A New Era in Weight Loss Medications – From Single Gut Hormones to Multi-Receptor Precision Therapy
Update Date：2026/02/06，
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Endocrinology and Metabolism Department, Dr. Li Ming-Rui
Over the past decades, obesity was often misunderstood as a result of “lack of willpower,” but recent medical research has clearly demonstrated that obesity is a chronic, relapsing metabolic disease closely linked to Type 2 diabetes, cardiovascular diseases, fatty liver, sleep apnea, and degenerative joint diseases. For most patients, relying solely on diet control and exercise is difficult to maintain in the long term, making medication therapy a crucial component of treatment.
1. GLP-1 Agonists: The Cornerstone of Weight Loss Therapy
The major breakthrough in weight loss medications began with the introduction of GLP-1 (glucagon-like peptide-1) receptor agonists. Initially used for the treatment of diabetes, these medications were later found to suppress appetite through the central nervous system, delay gastric emptying, and promote satiety, all while posing a minimal risk of hypoglycemia.
Semaglutide, a once-weekly GLP-1 medication (e.g., Wegovy®), can help patients lose an average of about 15% of their body weight within a year. It also improves blood glucose, lipids, and reduces cardiovascular and kidney risks, marking a significant change in the standard for obesity treatment.
However, obesity is not solely caused by a single hormonal imbalance, prompting researchers to explore whether simultaneously regulating multiple gut and pancreatic hormone pathways could yield even better results.
2. Dual and Triple Agonists: Breaking Through a 20% Weight Loss Threshold
The new generation of weight loss drugs is based on the concept of multi-receptor agonism.
(1).GLP-1 / GIP Dual Agonists (e.g., Tirzepatide: Mounjaro®): GIP (gastric inhibitory peptide) is another gut hormone that plays a role in fat metabolism and energy utilization. Tirzepatide stimulates both GLP-1 and GIP receptors, and in large clinical trials, non-diabetic obese patients lost an average of around 20% of their body weight, significantly outperforming traditional GLP-1 medications.
(2).GLP-1 / Glucagon Dual Agonists (e.g., Survodutide, Mazdutide): Glucagon, previously thought to raise blood sugar, can, at certain doses, increase energy expenditure and promote fat burning. When combined with GLP-1, this dual effect helps suppress appetite and increase metabolic rate, particularly beneficial for obesity and fatty liver.
(3).GLP-1 / GIP / Glucagon Triple Agonists (e.g., Retatrutide): These drugs are considered the "ceiling" of weight loss medications. Clinical trials show that some patients can lose over 25% of their body weight in a year, nearly mimicking the effects of metabolic surgery.
3. Amylin and GLP-1 Combo: A New Strategy for Enhanced Satiety
In addition to gut hormones, Amylin (a hormone produced by the pancreas) is an important regulator of appetite. Amylin suppresses food intake, delays gastric emptying, and does not significantly reduce basal metabolic rate.
The new-generation drug CagriSema (cagrilintide + semaglutide) combines the mechanisms of Amylin and GLP-1, showing weight loss of over 22% in research studies, with even more stable results.
4. The Rise of Oral Weight Loss Medications: The Possibility of Saying Goodbye to Injections
Previously, most GLP-1 medications required injections, but recent developments have successfully created oral alternatives:
•High-dose oral semaglutide
•Small-molecule oral GLP-1 agonists (e.g., Orforglipron)
These drugs are resistant to stomach acid and are absorbed consistently, with clinical trials showing a weight loss of 10-15%. If safety is confirmed, these treatments will significantly improve patient acceptance and the feasibility of long-term therapy.
5. Safety and Muscle Loss: Critical Considerations
Although new weight loss medications are highly effective, certain side effects should not be overlooked:
•Gastrointestinal side effects (nausea, vomiting, diarrhea) are common but can usually be improved by slow dosage escalation.
•Patients with a history of medullary thyroid cancer or Type 2 Multiple Endocrine Neoplasia Syndrome should not use GLP-1 medications.
•Muscle loss (sarcopenia): Rapid weight loss may result in muscle loss, so it’s recommended to ensure sufficient protein intake, resistance training, and possibly combine treatment with "muscle-preserving" drugs in the future.
6. Conclusion: Weight Loss Treatment Moving Toward Precision Medicine
From single GLP-1 medications to dual and triple receptor agonists, and now oral small-molecule drugs, weight loss therapy is quickly evolving into a highly efficient, long-term, and personalized new generation.
The goal of future treatments is not just weight loss but also to reduce the risk of diabetes, cardiovascular diseases, kidney disease, and fatty liver, ultimately improving overall health and quality of life.
Although most multi-receptor agonists are still in clinical trials, their preliminary results are promising. Once available, these medications will play a key role in weight loss and health promotion.
If you are considering weight loss medication, it is advised to have a thorough discussion with an endocrinologist to choose the most appropriate and safe treatment strategy based on your individual health status and risk evaluation.