1. Why weight loss is hard: the body’s hormonal defense system
When you lose weight, the body interprets it as a threat to survival and activates compensatory hormones to restore lost weight. Key players include:
- Leptin (from fat tissue): Normally signals “I’m full.” With weight loss, leptin levels drop → hunger increases.
- Ghrelin (from the stomach): “Hunger hormone.” Levels rise after weight loss → stimulates appetite.
- Insulin (from the pancreas): Lower body fat can improve insulin sensitivity, but in people with insulin resistance, the body may still “defend” fat stores.
- Peptide YY & GLP-1 (from the gut): Satiety hormones that decrease with dieting → less sense of fullness.
- Cortisol & stress hormones: Can promote fat storage, especially around the abdomen.
Result: After dieting, hunger increases, metabolism slows, and the body becomes more efficient at storing calories — making long-term weight maintenance difficult.
2. How Wegovy and Mounjaro help reset the balance
Wegovy (semaglutide, GLP-1 receptor agonist)
- Mimics GLP-1, a natural gut hormone.
- Effects:
- Increases satiety signals in the brain → less hunger.
- Slows gastric emptying → food stays longer in the stomach, increasing fullness.
- Reduces “reward-driven eating” by acting on brain reward pathways.
- Counteracts: The drop in GLP-1 and PYY after weight loss, and the rise in ghrelin.
Mounjaro (tirzepatide, dual GIP + GLP-1 receptor agonist)
- Activates both GLP-1 and GIP receptors.
- Effects:
- Same satiety and appetite suppression as semaglutide.
- Additional benefit from GIP: may improve fat metabolism and further enhance weight loss.
- Counteracts: Multiple hormonal adaptations, producing greater average weight loss than GLP-1 alone.
3. Why these drugs are different from dieting alone
- Dieting lowers satiety hormones and raises hunger hormones → strong drive to regain weight.
- GLP-1/GIP medications replace or enhance missing satiety signals, making the brain believe the body is well-fed.
- This helps patients not only lose more weight but also maintain weight loss, something traditional diets rarely achieve long-term.
4. Beyond appetite: metabolic and hormonal benefits
- Insulin sensitivity: Both drugs improve insulin action, lowering blood sugar and reducing fat storage signals.
- Glucose control: Originally developed for diabetes, they help regulate post-meal blood sugar spikes.
- Energy balance: By modulating hormones, they shift the “set point” the body defends, allowing a lower weight to feel “normal.”
5. Key takeaway
- Hormonal adaptation is the main reason diets often fail long-term.
- Wegovy and Mounjaro work by restoring satiety signals and reducing hunger hormones, helping overcome the body’s natural resistance to weight loss.
- Mounjaro (tirzepatide) generally produces greater effect because it targets two hormones (GLP-1 + GIP), while Wegovy (semaglutide) targets GLP-1 only.
⚠️ Note: While these medications address powerful biological barriers to weight loss, they work best when combined with lifestyle changes (nutrition, activity, stress management). They are medical treatments and must be prescribed and monitored by a healthcare professional.
