Mounjaro Side Effects: Incidence Rates Across Clinical Trials

What the Mounjaro label reports

The most complete incidence figures for Mounjaro come from Table 1 of its prescribing information. That table pools two placebo-controlled trials in adults with type 2 diabetes — SURPASS-1 (tirzepatide alone) and SURPASS-5 (tirzepatide added to basal insulin) — covering 718 patients treated with Mounjaro and 235 on placebo, with a mean exposure of 36.6 weeks [1].

Rates below are placebo first, then 5 mg, 10 mg and 15 mg once weekly [1]:

• Nausea: 4%, 12%, 15%, 18%
• Diarrhea: 9%, 12%, 13%, 17%
• Decreased appetite: 1%, 5%, 10%, 11%
• Vomiting: 2%, 5%, 5%, 9%
• Constipation: 1%, 6%, 6%, 7%
• Dyspepsia: 3%, 8%, 8%, 5%
• Abdominal pain: 4%, 6%, 5%, 5%

These are the reactions that occurred in at least 5% of Mounjaro-treated patients and more often than on placebo [1]. A wider pool of seven controlled trials, with 5,119 adults treated for a mean of 48.1 weeks, produced types and frequencies similar to Table 1 [1]. The label's figures for a cardiovascular outcomes trial of 6,647 adults with type 2 diabetes and established cardiovascular disease were also similar, with the exception of dysesthesia (0.7%), decreased appetite (17%), constipation (13%), vomiting (12%), abdominal pain (10%) and fatigue (10%) [1].

How common are GI side effects overall?

Gastrointestinal adverse reactions as a group were reported by 37.1% of patients on 5 mg, 39.6% on 10 mg and 43.6% on 15 mg, against 20.4% on placebo [1]. Severe gastrointestinal reactions occurred in 1.3%, 0.4% and 1.2% of the three dose groups versus 0.9% on placebo [1]. The label states that Mounjaro is not recommended in patients with severe gastroparesis [1].

How many people stop Mounjaro for side effects?

Gastrointestinal side effects led 3.0% of patients on 5 mg, 5.4% on 10 mg and 6.6% on 15 mg to discontinue treatment, versus 0.4% on placebo [1].

A separate, broader number appears in SURPASS-5, the 475-adult trial of tirzepatide added to insulin glargine. Treatment was discontinued early for any reason by 10% of the 5 mg group, 12% of the 10 mg group, 18% of the 15 mg group and 3% of the placebo group [2]. That measure counts every early discontinuation, not only those caused by adverse events.

Do the GI effects fade as treatment continues?

The label states that the majority of reports of nausea, vomiting and diarrhea occurred during dose escalation and decreased over time [1]. The recommended schedule — start at 2.5 mg once weekly, then increase in 2.5 mg steps after at least 4 weeks on the current dose, to a maximum of 15 mg weekly in adults and 10 mg weekly in patients 10 years and older — is specified to reduce the risk of gastrointestinal adverse reactions [1].

Serious reactions the label warns about

Acute pancreatitis. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing cases, has been observed in patients treated with GLP-1 receptor agonists or Mounjaro. The label describes the warning signs as persistent or severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by nausea or vomiting, and directs that Mounjaro be discontinued and management started if pancreatitis is suspected [1].

Gallbladder disease. In the adult placebo-controlled trials, acute gallbladder disease (cholelithiasis, biliary colic and cholecystectomy) was reported by 0.6% of Mounjaro-treated patients and 0% of placebo-treated patients [1].

Hypersensitivity. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with Mounjaro, and a known serious hypersensitivity to tirzepatide or any excipient is a contraindication [1].

Kidney injury from dehydration. Postmarketing reports describe acute kidney injury, in some cases requiring hemodialysis, mostly in patients whose nausea, vomiting or diarrhea led to volume depletion [1].

Diabetic retinopathy. Temporary worsening of diabetic retinopathy has been reported with rapid improvement in glucose control, and the label directs monitoring of patients with a history of diabetic retinopathy for progression [1].

Hypoglycemia. Mounjaro used with an insulin secretagogue such as a sulfonylurea, or with insulin, raises the risk of hypoglycemia including severe hypoglycemia; the label states that reducing the dose of the secretagogue or insulin may be necessary [1].

Pulmonary aspiration. Aspiration during general anesthesia or deep sedation has been reported in patients receiving GLP-1 receptor agonists, and the label instructs patients to inform healthcare providers about any planned surgery or procedure [1].

Thyroid C-cell tumors. The boxed warning covers this risk. Tirzepatide caused dose- and treatment-duration-dependent thyroid C-cell tumors in rats at clinically relevant exposures, and the label states that it is unknown whether Mounjaro causes thyroid C-cell tumors, including medullary thyroid carcinoma, in humans [1]. A personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 is a contraindication, and routine serum calcitonin monitoring or thyroid ultrasound is of uncertain value for early detection [1].

SURPASS-2: the direct comparison with semaglutide 1 mg

SURPASS-2 randomized 1,879 adults with type 2 diabetes on metformin to tirzepatide 5, 10 or 15 mg or semaglutide 1 mg for 40 weeks, in an open-label design [3]. Nausea was reported by 17% to 22% of tirzepatide-treated participants versus 18% on semaglutide, diarrhea by 13% to 16% versus 12%, and vomiting by 6% to 10% versus 8% [3]. SURPASS-2 compared tirzepatide only with semaglutide 1 mg once weekly [3].

Weight-management trials report separate rates

The 72-week weight-management trials of tirzepatide were run in adults with obesity under a separate label, Zepbound, and report their own adverse reaction rates. The Mounjaro label states that adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates seen in practice [1]. The diabetes-trial numbers above are the ones that belong to Mounjaro.

Heart rate and laboratory changes

Mean heart rate rose by 1 to 3 beats per minute in patients taking Mounjaro [1]. Hypotension was reported in 1.6% versus 0.1% on placebo [1]. Mean amylase rose 20% to 25% and lipase 28% to 35%, and the label states that the clinical significance of these enzyme increases is unknown in patients without signs or symptoms of pancreatitis [1].

What post-market reports cannot tell you

FDA's adverse event database collects reports submitted after a drug reaches the market, and FDA states that the existence of a report does not establish that the drug caused the event, that reports are often incomplete and unverified, and that the data cannot be used to estimate how often an event occurs [4]. Case counts for pancreatitis, gastroparesis or hair loss therefore cannot be converted into incidence rates, which is why the rates on this page come from the controlled trials [1].