Table 5.
Medications Studied for the Long-Term Treatment of Obesity
| Drug | Status | Common Side Effects | Monitoring and Contraindications | Source |
|---|---|---|---|---|
| Centrally acting anorexigenic agents | ||||
| Phentermine, diethylpropion, and mazindola | Approved only for short-term use in adults | Insomnia, elevation in heart rate, dry mouth, taste alterations, dizziness, tremors, headache, diarrhea, constipation, vomiting, gastrointestinal distress, anxiety, restlessness | Monitor HR, BP. These medications are contraindicated in uncontrolled hypertension, hyperthyroidism, glaucoma, agitated states, history of drug abuse, and MAOIs; use caution when prescribing to patients with even mild hypertension | Rauh and Lipp, 1968 (276); Lorber, 1966 (277); von Spranger, 1965 (278); Andelman et al., 1967 (279); Golebiowska et al., 1981 (280); Komorowski, 1982 (281) |
| Lisdexamfetamine dimesylatea | Not FDA approved for obesity. Approved for binge eating disorder in adults and for attention deficit hyperactivity disorder in patients 6 y of age and older | Dry mouth, sleeplessness (insomnia), increased heart rate, jittery feelings, constipation, anxiety | This medication is contraindicated with MAOIs. There is a risk for sudden death in people who have heart problems or heart defects, and stroke and heart attack in adults. Monitor blood pressure and heart rate. May produce psychotic or manic symptoms, such as hallucinations, delusional thinking, or mania. May worsen peripheral vasculopathy, including Raynaud phenomenon | McElroy et al., 2015 (282); McElroy et al., 2015 (283) |
| Sibutramine | Withdrawn in the US (increased risk of serious cardiovascular events). Still available in some countries such as Brazil | Tachycardia, hypertension, palpitations, insomnia, anxiety, nervousness, depression, diaphoresis | Monitor HR, BP. Do not use with other drugs, MAOIs | Berkowitz et al., 2003 (275); Godoy-Matos et al., 2005 (284); Berkowitz et al., 2006 (285) |
| Lorcaserina | Approved for long-term use in adults | Headache, dizziness, fatigue, nausea, dry mouth, cough, and constipation; back pain, cough, hypoglycemia in patients with T2DM | There is a risk for serotonin syndrome or neuroleptic malignant syndrome-like reactions. Evaluate patients for signs or symptoms of valvular heart disease. Euphoria, hallucination, and dissociation have been seen with supratherapeutic doses. Interactions with triptans, MAOIs, including linezolid, SSRIs, SNRIs, dextromethorphan, tricyclic antidepressants, bupropion, lithium, tramadol, tryptophan, and St. John’s wort | Smith et al., 2010 (286); Fidler et al., 2011 (287) |
| Liraglutidea | Approved for long-term use in adults | Nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase | Monitor heart rate at regular intervals. This medication is contraindicated in patients with a history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2. Discontinue promptly if pancreatitis is suspected | Zinman et al., 2009 (288); Wadden et al., 2013 (289); Astrup et al., 2009 (290) |
| Phentermine plus topiramatea | Approved for long-term use in adults | Paresthesias, dizziness, taste alterations, insomnia, constipation, dry mouth, elevation in heart rate, memory or cognitive changes | This medication is contraindicated in glaucoma, hyperthyroidism, MAOIs. Concerns about teratogenicity (increased risk of oral clefts) mandate effective contraceptive use and pregnancy test monitoring in females. Metabolic acidosis, hypokalemia, and elevated creatinine have been reported, and periodic monitoring is advised. Abrupt withdrawal of topiramate may cause seizures | Garvey et al., 2012 (291); Allison et al., 2011 (292) |
| Bupropion plus naltrexonea | Approved for long-term use in adults | Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, diarrhea | Monitor HR, BP. Do not administer to patients with a history of seizure disorders or with anorexia or bulimia nervosa or to patients who are using opioids or abruptly discontinuing use of alcohol, benzodiazepines, barbiturates, or antiseizure medications. There is potential increased risk of suicidality | Greenway et al., 2010 (293); Padwal, 2009 (294) |
| Drugs in development or used off-label that may act centrally as anorexigenic medications | ||||
| Recombinant human leptin, metreleptina | This drug is under investigation. In monotherapy it was successful for treating leptin deficiency | Headache, abdominal pain | This drug is useful only in leptin deficiency. Antibodies with neutralizing activity have been identified in patients treated with metreleptin. T cell lymphoma has been reported in patients with acquired generalized lipodystrophy. A risk evaluation and mitigation strategy should be in place to prevent inappropriate prescription | Farooqi et al., 2002 (105); Farooqi et al., 1999 (295) |
| Exenatidea | Not FDA approved for obesity | Nausea, vomiting, diarrhea, feeling jittery, dizziness, headache, dyspepsia | Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, has been reported. Observe patients carefully for signs and symptoms of pancreatitis. Discontinue promptly if pancreatitis is suspected. Contraindicated in patients with severe renal impairment | Rosenstock et al., 2010 (296); Kelly et al., 2013 (297); Kelly et al., 2012 (298) |
| Drugs affecting nutrient trafficking | ||||
| Orlistat | This drug is FDA approved for treatment of obesity in adolescents ≥12 y old | Oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, increased defecation, fecal incontinence | This drug is contraindicated in chronic malabsorption syndromes and cholestasis. Cholelithiasis and, rarely, severe liver injury, including hepatocellular necrosis and acute hepatic failure leading to death, have been reported. It decreases drug concentrations of cyclosporine and levothyroxine. Doses should be temporally separated from orlistat. Fat-soluble vitamin absorption is decreased by orlistat. Use with caution in those at risk for renal insufficiency. MVI supplementation is strongly recommended. A low- dose preparation is approved for over-the-counter sale | McDuffie et al., 2002 (299); Zhi et al., 2003 (300); Norgren et al., 2003 (301); Ozkan et al., 2004 (302); McDuffie et al., 2004 (303); Chanoine et al., 2005 (304); Maahs et al., 2006 (305) |
| Drugs affecting internal milieu/metabolic control | ||||
| Metformina | This drug is not FDA approved for obesity. It is approved for ≥10 y of age for T2DM | Nausea, flatulence, bloating, diarrhea; usually resolves | Do not use in renal failure or with i.v. contrast. MVI supplementation is strongly recommended. Potential risk for vitamin B12 deficiency when used long-term. Avoid alcohol intake | Freemark and Bursey, 2001 (306); Atabeck and Pirgon, 2008 (307); Love-Osborne et al., 2008 (308); Wilson et al., 2010 (309); Yanovski et al., 2011 (310); Kendall et al., 2013 (311) |
| Octreotide (for hypothalamic obesity)a | This drug is not FDA approved for obesity | Cholelithiasis (can be prevented by concurrent ursodiol), diarrhea, edema, abdominal cramps, nausea, bloating, reduction in T4 concentrations, decreased GH but normal IGF-I | Monitor fasting glucose, FT4, HbA1c. Useful only for hypothalamic obesity. Ursodiol coadministration is strongly recommended | Gambineri et al., 2005 (312); Haqq et al., 2003 (313); Lustig et al., 2001 (314); Lustig et al., 1999 (315); Lustig et al., 2006 (316) |
| Recombinant human GHa | This drug is not FDA approved for obesity. It is FDA approved in Prader-Willi syndrome to increase height velocity | Edema, carpal tunnel syndrome, death in patients with preexisting obstructive sleep apnea | GH should be used only after screening to rule out obstructive sleep apnea in patients with Prader-Willi syndrome. Clinicians must closely monitor pulmonary function, adrenal function, glucose, HbA1c | Shadid and Jensen, 2003 (317) |
Note: All agents are contraindicated in pregnancy. See full prescribing information for all adverse effects, cautions, and contraindications. Pharmacotherapy is not usually considered if the BMI is below the 95th percentile, but there are additional factors to consider. If we initiate pharmacotherapy early in the course of obesity, we may prevent extreme weight gain and metabolic complications, but we may treat an excess of children and adolescents, raise the rate of unwarranted side effects, and increase the costs to individuals and to society. Alternatively, if we begin medication late in the course of obesity, we run the risk of runaway weight gain and long-term morbidity. One approach that reconciles these difficulties is to act aggressively with lifestyle intervention in overweight and mildly obese patients to prevent extreme obesity and to consider pharmacotherapy when the risk of complications is high or soon after complications emerge. The tipping point for pharmacotherapy could be if the family history is strongly positive for a major comorbidity. Lifestyle intervention should precede pharmacotherapy and should be maintained during pharmacotherapy. Derived from August et al. (86).
Abbreviations: BP, blood pressure; CNS, central nervous system; FT4, (plasma) free thyroxine; HR, heart rate; IV, intravenous; MAOI, monoamine oxidase inhibitor; MVI, multivitamins; SNRI, selective serotonin-norepinephrine reuptake inhibitors; SSRI, selective serotonin-reuptake inhibitors; T4, thyroxine.
a
The use for obesity treatment in children and adolescents <16 y of age of these non–FDA-approved agents should be restricted to large, well-controlled studies.