Quick study on the 5 FDA approved obesity drugs
A recent study found that patients went to the pharmacy 15 times more frequently for antidiabetic drugs than for antiobesity medications even though 116 million adults fit the criteria for use of these drugs, compared with less than 30 million for whom antidiabetes drugs are indicated.
Why? Why are we so reluctant to prescribe these drugs? Experts cite a number of reasons. One is a belief that obesity does not require pharmacotherapy, although the experience of virtually every clinician would argue that many, if not most, patients cannot achieve meaningful weight loss with behavioral changes alone. Others point to concerns about insurance coverage for these agents, which may not be approved by an individual patient’s insurance plan and can cost about $200 per month—a price that many frustrated patients may well be willing to pay. Perhaps most important, primary care clinicians are just not familiar with these agents, nor comfortable with prescribing them.
Available agents are able to help patients achieve, on average, 5%-15% weight loss, which usually leads to significant improvements in many comorbid conditions, including hyperglycemia and diabetes, hyperlipidemia, hypertension, and others.
What do you need to know? The US Food and Drug Administration (FDA) has approved five medicines for long term use, including four relatively new drugs—the first drugs approved for obesity in 13 years—with solid data on long-term efficacy and safety. The indications for all are either a body mass index (BMI) > 30 kg/m² or a BMI > 27 kg/m² with comorbidity.
Here, we provide a brief primer describing the five medications that are approved for long-term use for obesity management. To view the table, click here. For a downloadable table that can be printed and shared, click here.
Type of drug/actions: Peripherally acting pancreatic lipase inhibitor; reduces absorption of ingested fat.
Effects: Orlistat plus behavioral counseling doubled weight loss seen with placebo/counseling. Progression to diabetes reduced.
Dosing: 120 mg three times daily with meals (or over-the-counter alli® at half dose, 60 mg)
Adverse effects: Gastrointestinal (diarrhea, flatulence), especially if large amounts fat are ingested.
Precautions: Binds fat-soluble vitamins. Patient should take a multivitamin at bedtime. Follow a reduced-fat, reduced-calorie diet.
Contraindications: Pregnancy, cholestasis, chronic malabsorption syndromes, coadministration with cyclosporine. Can increase urinary oxalate and predispose to kidney stones.
Type of drug/actions: Combination of appetite-suppressant sympathomimetic amine and anticonvulsant.
Effects: Additive effect of drug combination leads to more weight loss than either agent alone; reduced progression to type 2 diabetes.
Dosing: 3.75 mg phentermine/23 mg topiramate ER; escalate to 7.5/46 mg after 2 weeks. Response should be evaluated after 12 weeks, and treatment should either be escalated to a higher dose or discontinued if patients do not achieve ≥ 3% weight loss.
Adverse effects: Paresthesia, dizziness, dysgeusia, insomnia, constipation, dry mouth.
Precautions: Pregnancy, glaucoma, use of monoamine oxidase inhibitors (MAOIs), hyperthyroidism.
Contraindications: Topiramate is a known teratogen; pregnancy should be ruled out before starting the medication, and women of childbearing age should use contraception and have monthly pregnancy testing during use.
Type of drug/actions: Selective serotonin 2c (5HT-2c) receptor agonist; stimulates 5HT-2c receptors (not other serotonin receptors) in the appetite center of the brain.
Effects: Average weight loss 8%; improved blood pressure, lipids, glycemic control.
Dosing: 10 mg twice daily; does not require titration. Discontinue if the patient does not lose 5% of weight after 12 weeks.
Adverse effects: Headache, dizziness, fatigue, nausea, dry mouth, constipation; hypoglycemia with concomitant antidiabetic agents.
Precautions: Risk for serotonergic syndrome/neuroleptic malignant syndrome if the patient is taking serotonergic or antidopaminergic agent. Caution in patients with valvular heart disease, congestive heart failure, psychiatric disorders; priapism risk.
Type of drug/actions: Bupropion (a dopamine and norepinephrine reuptake inhibitor used to treat depression and smoking cessation) and naltrexone (an opioid receptor antagonist used to treat addiction). Effects may occur in the hypothalamic appetite center or the mesocorticolimbic dopamine system and other brain areas related to reward-driven behaviors.
Actions: Long-term use; combination produces > 8% weight loss (diminished appetite and cravings); > 12% weight loss when combined with intensive lifestyle intervention. Also improves glycemic control.
Dosing: Week 1: one pill (8 mg naltrexone/90 mg bupropion) daily; escalate weekly to target dose of two pills twice daily (total, 32/360 mg) by week 4. Evaluate response after 12 weeks on target dose; stop treatment if weight loss < 5%.
Adverse effects: Nausea, constipation, diarrhea, headache; most resolve in days to weeks and do not recur.
Precautions: Warning about suicidal thoughts in patients < 24 years.
Contraindications: Uncontrolled hypertension; seizure disorders; chronic opioid use; MAOI use; pregnancy.
Other considerations: May be a good choice for patients with comorbid depression, as well as those who wish to quit smoking.
Type of drug/actions: Glucagon-like peptide 1 receptor agonist.
Effects: Achieved 9% weight loss; 71% maintained at 3 years. Reduced progression to diabetes by 80%.
Dosing: Requires daily subcutaneous injection (abdomen, arm, or thigh; rotate injection site). Start with 0.6 mg; titrate by 0.6 mg/week for 5 weeks to target dose of 3.0 mg. Evaluate response after 16 weeks; stop treatment if weight loss < 4%.
Adverse effects: Nausea; gastrointestinal symptoms.
Precautions: Hypoglycemia can occur in patients on antidiabetic medications; may be severe in patients concomitantly treated with sulfonylureas or insulin.
Contraindications: History of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, acute pancreatitis, pregnancy, breastfeeding.
Other considerations: May be a good choicer for patients with or at risk for diabetes or prediabetes and those unlikely to become pregnant.
An expanded discussion of the clinical trial findings and case studies in pharmacologic obesity management can be found in Using Anti-obesity Drugs: Which Drug for Which Patient?