Two incretin therapies, now compared head-to-head. Wegovy (semaglutide) is a GLP-1 receptor agonist; Mounjaro (tirzepatide) is a dual GIP/GLP-1 receptor agonist with greater metabolic efficacy in every head-to-head trial to date. Both are currently private-script only in Australia — see EN-02B for PBS access status.
1Mechanism of action
✓Wegovy (semaglutide) — GLP-1 receptor agonist. Suppresses appetite, delays gastric emptying, and promotes glucose-dependent insulin release. The original incretin therapy for obesity, with the strongest cardiovascular outcome evidence of any weight-loss agent to date (SELECT trial).
✓Mounjaro (tirzepatide) — Dual GIP + GLP-1 receptor agonist (a "twincretin"). GIP co-agonism adds further weight loss and glucose lowering beyond GLP-1 alone, and may attenuate GLP-1-related nausea. Shows superior metabolic efficacy in every head-to-head comparison to date; its own cardiovascular outcomes trial (SURMOUNT-MMO) is still pending.
2Head-to-head efficacy
| Outcome | Wegovy (semaglutide) | Mounjaro (tirzepatide) |
|---|
| Weight loss, 72wks | −13.7% mean body weight (15.0kg) — SURMOUNT-5 | −20.2% mean body weight (22.8kg) — SURMOUNT-5 |
| 25%+ weight loss | 16.1% of patients — SURMOUNT-5 | 31.6% of patients — SURMOUNT-5 |
| HbA1c reduction (T2DM) | −1.86% at 1mg — SURPASS-2 | −2.09 to −2.46% at 5–15mg — SURPASS-2 |
| CV outcomes (MACE) | 20% MACE reduction vs placebo — SELECT trial | Outcomes trial (SURMOUNT-MMO) still pending vs placebo |
3Dose escalation
Wegovy — dose escalation
- Weeks 1–4: 0.25mg weekly.
- Weeks 5–8: 0.5mg weekly.
- Weeks 9–12: 1.0mg weekly.
- Weeks 13–16: 1.7mg weekly.
- From week 17: 2.4mg maintenance — takes 16 weeks to reach target; don't accelerate escalation, it increases GI side effects.
Mounjaro — dose escalation
- Weeks 1–4: 2.5mg weekly (titration only).
- Then escalate by 2.5mg every ≥4 weeks: 5mg → 7.5mg → 10mg → 12.5mg → 15mg maximum.
- Maintenance doses are 5mg, 10mg or 15mg; many patients are maintained at 5–10mg.
- Takes up to 20 weeks to reach the maximum dose. If on insulin or a sulfonylurea, reduce that dose by 20–50% when starting, to avoid hypoglycaemia.
Safety
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 — absolute contraindication (boxed warning) for both agents.
- Active pancreatitis — discontinue if suspected; use caution if there's a prior history.
- Both agents are contraindicated in pregnancy and are not indicated for Type 1 diabetes.
Check / exclude
- Confirm the patient isn't already on another GLP-1RA or dual GIP/GLP-1 agonist — never combine two incretin therapies.
- Confirm no personal or family history of MTC/MEN2; counsel to report a neck mass, dysphagia or hoarseness.
- Confirm effective contraception in those of childbearing potential before starting.
EN-02A v1.0 · Reviewed Jun 2026 · Review Dec 2026
For health-professional use. Evidence: SURMOUNT-5 (NEJM 2025); SELECT (NEJM 2023); SURPASS-2 (NEJM 2021). Companion sheet: EN-02B Wegovy & Mounjaro — PBS Access & Patient Selection.
