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GLP-1 / GIP dual agonist

Tirzepatide

Also known as: Mounjaro, Zepbound, LY3298176

Tier 1 — Human RCTReviewed 2026-04-30

FDA-approved dual incretin agonist with the strongest weight-loss and glycemic data in this library.

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Overview

Tirzepatide is a synthetic peptide that activates both the GIP and GLP-1 receptors, slowing gastric emptying, suppressing appetite, and improving insulin sensitivity. It is FDA-approved as Mounjaro for Type 2 diabetes (2022) and as Zepbound for chronic weight management (2023). The SURPASS and SURMOUNT trial programs together enrolled more than 7,000 participants and consistently demonstrated superiority over placebo and over comparator GLP-1 agonists at the clinically relevant endpoints.

Mechanism

Engages GIP and GLP-1 receptors with a long-acting fatty-acid linker that supports once-weekly subcutaneous dosing. The dual mechanism is thought to produce greater appetite suppression and metabolic improvement than GLP-1 monotherapy, though the relative contribution of GIP agonism versus GLP-1 amplification continues to be studied.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Type 2 diabetes

Tier 1high confidence

SURPASS-1 through SURPASS-5 (n>3,000 across the program) demonstrated HbA1c reductions superior to placebo and to semaglutide at matched endpoints. FDA-approved as Mounjaro in May 2022.

Frías JP et al. 2021Eli Lilly and Company et al. 2022

Weight management (obesity / overweight with comorbidity)

Tier 1high confidence

SURMOUNT-1 (n=2,539) showed mean body weight reductions of 15–22% from baseline at 72 weeks, superior to placebo and to comparators. FDA-approved as Zepbound in November 2023.

Jastreboff AM et al. 2022Eli Lilly and Company et al. 2023

Muscle preservation during weight loss

Tier 3high confidence

DEXA substudies of SURMOUNT trials show lean-mass loss in roughly the expected proportion of total weight loss. There is no RCT specifically designed to test muscle preservation in tirzepatide users; claims that tirzepatide preserves muscle better than diet alone are unsupported.

Jastreboff AM et al. 2022

Cardiovascular outcomes

Tier 2medium confidence

SURPASS-CVOT is ongoing. Pooled secondary analyses of SURPASS and SURMOUNT trials suggest favorable cardiometabolic effects, but a dedicated outcomes trial has not yet read out as of this entry's review date.

Frías JP et al. 2021

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

2,500–15,000 mcgonce weekly · subcutaneous

Titration: 2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg, increasing every 4 weeks as tolerated. The 5–15 mg dose range is the studied therapeutic window.

Contraindications

  • Personal or family history of medullary thyroid carcinoma (boxed warning, extrapolated from GLP-1 class data in rodent models)
  • Multiple Endocrine Neoplasia syndrome type 2 (boxed warning)
  • Known hypersensitivity to tirzepatide or excipients
  • Pregnancy: avoid; discontinue 2 months before planned conception
  • Severe gastroparesis or gastrointestinal motility disorders

Reported side effects

  • Nausea (25–30% of users at therapeutic doses; usually peaks during titration)
  • Diarrhea, vomiting, constipation
  • Decreased appetite (intended effect, but can cause undereating)
  • Injection site reactions (mild, transient)
  • Hypoglycemia risk when combined with insulin or sulfonylureas
  • Pancreatitis (rare; discontinue if suspected)
  • Gallbladder disease (cholelithiasis with rapid weight loss)
  • Acute kidney injury, secondary to dehydration from GI side effects

Reconstitution & storage

Distributed as a pre-filled, single-dose KwikPen or single-dose vial. No user reconstitution required for the FDA-approved product. Compounded versions sold for research require sterile reconstitution and stricter handling — the FDA has flagged compounded GLP-1 agonists as a counterfeit risk.

Storage. Refrigerate 2–8 °C. Once removed from refrigeration, can be stored at room temperature (≤30 °C) for up to 21 days. Do not freeze. Discard if shaken vigorously.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

Tirzepatide is the strongest-evidence peptide in this library. The temptation when writing about it is to extrapolate beyond what the trials measured — resist that. Muscle preservation, cognition, and longevity claims are not Tier 1.

Citations

  1. [1]
    Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)
    Frías JP, Davies MJ, Rosenstock J, et al. · New England Journal of Medicine · 2021 · PMID 34170647
    Tier 1 evidence for T2D efficacy vs comparator GLP-1.
    View source
  2. [2]
    Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1)
    Jastreboff AM, Aronne LJ, Ahmad NN, et al. · New England Journal of Medicine · 2022 · PMID 35658024
    Tier 1 evidence for weight loss in obesity; basis for Zepbound approval.
    View source
  3. [3]
    Mounjaro (tirzepatide) Prescribing Information
    Eli Lilly and Company · FDA-approved label · 2022
    Boxed warnings, dose ranges, and contraindications for the T2D indication.
    View source
  4. [4]
    Zepbound (tirzepatide) Prescribing Information
    Eli Lilly and Company · FDA-approved label · 2023
    Boxed warnings and dose ranges for the obesity indication.
    View source