Mounjaro (Tirzepatide) Vomiting Severity Grading: A Clinical Rubric for Patients and Providers

What the label reports

The vomiting figures come from a pool of two placebo-controlled trials in adults with type 2 diabetes, SURPASS-1 (monotherapy) and SURPASS-5 (basal insulin with or without metformin): 718 adults exposed to Mounjaro, mean exposure 36.6 weeks, with 235 on placebo and 237, 240 and 241 on 5, 10 and 15 mg [1]. Vomiting was reported by 2% on placebo, 5% at 5 mg, 5% at 10 mg and 9% at 15 mg [1].

Three further label figures put that in context:

• Severe gastrointestinal adverse reactions: 1.3% at 5 mg, 0.4% at 10 mg and 1.2% at 15 mg, versus 0.9% on placebo [1].
• Gastrointestinal adverse reactions of any severity: 20.4% on placebo versus 37.1%, 39.6% and 43.6% on 5, 10 and 15 mg [1].
• Discontinuation because of a gastrointestinal reaction: 3.0%, 5.4% and 6.6% versus 0.4% on placebo [1].

In the cardiovascular outcomes trial of 6,647 adults with type 2 diabetes and established cardiovascular disease, vomiting was reported by 12% of those on Mounjaro [1]. The label cautions that adverse reaction rates from different trials cannot be compared directly [1].

In SURPASS-2, which compared tirzepatide with semaglutide 1 mg in 1,879 adults with type 2 diabetes over 40 weeks, vomiting was reported in 6% to 10% of the tirzepatide arms and in 8% of those on semaglutide [2]. A review of tirzepatide in type 2 diabetes describes its adverse events as mostly mild to moderate in severity, with gastrointestinal events the most common [3].

When it happens

The label states that the majority of reports of nausea, vomiting and/or diarrhea occurred during dose escalation and decreased over time [1]. It starts Mounjaro at 2.5 mg once weekly and allows increases in 2.5 mg steps after at least 4 weeks on the current dose if additional glycemic control is needed, to a maximum of 15 mg weekly in adults and 10 mg weekly in children 10 and older [1].

Label warnings that apply to severe vomiting

Dehydration and kidney injury. The label warns of acute kidney injury from volume depletion. Most reported cases occurred in patients who had gastrointestinal reactions leading to dehydration such as nausea, vomiting or diarrhea, and the label advises monitoring renal function in patients reporting reactions that could lead to volume depletion, especially during initiation and dose escalation [1].

Severe or persistent abdominal pain. The label says persistent or severe abdominal pain, sometimes radiating to the back, with or without nausea or vomiting, may be a sign of acute pancreatitis. If pancreatitis is suspected, it says to discontinue Mounjaro and initiate appropriate management [1].

Severe gastroparesis. Mounjaro is not recommended in patients with severe gastroparesis [1].

Is 15 mg really worse than 10 mg?

The label's vomiting rates are 5% at 5 mg, 5% at 10 mg and 9% at 15 mg, and severe gastrointestinal reactions were 1.3%, 0.4% and 1.2% [1]. The highest dose carries the highest vomiting rate in this pool, but the rate is the same at 5 and 10 mg and the severe-reaction rates do not climb in step with dose [1].