From the Guidelines
The newest medications for weight loss include semaglutide 2.4 mg, liraglutide 3.0 mg, phentermine-topiramate ER, and naltrexone-bupropion ER, which have been shown to have a moderate or large magnitude of weight loss and small or not-substantial harms. These medications work by mimicking the hormone GLP-1, activating the sympathetic nervous system, or altering appetite and energy intake. Semaglutide is typically started at 0.25mg weekly, gradually increasing to 2.4mg weekly for weight management, as noted in the 2022 study 1. The mechanisms of action for these medications include:
- Semaglutide: mimicking the hormone GLP-1, which regulates appetite and food intake by increasing feelings of fullness, slowing stomach emptying, and affecting brain centers that control hunger
- Liraglutide: reducing energy intake by reducing appetite, increasing satiety, and delaying gastric emptying
- Phentermine-topiramate ER: reducing appetite and affecting food intake via the enhancement of norepinephrine release and blockade of norepinephrine reuptake, as well as altering appetite and decreasing energy intake
- Naltrexone-bupropion ER: activating POMC neurons in the arcuate nucleus, causing release of alpha-melanocyte–stimulating hormone, which projects to other hypothalamic areas involved in feeding and body weight control. These medications are administered as subcutaneous injections or oral tablets and are generally prescribed for long-term use in individuals with BMI ≥30 or BMI ≥27 with weight-related conditions, as recommended in the 2022 study 1. Common side effects include nausea, vomiting, and diarrhea, which often improve over time. These medications are effective because they address the biological drivers of hunger and metabolism rather than simply restricting calories, leading to sustainable weight loss of 15-20% of body weight for many patients when combined with lifestyle modifications, as noted in the 2023 study 1. They also offer additional benefits like improved blood sugar control and cardiovascular outcomes in many patients.
Some key points to consider when prescribing these medications include:
- Semaglutide and liraglutide are GLP-1 receptor agonists that have been shown to be effective for weight loss and improving glycemic control
- Phentermine-topiramate ER is a combination medication that has been shown to be effective for weight loss and may be considered in patients with obesity and migraine headaches
- Naltrexone-bupropion ER is a combination medication that has been shown to be effective for weight loss and may be considered in patients with obesity and a history of substance abuse. It is essential to individualize treatment goals and consider the cost of these medications, as well as potential side effects and interactions, when making prescribing decisions, as noted in the 2022 study 1.
From the Research
Newest Medications for Weight Loss
The newest medications for weight loss include semaglutide, tirzepatide, and setmelanotide. These medications have shown promise in clinical trials for their efficacy in weight loss and management of obesity-related comorbidities.
Mechanism of Action
- Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that works by enhancing glycemic control and promoting weight loss 2, 3, 4.
- Tirzepatide is a dual GIP and GLP-1 receptor agonist that has shown greater weight loss efficacy in phase 3 clinical trials 2.
- Setmelanotide is a melanocortin 4 receptor agonist that is approved for the treatment of severe, early-onset obesity due to certain genetic diseases 2.
Efficacy and Safety
- Semaglutide has demonstrated an average weight loss of 15% at 1 year, accompanied by improvements in cardiovascular risk factors and physical functioning 3, 4.
- Tirzepatide has shown promise for even greater weight loss efficacy in phase 3 clinical trials 2.
- Setmelanotide has been shown to be effective in reducing body weight in patients with severe, early-onset obesity due to certain genetic diseases 2.
Real-World Effectiveness
- A real-world study of semaglutide treatment in patients with obesity or overweight and diabetes found that it induced weight loss maintenance after 12 and 24 months of treatment, with significant reductions in body weight and improvements in glycometabolic control 5.
FDA-Approved Medications
- The FDA has approved seven anti-obesity medications, including phentermine, orlistat, phentermine/topiramate ER, naltrexone SR/bupropion SR, liraglutide 3.0 mg, semaglutide 2.4 mg, and tirzepatide 6.