Educational reference only. Nothing on this page constitutes medical advice or encourages personal use of this compound. Always consult a qualified healthcare provider before any decision involving your health.

Tirzepatide

Mounjaro · Zepbound · LY3298176 · Tirz

Strong human RCT

FDA-approvedGLP-1/GIP Dual Agonist Incretin Mimetic

RouteInjectableFDA-approved

Evidence grade: Strong human RCT

Multiple high-quality randomized controlled trials in humans. Grades summarize evidence quality, not whether a compound is appropriate, legal, or risk-free.

At a glance

What it is: Tirzepatide (LY3298176) — GLP-1/GIP Dual Agonist, Incretin Mimetic.
Why people use it: Used primarily for weight loss.
What the evidence supports: SURMOUNT-4 (JAMA 2023) and the post-hoc JAMA Internal Medicine analysis (February 2026) together provide the most current and comprehensive tirzepatide withdrawal data. The core finding: among participants who had achieved ≥10% weight reduction on 36 weeks of tirzepatide and then stopped, the mean weight regain was 14% over the subsequent 52 weeks. More importantly, the JAMA Int Med post-hoc analysis showed that >25% of initial weight loss was regained in most patients within 1 year — and those who regained the most weight had the greatest reversal of cardiometabolic benefits (HbA1c rose, blood pressure increased, lipids worsened proportionally to weight regained). The editorial accompanying the post-hoc analysis made the clinical point explicitly: 'There is a common misconception that patients can stop antiobesity medications when they reach their goal weight and maintain the weight that they lost and the cardiometabolic benefits they achieved.' The data contradicts this misconception directly.
Key risks: Key risks: Personal or family history of MTC or MEN-2.

If you only read one thing

Best-in-class weight loss with the strongest evidence base on this site; tolerability and cost are the practical limits.

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Published literature

12human RCTs8human studies35animal20in vitro

Among the most thoroughly trialed compounds on this site — 25,000+ patients across the SURPASS and SURMOUNT programs.

Evidence reality check

Human evidence

20 human studies

12 randomized; 8 observational.

Preclinical base

55 lab signals

35 animal; 20 in-vitro/mechanistic.

Evidence snapshot

SURMOUNT-4 (JAMA 2023) and the post-hoc JAMA Internal Medicine analysis (February 2026) together provide the most current and comprehensive tirzepatide withdrawal data. The core finding: among participants who had achieved ≥10% weight reduction on 36 weeks of tirzepatide and then stopped, the mean weight regain was 14% over the subsequent 52 weeks. More importantly, the JAMA Int Med post-hoc analysis showed that >25% of initial weight loss was regained in most patients within 1 year — and those who regained the most weight had the greatest reversal of cardiometabolic benefits (HbA1c rose, blood pressure increased, lipids worsened proportionally to weight regained). The editorial accompanying the post-hoc analysis made the clinical point explicitly: 'There is a common misconception that patients can stop antiobesity medications when they reach their goal weight and maintain the weight that they lost and the cardiometabolic benefits they achieved.' The data contradicts this misconception directly.

From the chapter quick-reference block.

Indication map

Supported / plausible / speculative / avoid

Avoid

Personal or family history of MTC or MEN-2

FDA boxed warning based on rodent thyroid C-cell tumor signal. Not seen in human studies but contraindication maintained pending longer-term data.

Tirzepatide is currently the most effective FDA-approved weight loss medication and one of the few compounds on this site with A-grade evidence. For appropriate patients — meaningful obesity or type 2 diabetes — the risk/benefit is strongly favorable.

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Alternatives

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Semaglutide

Same class · Incretin Mimetic

The Most Prescribed Drug in Human History. STEP Program: -14.9% Body Weight at 68 Weeks. SELECT Trial: 20% Reduction in Major Cardiovascular Events. Grade A Evidence Across the Broadest Human Trial Program among compounds in this reference set. The Weight Rebound Question: 2/3 of Weight Returns Within 1 Year of Stopping in Controlled Trials. The Compounded Semaglutide Regulatory Crisis. What the Real-World Data Actually Shows About Discontinuation.

5-Amino-1MQ

Shared goal · weight-loss

The Compound That Raises NAD+ By Stopping the Body From Destroying It. NNMT: The Enzyme That Wastes Nicotinamide. Fat Loss Without Food Restriction in Mice. The Neelakantan Group's Research Tool Repurposed as a Longevity Drug. Zero Human Trials. 100 mg/Day Community Dose Extrapolated From Mouse IP Injections. The 1-MNA Question: The Metabolite You're Blocking Has Protective Roles in Liver and Kidney. A 2025 Cell/TPS Review Calls for Clinical Translation. Clinics Already Prescribing It Without FDA Ruling on Safety.

AOD-9604

Shared goal · weight-loss

Six Human Clinical Trials. 900+ Participants. Safety Indistinguishable From Placebo. Primary Fat Loss Endpoint Failed. WADA Banned. FDA Rejected for Compounding. The Community Uses It Anyway at Doses That Never Worked in the Trials.

Molecular weight

4,813.5 g/mol

Discovery

Eli Lilly compound; FDA approval 2022 (diabetes), 2023 (obesity)

Half-life

~5 days (~120 hours)

Typical dose

2.5 mg → titrated to 5/10/15 mg weekly

Route

SC injection, weekly

Evidence

AStrong human RCT

Key risks

GI side effects (nausea, vomiting), pancreatitis (rare), thyroid C-cell tumor warning (rodent-derived)

Last reviewed

May 2026

Best weight loss

20.9% mean at 15mg over 72 weeks (SURMOUNT-1)

A1c reduction

1.9–2.6% in T2D trials

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