What are the options for weight loss medication pills, specifically oral medications (e.g. pharmaceuticals) for weight reduction?

From the Guidelines

The most effective weight loss medication pill is Liraglutide (Saxenda), which has been shown to produce significant weight loss when combined with diet and exercise, with a recommended dose of 3.0 mg daily as a subcutaneous injection once daily 1.

Weight Loss Medication Options

Weight loss medications are prescription pills that can help individuals lose weight when combined with diet and exercise. Common FDA-approved options include:

• Orlistat (Xenical, Alli), which blocks fat absorption
• GLP-1 receptor agonists like Liraglutide (Saxenda), which reduce appetite and slow stomach emptying
• Combination medications like Phentermine-topiramate (Qsymia) and Naltrexone-bupropion (Contrave), which affect hunger signals in the brain

Mechanism of Action

These medications typically work by either reducing calorie intake through appetite suppression, blocking fat absorption, or increasing energy expenditure. For example, Liraglutide (Saxenda) mediates weight loss by reducing energy intake by reducing appetite, increasing satiety, and delaying gastric emptying 1.

Recommended Use

To use these medications effectively, individuals should:

• Maintain a calorie-reduced diet
• Exercise regularly
• Have regular follow-ups with their healthcare provider
• Be prescribed by a healthcare provider after a thorough evaluation, typically for individuals with a BMI over 30, or over 27 with weight-related health conditions

Side Effects

Side effects vary by medication but can include gastrointestinal issues, headaches, and increased heart rate. It is essential to discuss potential side effects with a healthcare provider before starting any weight loss medication 1.

From the FDA Drug Label

Table 5: Incidence of Weight Gain or Weight Loss (≥5 lbs) in MDD Trials Using Bupropion HCl Sustained-Release Weight Change Bupropion HCl Sustained- Release 300 mg/day (n=339) Bupropion HCl Sustained- Release 400 mg/day (n=112) Placebo (n=347) Gained >5 lbs 3% 2% 4% Lost >5 lbs 14% 19% 6%

Table 6: Incidence of Weight Gain or Weight Loss (≥5 lbs) in SAD Trials Using Bupropion HCl Extended-Release Weight Change Bupropion HCl Extended-Release 150 to 300 mg/day (n=537) Placebo (n=511) Gained >5 lbs 11% 21% Lost >5 lbs 23% 11%

Weight Loss with bupropion is observed in a significant proportion of patients.

• In MDD trials, 14% to 19% of patients experienced weight loss of ≥5 lbs.
• In SAD trials, 23% of patients experienced weight loss of ≥5 lbs. This suggests that bupropion may be associated with weight loss in some patients 2.

From the Research

Weight Loss Medication Pills

• There are several weight loss medication pills available, including orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, and semaglutide 3, 4, 5, 6.
• These medications have been shown to produce significant weight loss, with semaglutide 2.4 mg weekly producing an average of 15% weight loss at 1 year 3.
• Phentermine-topiramate and liraglutide have been associated with the highest odds of achieving at least 5% weight loss at 52 weeks 4.
• The choice of weight loss medication pill should be guided by individual factors such as contraindications, comorbidities, patient choice, and cost 5.
• Newer medications, such as tirzepatide and cagrilintide/semaglutide combination, are showing promise for even greater weight loss efficacy 3.
• The optimal timing of obesity pharmacotherapy with surgical and endoscopic interventions requires further investigation 6.

Available Medications

• Orlistat: approved for long-term use, produces modest weight loss 4, 5, 6.
• Phentermine/topiramate: approved for long-term use, produces significant weight loss 4, 5, 6.
• Naltrexone/bupropion: approved for long-term use, produces significant weight loss 4, 5, 6.
• Liraglutide: approved for long-term use, produces significant weight loss 4, 5, 6.
• Semaglutide: approved for long-term use, produces significant weight loss 3, 6.

Future Therapies

• Tirzepatide: showing promise for even greater weight loss efficacy 3.
• Cagrilintide/semaglutide combination: showing promise for even greater weight loss efficacy 3.
• Multimodal or multihormonal pharmacotherapy: a promising tool to address challenges such as weight regain and weight loss plateau after surgery 6.