Curriculum
Module 04 · 55 min

Tirzepatide & Multi-Agonists

Dual GIP/GLP-1, GLP-1/glucagon, and triple agonists — beyond Ozempic.

CoreClinicalAdvanced
Core topics

What's covered

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Learning objectives

By the end of this module you will be able to

  • L01Compare tirzepatide and semaglutide on efficacy, GI burden, and trial outcomes.
  • L02Describe the rationale for adding GIP and glucagon receptor activity.
Expected takeaways

What you should walk away believing

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Lesson · Core emphasis

What this means for you

Patient summary

Tirzepatide (Mounjaro / Zepbound) hits two gut-hormone receptors instead of one, and tends to produce more weight loss than semaglutide for most patients.

Clinician summary

SURMOUNT-1 mean weight loss at 72 wk: placebo −3.1%, tirzepatide 5 mg −15.0%, 10 mg −19.5%, 15 mg −20.9%. CV outcome trial (SURPASS-CVOT) read-out anticipated.

Advanced note

Retatrutide phase II showed mean −24.2% at 48 wk (Jastreboff NEJM 2023) — extrapolating long-term safety remains the open question.

Evidence-graded claims

What the data say

A
Tirzepatide outperforms semaglutide on weight loss head-to-head (SURMOUNT-5)
Tirzepatide −20.2% vs semaglutide −13.7% at 72 wk.
C
Triple agonists (retatrutide) will have a comparable safety profile to GLP-1 RAs at scale
Glucagon-arm hepatic and energy-expenditure effects need long-term observation.
Quick check

Test yourself

Q1Tirzepatide receptor targets?
Q2Approved obesity brand name for tirzepatide?
Flashcards · Spaced repetition

Lock it in — review what's due

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SURMOUNT-1 headline?
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References · 6

Sources cited in this module

  1. [1]
    Standards of Care in Diabetes — 2025
    American Diabetes Association · 2025Guideline · T1
  2. [2]
    Tirzepatide for HFpEF and Obesity (SUMMIT)
    Packer M. et al. · NEJM · 2024RCT · T1
  3. [3]
    Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
    Jastreboff AM. et al. · NEJM · 2022RCT · T1
  4. [4]
    Tirzepatide vs Semaglutide in T2D (SURPASS-2)
    Frías JP. et al. · NEJM · 2021RCT · T1
  5. [5]
    Survodutide for MASH — Phase 2
    Sanyal AJ. et al. · NEJM · 2024RCT · T2
  6. [6]
    Triple-Hormone-Receptor Agonist Retatrutide for Obesity — Phase 2
    Jastreboff AM. et al. · NEJM · 2023RCT · T2
Browse full references library →
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GLP-1 Receptor Agonists
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BPC-157, TB-500 & 'Healing Peptides'