What it is
Tirzepatide is a lab-made peptide that imitates two gut hormones at once: GIP and GLP-1. Both are released after a meal and both tell the pancreas to make insulin. GLP-1 also slows the stomach and reduces appetite. Semaglutide copies only GLP-1. Tirzepatide copies both, which appears to be why it produces larger weight loss in head-to-head trials.
Eli Lilly sells it as Mounjaro for type 2 diabetes and as Zepbound for weight management and sleep apnoea. It is the same molecule in both boxes. It is a once-weekly injection.
Tirzepatide is a 39-residue synthetic peptide built on the GIP backbone, with Aib substitutions at positions 2 and 13 for DPP-4 resistance and a C20 fatty diacid on Lys20 via a γGlu-2xOEG linker for albumin binding. It is a full agonist at the GIP receptor and a biased partial agonist at the GLP-1 receptor, with lower β-arrestin recruitment than native GLP-1. Plasma half-life is about 5 days.
The pharmacological rationale is that GIP receptor agonism adds to GLP-1-driven weight loss through effects on adipose tissue insulin sensitivity and central appetite circuits, and may partly offset GLP-1 nausea. Whether the GIP component acts as an agonist or effectively as a desensitiser in vivo remains debated in the literature.
Who made it and when
Lilly chemists including Tamer Coskun designed it in the mid-2010s under the code LY3298176. The first full description was published in 2018. FDA approval for diabetes came in May 2022, for weight management in November 2023 and for sleep apnoea in December 2024. In December 2025 the diabetes approval was extended to children 10 and older, and in August 2026 Mounjaro gained a heart-risk-reduction indication. Lilly holds the patents into the 2030s.
Coskun and colleagues reported the compound in Molecular Metabolism in 2018, describing its balanced GIP/GLP-1 receptor pharmacology and rodent efficacy. The core compound patent, US 9,474,780 (priority January 2015), is assigned to Eli Lilly. Approval history: Mounjaro (NDA 215866) 2022-05-13; Zepbound (NDA 217806) 2023-11-08; OSA indication 2024-12-20; Mounjaro pediatric type 2 diabetes (10 years and older, maximum 10 mg weekly) 2025-12-19; Mounjaro cardiovascular risk reduction in type 2 diabetes, based on SURPASS-CVOT, 2026-08-27. SURPASS-CVOT data were added to the Zepbound label on 2026-08-26 without a new Zepbound indication.
What the data say
In people with obesity and no diabetes, the highest dose cut body weight by about 21% over 72 weeks, against about 3% on placebo. In a direct comparison, tirzepatide beat semaglutide by roughly 6 percentage points. In diabetes it lowered blood sugar more than semaglutide 1 mg. It reduced sleep-apnoea events, reduced heart-failure events in people with obesity, and matched dulaglutide, an older diabetes drug, on heart attacks, strokes and cardiovascular deaths in a large outcomes trial.
SURMOUNT-1 (n=2,539) reported placebo-adjusted weight change of −11.9 to −17.8 percentage points at 72 weeks. SURMOUNT-5 (n=751) reported −20.2% vs −13.7% for semaglutide at maximum tolerated dose, a treatment difference of −6.5 points. SURPASS-2 showed superior HbA1c and weight reduction vs semaglutide 1 mg at all three doses. SURMOUNT-OSA reported AHI reductions of about 25–29 events per hour. SUMMIT reported a hazard ratio of 0.62 for the composite of cardiovascular death or worsening heart failure in HFpEF with obesity. SURPASS-CVOT (n=13,299, median follow-up about 4 years) met non-inferiority vs dulaglutide on 3-point MACE with a hazard ratio of 0.92 (95.3% CI 0.83–1.01); superiority was not shown (Nicholls et al., NEJM 2025).
Regulatory picture
Tirzepatide is fully FDA approved under its two brand names. What is not approved is anyone else’s version. During the 2022–2024 shortage, compounding pharmacies could legally make copies. The FDA declared the shortage over in December 2024 and set February and March 2025 deadlines for compounders to stop. Since then the FDA has sent warning letters to sellers of “compounded” or “research” tirzepatide, and in February 2026 it announced steps to restrict the raw ingredient used in mass-marketed compounded copies.
Tirzepatide is a component of FDA-approved products and is not on, and does not need to be on, the 503A bulk drug substances list. Compounding of essentially-copies is permitted only while the product is on the FDA drug shortage list. The FDA removed tirzepatide from the shortage list on 2024-10-02, re-evaluated after litigation by the Outsourcing Facilities Association, and confirmed the decision on 2024-12-19, with enforcement discretion ending 2025-02-18 (503A) and 2025-03-19 (503B). FDA confirmed in April 2026 that tirzepatide is on neither the shortage list nor the 503B bulks list. Personalised compounded formulations that differ materially from the approved product remain a contested area, and FDA’s February 2026 announcement signalled tighter control of GLP-1 active ingredients destined for non-approved compounded drugs.
