroparesis. Use caution in those with a history of pancreatitis. Monitor patients with diabetic retinopathy for eye complications. |
| GLP-1 agonists approved for long-term use | |||
| Semaglutide | Initial: 0.25 mg subcutaneously once weekly. Increase dose at 4-week intervals (ie, to 0.5, 1, 1.7, then 2.4 mg) until recommended maintenance dose of 2.4 mg once weekly. If increased dose is not tolerated, consider delaying dose escalation by 4 weeks. Alternate maintenance dose of 1.7 mg once weekly can be used for patients unable to tolerate 2.4 mg dose. | Not a controlled substance | Nausea, vomiting, diarrhea, constipation, hypoglycemia in patients with T2DM (more common if used in conjunction with diabetes medications known to cause hypoglycemia), injection site reactions, increased lipase, increased heart rate. Rarely reported: pancreatitis, gallbladder disease, acute kidney injury, suicidal thoughts, serious hypersensitivity reactions (eg, anaphylaxis, angioedema). Causes a modest delay of gastric emptying. Patients undergoing elective surgery or procedures involving anesthesia may need to hold medication prior to surgery. Advise patients to avoid dehydration in relation to GI side effects. Monitor blood glucose in patients with diabetes and adjust coadministered insulin, sulfonylureas (eg, reduce dose by 50%), and other diabetes medications as needed to prevent potentially severe hypoglycemia. Possible increase in thyroid cancer risk based on rodent studies. Contraindicated in pregnancy and in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2B. Avoid in patients with severe inflammatory bowel disease or gastroparesis. Use caution in those with a history of pancreatitis. For semaglutide, monitor patients with diabetic retinopathy for eye complications. |
| Liraglutide | Initial: 0.6 mg subcutaneously once daily. Increase daily dose by 0.6 mg at weekly intervals until recommended maintenance dose of 3 mg once daily. If increased dose is not tolerated, consider delaying dose escalation by an additional week.Δ | Not a controlled substance | |
| Combination phentermine-topiramate approved for long-term use | |||
| Phentermine-topiramate | Initial: 3.75 mg phentermine/23 mg topiramate once daily in the morning for 14 days, followed by 7.5 mg phentermine/46 mg topiramate once daily for 12 weeks. If weight loss ≥3% has not been achieved, the dose may be further increased to 11.25 mg phentermine/69 mg topiramate daily for 14 days and then to a maximum dose of 15 mg phentermine/92 mg topiramate once daily.◊ | C-IV (due to phentermine component) | Dry mouth, taste disturbance, constipation, paresthesias, depression, anxiety, elevated heart rate, cognitive disturbances, insomnia (higher dose). Abuse potential due to phentermine component. Topiramate is teratogenic (increased risk of oral cleft defects, fetal growth restriction); individuals of child-bearing potential should have a negative pregnancy test prior to and monthly during treatment and must use reliable contraception. Actions of topiramate component include inhibition of carbonic anhydrase; rarely, metabolic acidosis and kidney stones may result from renal bicarbonate loss. Upon discontinuation, tapering of dose over at least 1 week using every-other-day dosing is recommended. Contraindicated with pregnancy, breastfeeding, hyperthyroidism, glaucoma, or within 14 days of MAO inhibitors. |
| Combination naltrexone-bupropion approved for long-term use | |||
| Naltrexone-bupropion | Week 1: 1 tablet (8 mg naltrexone/90 mg bupropion) once daily. Week 2: 1 tablet twice daily. Week 3: 2 tablets in the morning and 1 tablet in the evening. Week 4: 2 tablets twice daily. Maximum daily dose: 4 tablets (32 mg naltrexone/360 mg bupropion). | Not a controlled substance | Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth. Transient increase in blood pressure (1 to 2 mmHg on average) during initial 12 weeks of treatment; heart rate may also be increased. Contraindicated in patients with uncontrolled hypertension, seizure disorder, eating disorder, use of other bupropion-containing products, chronic opioid use, pregnancy, breastfeeding, or within 14 days of MAO inhibitors.§ |
| Pancreatic lipase inhibitor approved for long-term use | |||
| Orlistat | 120 mg 3 times daily with fat-containing meals. A reduced dose of 60 mg¥ is an option for patients who do not tolerate 120 mg. | Not a controlled substance | Cramps, flatulence, fecal incontinence, oily spotting. Absorption of fat-soluble vitamins may be reduced. Rarely reported: severe liver injury, oxalate-kidney injury. Contraindicated during pregnancy and in patients with chronic malabsorption or cholestasis; generally avoid in patients with history of oxalate-induced kidney stones. |
| Noradrenergic sympathomimetic drugs approved for short-term use | |||
| Benzphetamine | Initial: 25 mg once daily; may increase up to 50 mg 3 times daily if needed and tolerated. Maximum dose: 50 mg 3 times daily. | C-III | Applies to all sympathomimetic agents:
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| Diethylpropion | Immediate release: 25 mg 3 times daily, 1 hour before meals. Controlled release: 75 mg once daily in the morning. | C-IV | |
| Phentermine | Immediate release (Adipex-P and generics): 15 to 18.75 mg once daily or 30 to 37.5 mg in 1 or 2 divided doses. Immediate release (Lomaira): 8 mg 3 times daily before meals. | C-IV | |
| Phendimetrazine | Immediate release: 17.5 to 35 mg 2 or 3 times daily, 1 hour before meals; may increase to 70 mg 3 times daily if needed and tolerated. Maximum dose: 70 mg 3 times daily. Sustained release: 105 mg once daily in the morning. | C-III | |
CVD: cardiovascular disease (arrhythmias, congestive heart failure, coronary artery disease, stroke, uncontrolled hypertension); FDA: US Food and Drug Administration; GI: gastrointestinal; GIP: gastric inhibitory polypeptide; GLP-1: glucagon-like peptide 1; MAO inhibitors: monamine oxidase inhibitors; T2DM: type 2 diabetes mellitus; US DEA: United States Drug Enforcement Agency.
* Applies to all drugs except orlistat: May increase risk of hypoglycemia in patients with type 2 diabetes, particularly when used in combination with diabetes medications known to cause hypoglycemia. For additional information on potential interactions of antiobesity drugs with other medications, use the drug interactions program included with UpToDate.
¶ The initial dose of 2.5 mg once weekly is intended to reduce GI symptoms and does not provide effective weight loss.
Δ According to United States labeling, if weight loss is not ≥4% after 16 weeks or 3 mg/day is not tolerated, discontinue use. Labeling in the European Union recommends discontinuation of use if weight loss is not ≥5% after 12 weeks of 3 mg/day.
◊ If weight loss is not ≥5% after 12 weeks of 15 mg phentermine/92 mg topiramate once daily, discontinue use (ie, with taper).
§ FDA recommends warning young adults (age 18 to 24 years) of the risk of developing suicidality during initial treatment of psychiatric disorders with any antidepressant (eg, bupropion).
¥ Orlistat 60 mg is available without a prescription in the United States and some other countries.
