Free Guide
GLP-1 Medication Comparison Guide
Understanding your medication is the first step to maximizing its effectiveness. Here's what the science says about the three major GLP drug classes — and what it means for your diet and training.
This is educational content only. Always consult your prescribing physician about medication-specific questions, dose titration, and side effect management.
| Feature | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Mechanism | GLP-1 agonist | GIP + GLP-1 dual agonist | Triple agonist (GLP-1 + GIP + Glucagon) |
| Avg. Weight Loss | ~15% | ~20–22% | ~24% (Phase 2) |
| FDA Status | Approved | Approved | Phase 3 Trials |
| Main Side Effects | Nausea, GI (moderate) | GI distress (dose-dependent) | GI distress (most common) |
| Muscle Loss Risk | Moderate (without resistance training) | Higher (greater weight loss) | Potentially Higher (glucagon) |
Semaglutide
Ozempic · Wegovy · Rybelsus
How It Works
Mimics the natural GLP-1 hormone released after eating. Signals the pancreas to release insulin in response to blood sugar, slows gastric emptying, and reduces appetite via the brain's satiety centers.
Weight Loss Potential
~15% average body weight loss
Common Side Effects
- Nausea (most common, peaks during titration)
- Diarrhea or constipation
- Vomiting
- Fatigue during dose increases
Diet Strategy
High protein is critical — semaglutide's strong appetite suppression makes it easy to under-eat protein. Target 1.0–1.2g per lb of goal body weight.
Training Strategy
Resistance training is essential on semaglutide. Studies show 25–40% of weight lost on GLP-1s without resistance training is muscle mass.
Tirzepatide
Mounjaro · Zepbound
How It Works
Activates both the GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. The dual mechanism delivers superior glucose control and greater weight loss than GLP-1 alone. GIP may also improve fat metabolism and reduce GLP-1 side effects.
Weight Loss Potential
~20–22% average body weight loss (SURMOUNT trials)
Common Side Effects
- GI distress (dose-dependent)
- Nausea, diarrhea — generally comparable to semaglutide
- Injection site reactions
Diet Strategy
With greater weight loss potential comes greater muscle loss risk. Tirzepatide users should emphasize protein above all macros and consider creatine supplementation.
Training Strategy
Progressive overload with compound movements (squats, deadlifts, presses) is the best defense against muscle loss. The MAXX program is ideal.
Retatrutide
Investigational (Phase 3 trials)
How It Works
The most advanced class currently in trials. Adds glucagon receptor activation to the GIP/GLP-1 dual mechanism. Glucagon receptor targeting increases resting energy expenditure and drives additional fat mobilization from adipose tissue.
Weight Loss Potential
~24% at highest doses (Phase 2 data — most of any drug in class)
Common Side Effects
- GI distress (most common, peaks at titration)
- Nausea, diarrhea
- Potential for greater muscle mass impact (glucagon catabolic effect being studied)
Diet Strategy
If Retatrutide becomes available, protein targets may need to increase to 1.2–1.4g/lb of goal weight due to glucagon's potential catabolic effects.
Training Strategy
Training intensity matters more than volume. Prioritize heavy compound lifts to send a strong anabolic signal while in a deep caloric deficit.
Now That You Know Your Medication…
Get the specialized diet and training program designed for your specific GLP medication.