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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.