Dual GIP/GLP-1 Receptor Agonist — Type 2 Diabetes / Obesity Pregnancy: Contraindicated — teratogenicity observed in animal studies; effective contraception required in women of childbearing age; stop at least 4 weeks before planned conception (long half-life ~5 days)

Tirzepatide

Brand names: Mounjaro, Zepbound

Adult dose

Dose: Starting: 2.5 mg SC weekly for 4 weeks; then 5 mg weekly; escalate by 2.5 mg every 4 weeks as tolerated to maintenance dose

Route: Subcutaneous injection (pre-filled pen)

Frequency: Once weekly (same day each week; time of day does not matter)

Max: 15 mg once weekly

Titration schedule: 2.5 → 5 → 7.5 → 10 → 12.5 → 15 mg; slow titration minimises GI side effects; do not mix with insulin in same pen; if dose missed by <4 days, give immediately; if >4 days, skip and resume on next scheduled day; MHRA approved May 2023 (T2DM: Mounjaro); obesity licence (Zepbound) — check current MHRA approval

Paediatric dose

Route: N/A

Frequency: N/A

Max: Not licensed under 18 years

No paediatric indication approved

Dose adjustments

Renal

No dose adjustment required; use with caution in severe renal impairment (eGFR <15) — limited data; GI side effects may worsen dehydration and AKI risk

Hepatic

No dose adjustment required; limited data in severe hepatic impairment

Clinical pearls

First dual GIP/GLP-1 receptor co-agonist: tirzepatide activates both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors — synergistic insulin secretion, glucagon suppression, and central appetite regulation; the GIP component increases adipocyte lipolysis and metabolic flexibility beyond GLP-1 alone
SURPASS clinical programme (T2DM): SURPASS-2 (NEJM 2021) — tirzepatide 15 mg reduced HbA1c by 2.46% (vs semaglutide 1 mg by 1.86%), weight loss 12.4 kg (vs 6.2 kg); landmark head-to-head superiority vs semaglutide; MHRA approved Mounjaro May 2023 for T2DM
SURMOUNT-1 (obesity, NEJM 2022): tirzepatide 15 mg produced 22.5% body weight reduction over 72 weeks vs 2.4% placebo — the largest weight loss seen in any pharmacotherapy trial to date, approaching surgical outcomes; 10 mg: 19.5% reduction; reshaping the obesity treatment landscape
MHRA MTC warning: based on rodent carcinogenicity studies showing C-cell thyroid hyperplasia — human relevance is uncertain as rodents have much higher GLP-1/GIP receptor density in thyroid C-cells; absolute contraindication in personal/family history of MTC or MEN2; counsel all patients; monitor TSH
Pancreatitis: causal association not definitively established but biologically plausible; counsel patients to report persistent severe abdominal pain; discontinue tirzepatide if pancreatitis confirmed; history of pancreatitis is a relative contraindication — individual risk-benefit assessment required

Contraindications

Personal or family history of medullary thyroid carcinoma (MTC)
Multiple endocrine neoplasia type 2 (MEN2)
Prior serious hypersensitivity to tirzepatide
Diabetic ketoacidosis (type 1 DM)

Side effects

Nausea (most common, 20–45% — dose-related, improves after titration)
Vomiting
Diarrhoea
Constipation
Decreased appetite
Injection site reactions
Pancreatitis (rare but serious)
Thyroid C-cell tumours (rodent data — human risk unclear)
Gallbladder disease (cholelithiasis — related to rapid weight loss)

Interactions

Oral medications — gastric emptying delay may reduce absorption; take time-sensitive drugs (e.g. oral contraceptives, antibiotics) at consistent times
Insulin secretagogues (sulfonylureas) — increased hypoglycaemia risk; reduce SU dose by 50% when starting tirzepatide
Insulin — additive hypoglycaemia risk; reduce insulin dose when initiating

Monitoring

HbA1c at 3 months (T2DM)
Body weight monthly (obesity)
Renal function if significant GI side effects or dehydration
Thyroid examination and TSH annually
Symptoms of pancreatitis
Gallbladder symptoms (rapid weight loss — gallstone risk)

Reference: BNFc; BNF 90; MHRA Approval Mounjaro May 2023; Frias et al. NEJM 2021 (SURPASS-2); Jastreboff et al. NEJM 2022 (SURMOUNT-1); SPC Mounjaro; NICE TA924 (Tirzepatide for T2DM). Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways