The starting dose is 2.5mg, once a week, for four weeks. That detail from the UK regulator says a lot about how tirzepatide is meant to be used: slowly, with a gradual climb.
Tirzepatide, developed by Eli Lilly, is a once-weekly injection that mimics two hormones the body releases at meals, GIP and GLP-1. In the U.S. it is sold as Mounjaro for type 2 diabetes and as Zepbound for weight management. Diatribe, a diabetes publication, calls it a first-in-class drug and the first of its kind approved by the FDA.
The approvals
The FDA approved Mounjaro for type 2 diabetes in May 2022, as an addition to diet and exercise. Seeing how strongly the drug affected weight, the agency later approved it as Zepbound for people with overweight or obesity, in 2023.
In Britain, the Medicines and Healthcare products Regulatory Agency authorised a new weight-loss indication for Mounjaro on 8 November 2023, for adults aged 18 and over. Eligible patients have a BMI of 30kg/m² or more, or between 27 and 30 if they also have weight-related problems such as prediabetes, high blood pressure, high cholesterol or heart problems. The regulator said it prioritised the review because of the public health importance of tackling obesity.
How it works in the body
The drug reaches several organs, says Boston endocrinologist Dr. Florencia Halperin. Receptors in the pancreas respond by releasing more insulin, and others in the brain’s appetite centers dampen hunger. GLP-1 slows stomach emptying, so people feel full sooner and longer, while GIP acts on fat cells in several ways, Halperin explains. The MHRA described the practical effect: it regulates appetite, so patients feel less hungry and have fewer cravings.
What the trials found
For diabetes, the SURPASS trials showed an average 2% A1C reduction, and everyone on the 15 mg dose averaged an A1C below 6%.
The weight indication in Britain rests on SURMOUNT-1 and SURMOUNT-2. In SURMOUNT-1, 2,539 adults were given weekly 5mg, 10mg or 15 mg tirzepatide, or a placebo, for 72 weeks. Average weight change was -16.0% on the 5mg dose, -21.4% on 10mg, -22.5% on 15mg and -2.4% on placebo. Weight loss of at least 5% was reached by 89.4% of patients on 5 mg, 96.2% on 10 mg and 96.3% on 15 mg, against 27.9% on placebo.
Dosing, cost and cautions
The doses run 2.5mg, 5mg, 7.5mg, 10mg, 12.5mg and 15mg. After the first four weeks at 2.5mg the dose moves to 5mg, and may rise in steps of at least four weeks up to 15mg if the doctor recommends it. The pen is injected under the skin of the stomach area, thigh or upper arm. The MHRA also warned that women on oral contraceptives should add a barrier method, or switch methods, for four weeks after starting and after each dose increase.
In the U.S., Diatribe says, the list price is $1,000 or more per month. Many plans cover Mounjaro for type 2 diabetes, but coverage is thinner when it is prescribed as Zepbound for weight. Lilly’s savings card can cut costs to as little as $25 per month for those who qualify, though not for people on Medicaid or Medicare.
Sources
- MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss – GOV.UK
- Mounjaro (Tirzepatide) for Diabetes Management
- Tirzepatide (Mounjaro): Type 2 Diabetes Drug Guide
