Table 1
Incretin-based therapies. All listed medications are contraindicated in pregnancy and are best avoided in women who are pregnant, trying to become pregnant, or are breastfeeding. MEN2A: multiple endocrine neoplasia syndrome type 2; OR: odds ratio
| DRUG NAME | INDICATIONS | PRIMARY MECHANISM | MEAN WEIGHT LOSS | SIDE EFFECTS | CONTRAINDICATIONS | SPECIAL CONSIDERATIONS | PRICING OPTIONS* |
|---|---|---|---|---|---|---|---|
| Liraglutide (Saxenda) | Indicated in patients with BMI ≥ 30 kg/m2, or in patients with a BMI ≥ 27 kg/m2 and at least one weight-related comorbidity in conjunction with diet and physical activity | GLP-1 receptor agonist | 8% | Nausea (39%), diarrhea (21%), vomiting (16%), constipation (19%), headache (14%), dyspepsia (10%) | Personal or family history of medullary thyroid carcinoma, or MEN2A syndrome | Acute pancreatitis (OR 0.65-1.34), gallbladder disease (OR 1.23-1.52) diabetic retinopathy (OR 0.11-1.03) | $$ Discount/coupon available online No generic alternatives |
| Semaglutide (Wegovy) | 14.9% | Nausea (44%), diarrhea (30%), vomiting (24%), constipation (24%), abdominal pain (20%), headache (14%), fatigue (10%) | $$ Discount/coupon available online No generic alternatives | ||||
| Tirzepatide (Zepbound) | GLP-1 and GIP receptor agonist | 20.9% | Nausea (25-29%), diarrhea (19-23%), constipation (11-17%), vomiting (8-13%), abdominal pain (10%), dyspepsia (10%) | $$ Discount/coupon available online No generic alternatives |
[i] *Insurance coverage of individual medications will depend upon individual plan.
Table 2
Non-incretin-based therapies. All above obesity medications are contraindicated in pregnancy and are best avoided in women who are pregnant, trying to become pregnant, or are breastfeeding. POMC: pro-opiomelanocortin; MAOIs: monoamine oxidase inhibitors; CVD: cardiovascular disease; CAD: coronary artery disease; CHF: congestive heart failure; BMI: body mass index; HR: heart rate; MAOI: monoamino oxidase inhibitors; GABA: gamma aminobutyric acid
| DRUG NAME | INDICATIONS | PRIMARY MECHANISM | MEAN WEIGHT LOSS | SIDE EFFECTS | CONTRAINDICATIONS | SPECIAL CONSIDERATIONS | PRICING OPTIONS |
|---|---|---|---|---|---|---|---|
| Orlistat3(Xenical/Alli) Approved 1999 and 2007 OTC | Indicated in patients with BMI ≥ 30 kg/m2, or in patients with a BMI ≥ 27 kg/m2 and at least one weight-related comorbidity in conjunction with diet and physical activity. Also indicated to reduce the risk for weight regain after prior weight loss | Gastrointestinal lipase inhibitor, prevents absorption of ~30% of ingested fat | 10.2% | Oily fecal spotting (27%), flatus with discharge (24%), fecal urgency (22%), steatorrhea (20%), oily discharge (12%), increased defecation (11%) | Chronic malabsorption, cholestasis | May cause malabsorption of other medications | $$ Pharmacy coupon available $ Lower cost over-the-counter option available (Alli) however is half the dose of Xenical with less efficacy |
| Phentermine (Adipex-P)/ Sympathomimetic amines3 Approved 1959 | Short-term adjunct for weight reduction in patients age ≥ 16 with initial body mass index ≥ 30 kg/m2, or ≥ 27 kg/m2 in the presence of other risk factors | Catecholamine release in the hypothalamus | 6.1% | Xerostomia (12%), insomnia (11%), headache (10%) | History of CAD, w/in 14 days of MAOIs, glaucoma, agitated states, substance use disorder | Avoid in CAD, hyperthyroidism, hypertension, seizure | $ Pharmacy coupon available |
| Phenteremine Topiramate ER3 (Qsymia) Approved 2012 | Indicated in patients with BMI ≥ 30 kg/m2, or in patients with a BMI ≥ 27 kg/m2 and at least one weight-related comorbidity in conjunction with diet and physical activity | Phentermine: see above Topiramate: GABA augmentation | 10.9% | Paresthesia (20%), xerostomia (19%), constipation (16%), headache (11% | Same contraindications as phentermine alone in addition to history of CVD (CAD, stroke, arrhythmias, CHF, uncontrolled hypertension) | Avoid in glaucoma and hyperthyroidism Monitor for increased HR, suicidal behavior/ideation, mood/sleep disturbance, cognitive impairment, metabolic acidosis, elevated creatinine, and low blood sugars in in patients on anti-diabetes medication | $ Pharmacy coupon available 12-week supply available direct to consumer for reduced price Can be prescribed as two separate medications for a more cost-effective option |
| Naltrexone Buproprion ER3 (Contrave) Approved 2014 | Chronic obesity management in patients ≥ 18 with a BMI ≥ 30 kg/m2 OR BMI ≥ 27 kg/m2 with at least one weight-related comorbidity | Bupropion: aminoketone antidepressant; POMC neuron stimulation Naltrexone: opioid antagonist | 6.1% | Nausea (33%), constipation (19%), headache (18%), vomiting (11%), dizziness (10%) | Uncontrolled hypertension, seizure disorders, drug/alcohol withdrawal | Monitor for suicidal ideation | $$ No generic alternatives available direct to consumer for reduced price Can be prescribed as two separate medications for a more cost effective option |
| Gelesis100 [32] (Plenity, Gelesis) Approved 2019 | Overweight and obese adults with a BMI of 25-40 kg/m2, when used in conjunction with diet and exercise | Cellulose-citric acid which expands to occupy 25% of stomach volume | 6.4% | Diarrhea (12.6%), abdominal distention (11.7%), infrequent bowel movements (9.4%) and flatulence (8.5%) | Esophageal anatomic anomalies, and complications from prior gastrointestinal (GI) surgery that could affect GI transit and motility | Use with caution in patients with active gastrointestinal conditions such as gastro-esophageal reflux disease, ulcers, or heartburn May cause malabsorption of concomitantly taken medications | $ Pharmacy coupon available No generic options available |
[i] *Insurance coverage of individual medications will depend upon individual plan.
Table 3
Drugs under investigation for the management of obesity. GCGR: glucagon receptor; GIP: glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide 1; BMI: body mass index
| DRUG CLASS | INTERVENTION | MEAN WEIGHT LOSS* | SIDE EFFECTS* | TRIAL |
|---|---|---|---|---|
| GLP-1 / GIP / GCGR agonist | Retatrutide, 1 to 12 mg once weekly for 26 weeks. | 17.5% | Nausea (27%), decreased appetite (18%), diarrhea (13%), vomiting (10%), constipation (9%) | NCT04881760 |
| Melanocortin-4 receptor agonist | Setmelanotide 1 to 3 mg once daily for 16 weeks. | 15% BMI reduction | Nausea (61%), vomiting (33%), skin hyperpigmentation (33%), diarrhea (22%), abdominal pain (17%) | NCT04725240 |
| Non-peptide oral GLP-1 receptor agonist | Orforglipron 12 to 45 mg daily for 26 weeks. | 12.6% | Nausea (42%), vomiting (29%), constipation (19%), diarrhea (16%), GERD (13%) | NCT05051579 |
| Long-acting amylin receptor agonist | Cagrilintide 0.3 to 4.5 mg weekly for 26 weeks. | 10.8% | Nausea (47%), constipation (21%) fatigue (20%), injection-site erythema (17%), vomiting (8%) | NCT03856047 |
| Activin receptor type 2b monoclonal antibody | Bimagrumab 10 mg/kg every 4 weeks for 48 weeks. | 6.5% | Diarrhea (41%), muscle spasms (41%), nausea (11%), lipase elevation (11%), hypertension (8%) | NCT03005288 |
[i] *With highest intervention drug dose
Figure 1
Appetite and energy expenditure regulation in obesity. Leptin, released by the arcuate nucleus neurons in the hypothalamus, induces α-MSH release, which stimulates MC4R, resulting in decreased appetite, increased nonshivering thermogenesis, and energy expenditure. Glucagon activates the leptin-melanocortin pathway. AgRP opposes the leptin-melanocortin pathway. GLP-1 and GIP cause decreased gastric emptying and stimulate insulin secretion. Created in BioRender by Calderon A; (2024) BioRender.com/a11c077.α-MSH: alpha melanocortin stimulating hormone; AgRP: agouti-related peptide; GIP: glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide 1
Table 4
Summary of drugs for management of obesity, with mechanism of action. GLP-1: glucagon-like peptide 1; POMC: pro-opiomelanocortin; GIP: glucose-dependent insulinotropic polypeptide; GCGR: glucagon receptor
| DRUG NAME | PHARMACOLOGIC CLASS |
|---|---|
| Dulaglutide Liraglutide Semaglutide | GLP-1 receptor agonist |
| Tirzepatide | GLP-1 receptor agonist GLP-1 receptor agonist |
| Phentermine | Catecholaminergic |
| Phentermine/Topiramate | Catecholaminergic/GABAergic |
| Bupropion/Naltrexone | POMC stimulation/Opioid antagonist |
| Orlistat | Gastrointestinal lipase inhibitor |
| Setmelanotide | Melanocortin-4 receptor agonist |
| Retatrutide | GLP-1 / GIP / GCGR agonist |
| Orforglipron | Non-peptide oral GLP-1 receptor agonist |
| Cagrilintide | Long-acting amylin receptor agonist |
| Bimagrumab | Activin receptor type 2b monoclonal antibody |