GLP-1 Family Compared: Semaglutide, Tirzepatide, Retatrutide, Mazdutide
May 9, 2026 · Education
“GLP-1” has become shorthand for any injectable weight-loss drug, but the class is actually a spectrum — from single-receptor agonists to triple-receptor compounds. Knowing what each one targets explains why some work better than others, why side effects differ, and which fits which person.
The receptors involved
- GLP-1 receptor — activated by glucagon-like peptide 1. Slows gastric emptying, increases satiety, improves insulin sensitivity.
- GIP receptor — activated by glucose-dependent insulinotropic polypeptide. Adds insulin response and may improve fat handling.
- Glucagon receptor — counterintuitively, partial activation increases energy expenditure (your metabolic rate goes up).
The newer compounds activate more receptors simultaneously. More receptors = more weight loss, but typically more side effects too.
Semaglutide (single agonist: GLP-1)
- Brand names: Ozempic, Wegovy, Rybelsus (oral)
- Trial weight loss: ~15% body weight at high dose
- Dosing: 0.25 mg → 2.4 mg weekly subQ over 16+ weeks
- Strengths: Most-studied. Strong cardiovascular outcome data. Available in oral form.
- Weaknesses: Less effective than dual/triple agonists. Common nausea.
Tirzepatide (dual agonist: GLP-1 + GIP)
- Brand names: Mounjaro, Zepbound
- Trial weight loss: ~15-22% body weight at high dose
- Dosing: 2.5 mg → 15 mg weekly subQ over 20+ weeks
- Strengths: Significantly better weight loss than semaglutide. Often better tolerated than equivalent-dose sema.
- Weaknesses: GI side effects scale with dose. Constipation common.
Retatrutide (triple agonist: GLP-1 + GIP + Glucagon)
- Status: Phase 3 trials ongoing
- Trial weight loss: ~24% at high dose at 48 weeks
- Dosing: 2 mg → 12 mg weekly subQ over 20+ weeks
- Strengths: Most effective compound in late-stage trials. Glucagon component raises metabolic rate.
- Weaknesses: Strongest GI side effect profile. Increased heart rate reported. Slow titration essential.
Mazdutide (dual agonist: GLP-1 + Glucagon)
- Status: Approved in China, Phase 3 elsewhere
- Trial weight loss: ~14-15% at high dose
- Dosing: 3 mg → 9 mg weekly subQ
- Strengths: Different receptor combination than tirzepatide — may work for non-responders. Claimed liver-fat reduction.
- Weaknesses: Less Western trial data. Available primarily through Chinese pharma channels.
How to choose
| Profile | Best fit | Why |
|---|---|---|
| BMI 27-32, first GLP-1 | Semaglutide or Tirzepatide | Most established. Insurance often covers semaglutide. |
| BMI 33+, plateaued on sema | Tirzepatide or Retatrutide | Stronger effect; tirzepatide more tolerable. |
| BMI 35+, large weight to lose | Retatrutide | Highest weight-loss potential. Slow titration. |
| Liver / metabolic disease focus | Mazdutide or Retatrutide | Glucagon component improves liver fat. |
| Oral preference | Semaglutide (Rybelsus) | Only oral option in class. |
What they all share
- Slow titration is non-negotiable. Most side effects come from going up too fast.
- Pancreatitis, gallstones, and (theoretical) thyroid concerns apply across class.
- Tapering at the end of cycle reduces rebound hunger.
- Resistance training during use preserves lean mass.
Reference information only. Not medical advice. Bloodwork and provider oversight strongly recommended.