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Tirzepatide

Mounjaro · Zepbound

A dual incretin agonist that has produced the largest weight reductions yet seen in obesity pharmacotherapy trials.

How it works

Activates both GIP and GLP-1 receptors. The added GIP activity appears to improve insulin sensitivity and lipid handling while blunting some of the nausea associated with pure GLP-1 agonism.

Structure: 39 amino acid dual GIP/GLP-1 agonist

Reported benefits

  • Up to ~21% mean weight loss at 15 mg in SURMOUNT-1
  • Superior HbA1c reduction versus semaglutide in head-to-head trials
  • Improvements in sleep apnoea and blood pressure

Practical considerations

  • Same muscle-preservation caveats as semaglutide
  • Slow titration is essential
  • High cost and periodic supply constraints

Side effects and risks

  • Nausea
  • Decreased appetite to the point of undereating
  • Diarrhoea
  • Rare pancreatitis

Dosing overview

2.5 mg weekly starting dose, escalating in 2.5 mg steps up to 15 mg

This describes doses reported in published literature and community protocols. It is not a recommendation, and it is not a substitute for clinical supervision.

Research references

  • Jastreboff et al., 2022 — SURMOUNT-1, NEJM