Tirzepatide
Mounjaro · Zepbound
Dual GIP/GLP-1 agonist producing the largest weight reduction of any approved agent to date.
Class
GIP and GLP-1 dual receptor agonist
Half-life
~5 days (once-weekly dosing)
Evidence
Randomized human trials
Randomized human trials
Supported by randomized controlled trials in humans. Several compounds at this level are FDA-approved for specific indications.
Overview
Tirzepatide is a single 39-amino-acid peptide engineered to activate two incretin receptors at once: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1. It is biased toward the GIP receptor, and the prevailing hypothesis is that GIP agonism both amplifies the metabolic effect and improves GI tolerability relative to pure GLP-1 agonism at equivalent efficacy.
In SURMOUNT-1, participants on 15 mg weekly lost a mean 20.9% of body weight over 72 weeks — a magnitude previously only seen with bariatric surgery. SURPASS trials in type 2 diabetes showed HbA1c reductions exceeding 2 percentage points, and SURMOUNT-OSA demonstrated meaningful improvement in obstructive sleep apnea severity.
Its risk profile closely mirrors semaglutide's, including the same boxed warning for thyroid C-cell tumours. The larger effect size does not come with a materially different safety burden, but the GI side effects during titration are real and dose-dependent.
How it works
- Agonises GLP-1 receptors — glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying, central appetite suppression.
- Agonises GIP receptors in adipose tissue and the CNS, which appears to improve insulin sensitivity and lipid handling beyond GLP-1 alone.
- GIP receptor activity in the brain may also reduce nausea signalling, partially offsetting the GI burden of GLP-1 agonism.
- Net effect is a larger caloric deficit and greater improvement in insulin sensitivity than single-agonist therapy.
What the research shows
Researched effects
- Mean 20.9% body weight reduction at 72 weeks (SURMOUNT-1, 15 mg)
- HbA1c reduction of 2.0–2.4 percentage points in type 2 diabetes (SURPASS program)
- Superior to semaglutide 1 mg on both weight and HbA1c in the head-to-head SURPASS-2 trial
- Roughly 60% reduction in apnea-hypopnea index in obesity-related sleep apnea (SURMOUNT-OSA)
- Improvement in hepatic fat fraction and cardiometabolic risk markers
Limitations & what it won't do
- Same regain pattern on discontinuation — SURMOUNT-4 showed substantial weight regain after withdrawal.
- Lean mass loss is proportionally similar to semaglutide; resistance training and protein remain non-negotiable.
- No completed cardiovascular outcomes trial equivalent to SELECT at time of writing.
Dosing protocols
These ranges reflect published trials and community protocols. They are reference information, not a prescription. Doses are per injection unless noted.
Standard clinical titration
2.5 mg → 15 mg2.5 mg is an initiation dose for tolerability, not a treatment dose. Many people find an effective plateau at 7.5–10 mg and never need 15 mg.
Conservative micro-titration
1.25 mg → 2.5 mgUsed by people highly sensitive to GI effects. Extends time to efficacy but improves adherence.
Reconstitution & measuring your dose
Handling
- Typical vial sizes
- 10 · 20 · 30 · 40 · 50 · 60 mg
- Suggested BAC water
- 2 mL
- Storage
- Lyophilised powder refrigerated at 2–8 °C, protected from light.
- After reconstitution
- Reconstituted: approximately 28 days refrigerated. Do not freeze. Discard if discoloured or cloudy.
Why 2 mL? A 30 mg vial in 2 mL gives 15 mg/mL — 2.5 mg lands on ~17 units and 15 mg on 100 units of a U-100 syringe. For finer control on low doses, reconstituting a 10 mg vial in 2 mL (5 mg/mL) puts 2.5 mg on a clean 50 units.
Dose calculator
Draw to
25units
= 0.25 mL · 100 mcg per unit
Concentration
10000 mcg/mL
Doses per vial
8
Side effects
Common
- Nausea, most pronounced in the 48 hours after a dose increase
- Diarrhoea and constipation, often alternating
- Vomiting
- Decreased appetite to the point of under-eating protein
- Fatigue
- Injection-site reactions
Serious / rare
- Acute pancreatitis
- Gallbladder disease and cholelithiasis
- Severe gastroparesis or ileus
- Acute kidney injury from volume depletion
- Hypoglycemia when combined with insulin or sulfonylureas
Contraindications & interactions
Do not use if you have
- Medullary thyroid carcinoma or MEN2 (personal or family)
Boxed warning. Rodent thyroid C-cell tumour signal makes personal or family history of MTC or MEN2 an absolute contraindication.
- Pregnant, breastfeeding, or trying to conceive
Contraindicated. Discontinue well in advance of a planned pregnancy.
- Pancreatitis history
Prior pancreatitis is a contraindication given the incretin-class pancreatitis signal.
Use caution if you have
- Gastroparesis or delayed gastric emptying
Delayed gastric emptying is a core mechanism — additive with existing gastroparesis.
- Gallbladder disease or gallstones
Rapid weight loss markedly increases gallstone formation risk.
- Diabetic retinopathy or eye disease
Rapid glycemic correction can transiently worsen retinal disease.
- Type 1 diabetes
Not indicated in type 1 diabetes; off-label use requires close insulin management.
- Kidney disease
GI fluid losses on a compromised baseline can precipitate AKI.
Medication interactions
- avoidInsulin — Serious hypoglycemia risk without prescriber-managed insulin reduction.
- avoidSulfonylureas — Additive hypoglycemia risk; requires supervised dose reduction.
- avoidGLP-1 / GIP agonists — Tirzepatide already contains GLP-1 agonism. Never stack.
- monitorMetformin — Commonly co-prescribed; watch additive GI effects.
- cautionHormonal contraceptives / HRT — Oral contraceptive absorption can be reduced during titration — use a backup method for 4 weeks after each increase.
- monitorThyroid hormone — Recheck TSH once at a stable dose.
Don't stack with
- Semaglutide — Duplicate GLP-1 agonism with compounding GI and pancreatitis risk.
- Retatrutide — Overlapping incretin agonism — additive risk, no additive benefit.
- Liraglutide — Duplicate GLP-1 agonism.
What to monitor
- HbA1c and fasting glucose at baseline and quarterly
- Body composition scan (DEXA or BIA) to track lean mass retention
- Renal function if GI losses are significant
- Baseline retinal exam in diabetics
- Protein intake ≥1.6 g/kg plus 2–3 resistance sessions weekly
Commonly combined with
References
- SURMOUNT-1 — Tirzepatide Once Weekly for the Treatment of ObesityNEJM 2022;387:205-216
- SURPASS-2 — Tirzepatide versus Semaglutide Once WeeklyNEJM 2021;385:503-515
- SURMOUNT-OSA — Tirzepatide for Obstructive Sleep ApneaNEJM 2024;390:2200-2212
Research & educational information only — not medical advice.
You must be 18 or older to use this site. The peptides described are presented as research chemicals intended for research purposes only. Most are not approved by the FDA for human use. Dosing ranges reflect what has appeared in the scientific literature or community protocols and are not prescriptions. Nothing here replaces evaluation by a licensed physician who knows your full medical history.
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