Mounjaro's first label sets a six-dose ladder from 2.5 mg to 15 mg

The U.S. Food and Drug Administration approved Eli Lilly's Mounjaro (tirzepatide) injection on May 13, 2022, as an add-on to diet and exercise to improve blood sugar control in adults with type 2 diabetes ^[1]. It is the first and only FDA-approved medicine that activates receptors for both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) in a single molecule ^[1].

Lilly said Mounjaro will be sold in six doses — 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg — delivered once weekly in an auto-injector pen with a pre-attached, hidden needle that patients do not need to handle or see ^[1]. The company's announcement lists those six strengths but does not spell out the week-by-week escalation schedule, which appears in the prescribing information itself.

What the trials showed

Approval rested on the phase 3 SURPASS program, which began in late 2018 and included five global registration trials plus two regional trials in Japan, running 40 to 52 weeks ^[1]. Comparators included injectable semaglutide 1 mg, insulin glargine and insulin degludec ^[1]. Across the program, average A1C reductions ranged from 1.8% to 2.1% for the 5 mg dose and from 1.7% to 2.4% for the 10 mg and 15 mg doses ^[1].

In SURPASS-2, the head-to-head against injectable semaglutide 1 mg in people taking at least 1,500 mg/day of metformin, A1C fell an average of 2.0% (5 mg), 2.2% (10 mg) and 2.3% (15 mg) from a baseline of 8.3%, compared with 1.9% for semaglutide ^[1]. Weight, a key secondary endpoint, dropped an average of 17 lb, 21 lb and 25 lb on the three tirzepatide doses from a baseline of 207 lb, versus 13 lb for semaglutide ^[1]. Across all SURPASS studies, average weight loss ranged from 12 lb at 5 mg to 25 lb at 15 mg ^[1]. Mounjaro was not approved for weight loss ^[1].

Warnings on the label

The label carries a boxed warning about thyroid C-cell tumors ^[1]. Mounjaro is contraindicated in people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2 ^[1]. It has not been studied in people with a history of pancreatitis, is not indicated for type 1 diabetes, and its safety and effectiveness in children under 18 are not known ^[1].

Side effects reported in at least 5% of patients were nausea, diarrhea, decreased appetite, vomiting, constipation, indigestion and abdominal pain ^[1]. The label also flags pancreatitis, low blood sugar (a higher risk when combined with a sulfonylurea or insulin), serious allergic reactions, kidney problems tied to dehydration from vomiting and diarrhea, severe stomach problems, vision changes and gallbladder problems ^[1].

Why it matters for patients

The six-step ladder means the dose a person starts on is not the dose studied for efficacy — SURPASS tested 5 mg, 10 mg and 15 mg, while 2.5 mg, 7.5 mg and 12.5 mg exist as steps along the way ^[1]. That staged approach is how the label handles the gastrointestinal side effects that dominate the common-reactions list ^[1].

Cost and coverage were open questions at approval. A Lilly spokesperson said no price had been announced ^[2], and the company said it planned to offer a savings card for people who qualify ^[1]. Advisers to the Institute for Clinical and Economic Review, an independent drug cost watchdog, concluded there was not enough evidence that tirzepatide provides a significant health benefit over Ozempic (semaglutide) ^[2] — a judgment that can shape what insurers agree to pay.

"Given the challenges many patients experience in achieving their target blood sugar goals, today's approval of Mounjaro is an important advance in the treatment of type 2 diabetes," said Patrick Archdeacon, associate director of the diabetes division in FDA's Center for Drug Evaluation and Research ^[2].

What happens next

Lilly said Mounjaro was expected to reach U.S. pharmacies "in the coming weeks" after the May 13 approval ^[1][2]. Tirzepatide was also under regulatory review for type 2 diabetes in Europe, Japan and several other markets ^[1]. Lilly reported positive obesity trial data for the molecule in April 2022, but a weight-loss indication was not part of this approval ^[1][2].