What are the recommended oral medications for weight loss?

From the Guidelines

The most effective oral medications for weight loss are semaglutide (Wegovy, Rybelsus) and tirzepatide (Zepbound, Mounjaro), which are GLP-1 receptor agonists, with patients typically losing 15-20% of their body weight over 68 weeks. These medications are generally prescribed for individuals with a BMI of 30 or higher, or 27 with weight-related health conditions. Other options include orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), and liraglutide (Saxenda) 1.

• Semaglutide and tirzepatide work by reducing appetite and increasing satiety, and are currently considered the most effective options for weight loss.
• Orlistat works by blocking fat absorption in the intestines and is available over-the-counter at lower doses (Alli).
• Phentermine-topiramate combines an appetite suppressant with an anti-seizure medication that also reduces appetite.
• Naltrexone-bupropion combines an addiction medication with an antidepressant to reduce hunger and cravings. These medications work best when combined with lifestyle modifications including diet and exercise, and side effects vary by medication but commonly include nausea, constipation, and diarrhea 1. Most of these medications require a prescription and should be taken under medical supervision, with regular follow-up appointments to monitor progress and side effects.

From the FDA Drug Label

Phentermine Hydrochloride, USP 15 mg and 30 mg is indicated as a short-term (a few weeks) adjunct in a regimen of weight reduction based on exercise, behavioral modification and caloric restriction in the management of exogenous obesity for patients with an initial body mass index greater than or equal to 30 kg/m 2, or greater than or equal to 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). Diethylpropion hydrochloride tablets USP, 25 mg should be used as a short-term adjunct in a regimen of weight reduction based on exercise, behavioral modification, and caloric restriction in the management of exogenous obesity.

The recommended oral medications for weight loss are:

• Phentermine (2): indicated for short-term use in patients with a BMI of 30 kg/m2 or higher, or 27 kg/m2 or higher with other risk factors.
• Diethylpropion (3): used as a short-term adjunct in a regimen of weight reduction based on exercise, behavioral modification, and caloric restriction in the management of exogenous obesity.

Key considerations:

• These medications should be used in conjunction with a weight reduction program that includes exercise, behavioral modification, and caloric restriction.
• Phentermine and diethylpropion are indicated for short-term use only.
• Patients should be carefully evaluated for potential risks, such as pulmonary hypertension and valvular heart disease, before starting treatment with these medications.

From the Research

Oral Weight Loss Options

The following oral medications are recommended for weight loss:

• Orlistat: a lipase inhibitor that blocks the absorption of fat, resulting in an average weight loss of 5% of initial body weight over 16 weeks 4
• Phentermine/topiramate: an anti-obesity medication that has been shown to result in a placebo-subtracted weight reduction of 6.8% 5
• Liraglutide: a medication that has been shown to result in a placebo-subtracted weight reduction of 5.4% 5
• Naltrexone/bupropion: an anti-obesity medication that has been shown to result in a placebo-subtracted weight reduction of 4.0% 5
• Semaglutide: a GLP-1 receptor analog that has been shown to produce an average weight loss of 15% at 1 year 6

Efficacy and Safety

The efficacy and safety of these medications have been studied in various trials:

• Orlistat has been shown to be effective in promoting weight loss and improving cardiovascular risk factor profiles, but is associated with a higher incidence of gastrointestinal adverse events compared to placebo 4, 7
• Liraglutide has been shown to be effective in promoting weight loss, with a greater and more sustained effect compared to orlistat, especially when combined with physical activity 8
• Semaglutide has been shown to produce significant weight loss and improve cardiometabolic outcomes, with a positive outcome in the SELECT trial expected to further promote the concept of weight management as a primary target for cardiometabolic disease control 6

Patient Considerations

When considering treatment with these medications, patient factors such as age, obesity grade, and physical activity level should be taken into account:

• Older adults with grade II or III obesity who perform physical activity and those treated with liraglutide may be more likely to achieve significant weight loss 8
• Patients with defined risk factors at baseline, such as type 2 diabetes, may have smaller effect sizes with orlistat treatment 7