GLP-1 & incretin
Tirzepatide
A dual GIP and GLP-1 receptor agonist approved for type 2 diabetes and weight management, with larger average weight loss than GLP-1-only agonists in trials.
What it is
Tirzepatide is a synthetic 39-amino-acid peptide that acts on two gut-hormone receptors at once: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1. It is built on the GIP sequence with additions that extend its half-life to about five days, allowing once-weekly dosing. It is a prescription medicine (Mounjaro, Zepbound).
How it works
- 1
Binds both GIP and GLP-1 receptors, with receptor signalling biased toward the GIP receptor.
- 2
Increases insulin release and lowers glucagon in a glucose-dependent way.
- 3
Slows gastric emptying and reduces appetite through hypothalamic signalling.
- 4
GIP receptor activity appears to add to the effect on fat mass and possibly on how the body handles fat.
- 5
Net effect: lower blood glucose and substantially reduced body weight.
What it's studied for
Reported and studied effects
- HbA1c reduction of up to about 2.4 percentage points in trials
- Mean weight loss of roughly 20% at 72 weeks with the highest dose (SURMOUNT-1)
- Greater average weight loss than semaglutide 1 mg in a head-to-head diabetes trial (SURPASS-2)
- Improved blood pressure and lipid markers in trials
- Reduced apnoea-hypopnoea index in obesity with sleep apnoea
Research protocol notes
Research context onlyResearch context only — tirzepatide is a prescription medicine and dosing is set by a doctor. Trial protocols escalated from 2.5 mg to 5–15 mg subcutaneously once weekly in 2.5 mg steps every four weeks, over 40–72 weeks. This is not a dosing suggestion.
These figures are described so you can understand what researchers did. They are not a dose, a schedule, or a suggestion — and they are not a substitute for a doctor.
Possible side effects and contraindications
Safety profile
Possible side effects
- Nausea, diarrhoea, vomiting and constipation, worst during dose escalation
- Reflux, belching and indigestion
- Reduced appetite and reduced food intake
- Injection-site reactions, fatigue and hair loss, all listed among the most common reactions in the FDA label
- Gallbladder disease
- Pancreatitis (rare; serious and sometimes fatal cases reported after marketing)
- Thyroid C-cell tumours in rodents — human relevance unknown
Contraindications and cautions
- Personal or family history of medullary thyroid carcinoma
- Multiple endocrine neoplasia syndrome type 2
- Pregnancy
- Known serious hypersensitivity to tirzepatide
- Active or suspected pancreatitis needs medical review
A side-effect list is never complete, and these are not the only situations that warrant caution. Anything unexpected, or anything you are unsure about, should be discussed with a doctor before use.
Evidence assessment
Large randomised controlled trials across two full clinical programmes, consistent replication, pre-specified endpoints and regulatory approval.
References
- 01Jastreboff et al., Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1), NEJM 2022
- 02Frías et al., Tirzepatide versus Semaglutide Once Weekly in Type 2 Diabetes (SURPASS-2), NEJM 2021
- 03European Medicines Agency — Mounjaro product information
- 04FDA — Zepbound (tirzepatide) prescribing information
References link to published literature, regulator pages or literature indexes. Where a link points to a search, it collects the peer-reviewed work on that molecule rather than a single study.
Related
Related peptides
Other entries in GLP-1 & incretin.
GLP-1 & incretin
Cagrilintide
A long-acting amylin analogue that slows digestion and reduces appetite, studied alone and combined with semaglutide for obesity.
GLP-1 & incretin
Dulaglutide
A once-weekly GLP-1 receptor agonist approved for type 2 diabetes, with proven cardiovascular benefit in people at high risk.
GLP-1 & incretin
Exenatide
A GLP-1 receptor agonist derived from Gila monster saliva, approved for type 2 diabetes in twice-daily and once-weekly forms.