1. Traditional approaches (diet, exercise, behavioral programs)
- Average weight loss: About 5–10% of body weight after 6–12 months, if the program is intensive and well supported.
- Challenges:
- Weight loss often plateaus after the first months.
- Long-term maintenance is difficult; many regain weight within 2–5 years.
- Requires sustained lifestyle change, which can be difficult without ongoing support.
- Benefits:
- Improves health markers (blood pressure, cholesterol, blood sugar).
- No medication side effects.
- Limitations: For people with obesity (BMI ≥30, or ≥27 with comorbidities), lifestyle changes alone often do not achieve clinically significant, durable weight loss.
2. Wegovy (semaglutide 2.4 mg)
- Average weight loss:
- STEP-1 trial: −14.9% at 68 weeks (vs −2.4% placebo).
- Long-term: Maintained ~15% over 2 years.
- Comparison to lifestyle programs: About 1.5–3 times greater weight loss than intensive behavioral interventions.
- Durability: Weight loss can be sustained for years if the medication is continued; stopping often leads to regain.
- Extra benefit: 20% lower risk of heart attack/stroke in people with CVD (SELECT trial).
3. Mounjaro (tirzepatide)
- Average weight loss:
- SURMOUNT-1 trial: 15–21% at 72 weeks (dose dependent).
- Head-to-head trial (SURMOUNT-5): Tirzepatide produced ~50% more weight loss than semaglutide (−20.2% vs −13.7%).
- Comparison to lifestyle programs: About 2–4 times greater weight loss than diet + exercise alone.
- Durability: Sustained while on treatment; similar to Wegovy, discontinuation usually leads to regain.
- Extra benefit: Pending cardiovascular outcome data (not yet confirmed as with semaglutide).
4. Traditional weight-loss medications (older options)
- Orlistat: Typically 3–5% more weight loss than diet alone; limited by GI side effects.
- Phentermine/topiramate (not widely available in EU): 8–10% average weight loss, but with potential CNS/cardiovascular side effects.
- Compared to new GLP-1/GIP drugs: Effect size is smaller and less durable.
5. Side-by-side effectiveness snapshot
| Approach | Average weight loss | Long-term maintenance | Key notes |
| Lifestyle only (diet + exercise + behavior) | 5–10% | Often partial regain within 2–5 years | No drug risks |
| Older drugs (e.g., orlistat) | 3–10% | Variable, modest durability | Limited by tolerability |
| Wegovy (semaglutide 2.4 mg) | ~15% | Maintained ≥2 years with continued use | CV protection proven |
| Mounjaro (tirzepatide) | 15–21% | Maintained ≥1.5 years with continued use | Greatest weight loss, CV benefit pending |
6. Key takeaways
- New GLP-1/GIP medications achieve roughly double to quadruple the weight loss of traditional lifestyle or older pharmacological approaches.
- Tirzepatide (Mounjaro) is currently the most effective, producing average 20% reductions in body weight.
- Semaglutide (Wegovy) is slightly less potent but has proven cardiovascular benefit in patients with heart disease.
- Lifestyle changes remain essential for overall health and help maximize and maintain results from medication.
⚠️Important note: These numbers reflect averages in large clinical trials. Individual results vary. Medication use must always be guided by a healthcare professional.
