Mounjaro Adverse Reactions

Summary of safety profile: Type 2 diabetes mellitus: In 7 completed phase 3 studies, 5119 patients were exposed to tirzepatide alone or in combination with other glucose lowering medicinal products. The most frequently reported adverse reactions were gastrointestinal disorders, including nausea (very common), diarrhoea (very common), constipation (common), and vomiting (common). In general, these reactions were mostly mild or moderate in severity and occurred more often during dose escalation and decreased over time (see Dosage & Administration and Precautions).
Weight management: In 2 completed phase 3 studies, 2519 patients were exposed to tirzepatide alone or in combination with other glucose lowering medicinal products. The most frequently reported adverse reactions were gastrointestinal disorders, including nausea (very common), diarrhoea (very common), constipation (very common), and vomiting (very common). In general, these reactions were mostly mild or moderate in severity and occurred more often during dose escalation and decreased over time (see Dosage & Administration and Precautions).
Tabulated list of adverse reactions: The following related adverse reactions from clinical studies are listed as follows by system organ class and in order of decreasing incidence (very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1000 to <1/100; rare: ≥1/10000 to <1/1000; very rare: <1/10000). Within each incidence grouping, adverse reactions are presented in order of decreasing frequency. (See Table 9.)

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Description of selected adverse reactions: Hypersensitivity reactions: Cases of anaphylactic reaction and angioedema have been rarely reported with tirzepatide during post-marketing surveillance.
Type 2 diabetes mellitus: Hypersensitivity reactions have been reported with tirzepatide in the pool of type 2 diabetes mellitus placebo-controlled trials, sometimes severe (e.g., urticaria and eczema); hypersensitivity reactions were reported in 3.2% of tirzepatide-treated patients compared to 1.7% of placebo-treated patients.
Weight management: Hypersensitivity reactions have been reported with tirzepatide in the pool of weight management placebo-controlled trials, sometimes severe (e.g., dermatitis and rash); hypersensitivity reactions were reported in 5.1% of tirzepatide-treated patients compared to 3.1% of placebo-treated patients.
Hypoglycaemia in patients with type 2 diabetes mellitus: SURPASS 1-to-5: Clinically significant hypoglycaemia [blood glucose <3.0 mmol/L (<54 mg/dL) or severe hypoglycaemia (requiring the assistance of another person)] occurred in 10 to 14% (0.14 to 0.16 events/patient year) of patients when tirzepatide was added to sulphonylurea and in 14 to 19% (0.43 to 0.64 events/patient year) of patients when tirzepatide was added to basal insulin.
The rate of clinically significant hypoglycaemia when tirzepatide was used as monotherapy or when added to other oral antidiabetic medicinal products was up to 0.04 events/patient year (see Table 9, Dosage & Administration, Precautions, and Pharmacology: Pharmacodynamics under Actions).
In phase 3 clinical studies, 10 (0.2%) patients reported 12 episodes of severe hypoglycaemia. Of these 10 patients, 5 (0.1%) were on a background of insulin glargine or sulphonylurea who reported 1 episode each.
SURMOUNT-2: Clinically significant hypoglycaemia [blood glucose <3.0 mmol/L (<54 mg/dL)] occurred in 4.2% of tirzepatide-treated patients versus 1.3% of placebo-treated patients.
The rate of clinically significant hypoglycaemic episodes was similar across tirzepatide 10 mg and 15 mg (4.3, and 6.1 events per 100 patient years of exposure, respectively) and the placebo-treated group (9.7 events per 100 patient years of exposure). The risk of hypoglycaemia was increased when tirzepatide was used with a sulfonylurea.
No cases of severe hypoglycaemia were reported.
Gastrointestinal adverse reactions: Type 2 diabetes mellitus: In the placebo-controlled type 2 diabetes mellitus phase 3 studies, gastrointestinal disorders were dose-dependently increased for tirzepatide 5 mg (37.1%), 10 mg (39.6%) and 15 mg (43.6%) compared with placebo (20.4%). Nausea occurred in 12.2%, 15.4% and 18.3% versus 4.3% and diarrhoea in 11.8%, 13.3% and 16.2% versus 8.9% for tirzepatide 5 mg, 10 mg, and 15 mg versus placebo. Gastrointestinal adverse reactions were mostly mild (74%) or moderate (23.3%) in severity. The incidence of nausea, vomiting, and diarrhoea was higher during the dose escalation period and decreased over time.
More patients treated with tirzepatide 5 mg (3.0%), 10 mg (5.4%) and 15 mg (6.6%) discontinued permanently due to the gastrointestinal event compared with placebo (0.4%).
Weight management: In the placebo-controlled weight management phase 3 studies, gastrointestinal disorders were 55.6% for tirzepatide 5 mg, 55.8% for tirzepatide 10 mg and 55.6% for tirzepatide 15 mg compared with placebo 29.7%. Nausea occurred in 24.6%, 29.0% and 28.0% versus 8.5% and diarrhoea in 18.7%, 20.8% and 22.5% versus 7.8% for tirzepatide 5 mg, 10 mg and 15 mg versus placebo. Gastrointestinal adverse reactions were mostly mild (61.0%) or moderate (34.4%) in severity. The incidence of nausea, vomiting, and diarrhoea was higher during the dose escalation period and decreased over time.
More patients in the tirzepatide 5 mg (1.9%), 10 mg (3.3%) and 15 mg (4.3%) groups compared to the placebo group (0.5%) discontinued permanently due to the gastrointestinal event.
Gallbladder related disorders: Type 2 diabetes mellitus: In the placebo-controlled type 2 diabetes mellitus phase 3 studies, cholelithiasis was reported in 0.3% of tirzepatide-treated patients and 0 placebo-treated patients.
Weight management: In SURMOUNT-1 and -2, acute gallbladder disease was reported by 2.0% of tirzepatide-treated patients and 1.7% of placebo-treated patients. These acute gallbladder events were positively correlated with weight reduction. The overall incidence of cholecystitis and cholecystitis acute was 0.7% and 0.2% for tirzepatide- and placebo-treated patients, respectively. Cholelithiasis was reported by 1.1% of tirzepatide-treated patients and 1.0% of placebo-treated patients.
Hair loss: Weight management: In SURMOUNT-1 and SURMOUNT-2, hair loss was reported in 4.7% of patients treated with tirzepatide and in 0.84% of patients treated with placebo. The events were mainly of mild severity and most patients recovered while on continued treatment. No tirzepatide patients discontinued drug or study due to hair loss.
Immunogenicity: There was no identified clinically significant effect of anti-tirzepatide antibodies on pharmacokinetics or effectiveness of tirzepatide.
Type 2 diabetes mellitus: 5025 tirzepatide-treated patients in the type 2 diabetes mellitus phase 3 clinical studies were assessed for anti-drug antibodies (ADAs). Of these, 51.1% developed treatment-emergent (TE) ADAs during the on-treatment period. In 38.3% of the assessed patients, TE ADAs were persistent (ADAs present for a period of 16-weeks or greater). 1.9% and 2.1% had neutralizing antibodies against tirzepatide activity on the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, respectively and 0.9% and 0.4% had neutralising antibodies against native GIP and GLP-1, respectively.
Weight management: 2467 tirzepatide-treated patients in weight management phase 3 clinical studies were assessed for anti-drug antibodies (ADAs). Of these, 64.5% developed treatment-emergent (TE) ADAs during the on-treatment period. In 51.5% of the assessed patients, TE ADAs were persistent (ADAs present for a period of 16 weeks or greater). 2.8% and 2.7% had neutralizing antibodies against tirzepatide activity on the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, respectively and 0.8% and 0.1% had neutralising antibodies against native GIP and GLP-1, respectively.
Heart rate: Type 2 diabetes mellitus: In the placebo-controlled type 2 diabetes mellitus, phase 3 studies, treatment with tirzepatide resulted in a maximum mean increase in heart rate of 3 to 5 beats per minute. The maximum mean increase in heart rate in placebo-treated patients was 1 beat per minute.
The incidence of patients who had a change of baseline heart rate of >20 bpm for 2 or more consecutive visits was 2.1%, 3.8% and 2.9%, for tirzepatide 5 mg, 10 mg and 15 mg, respectively, compared with 2.1% for placebo.
Small mean increases in PR interval were observed with tirzepatide when compared to placebo (mean increase of 1.4 to 3.2 msec and mean decrease of 1.4 msec respectively). No difference in arrhythmia and cardiac conduction disorder treatment emergent events were observed between tirzepatide 5 mg, 10 mg, 15 mg and placebo (3.8%, 2.1%, 3.7% and 3% respectively).
Weight management: In the placebo-controlled weight management clinical trials, treatment with tirzepatide resulted in a mean increase in heart rate of 1 to 3 beats per minute compared to no increase in placebo-treated patients.
Injection site reactions: Type 2 diabetes mellitus: In the placebo-controlled type 2 diabetes mellitus phase 3 studies, injection site reactions were 3.2% for tirzepatide compared with 0.4% for placebo.
Overall, in the phase 3 studies, the most common signs and symptoms of injection site reactions were erythema and pruritus. The maximum severity of injection site reactions for patients was mild (90%) or moderate (10%). No injection site reactions were serious.
Weight management: In the placebo-controlled weight management phase 3 studies, injection site reactions were 7.6% for tirzepatide compared with 1.8% for placebo. The most common signs and symptoms of injection site reactions were erythema and pruritus. All events were reported as mild to moderate in severity.
Pancreatic enzymes: The clinical significance of elevations in amylase or lipase with tirzepatide is unknown in the absence of other signs and symptoms of pancreatitis.
Type 2 diabetes mellitus: In the placebo-controlled type 2 diabetes mellitus phase 3 studies, treatment with tirzepatide resulted in mean increases from baseline in pancreatic amylase of 33% to 38% and lipase of 31% to 42%. Placebo treated patients had an increase from baseline in amylase of 4% and no changes were observed in lipase.
Weight management: In the placebo-controlled weight management clinical trials, treatment with tirzepatide resulted in mean increases from baseline in serum pancreatic amylase concentrations of 20% to 25% and serum lipase concentrations of 28% to 35%. Placebo-treated patients had a mean increase from baseline in pancreatic amylase of 2.1% and serum lipase of 5.8%.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to the Drug Office, Department of Health.