Serious adverse events rare among adults receiving tirzepatide in clinical trials
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Key takeaways:
- Less than 10% of adults receiving tirzepatide in clinical trials reported a serious adverse event.
- Gastrointestinal adverse events were common and increased with tirzepatide dosage.
More than one-third of adults receiving tirzepatide in clinical trials experience gastrointestinal adverse events, but adverse events leading to drug discontinuation were rare, according to study data.
In an article published in the Journal of the Endocrine Society, researchers conducted a systematic review and meta-analysis of clinical trials that reported adverse events related to tirzepatide (Mounjaro, Eli Lilly). Although gastrointestinal (GI) adverse events were common and more prevalent with higher doses of tirzepatide, adverse events such as severe hypoglycemia, acute pancreatitis, cholelithiasis and cholecystitis were rare.
“These findings increase awareness regarding the common as well as rare adverse events associated with different doses of tirzepatide,” Rahul Mishra, MD, research fellow at the Cleveland Clinic, and Rishi Raj, MD, of the department of endocrinology, diabetes and metabolism at Pikeville Medical Center in Kentucky, told Healio. “Particularly high incidence of GI adverse events, including nausea, diarrhea, dyspepsia and vomiting, can impact quality of life and treatment adherence. These should be promptly identified and appropriate management strategies, including antiemetic and antidiarrheal medications, as well as advice on dietary modifications and hydration, should be initiated.”
Raj, Mishra and colleagues conducted a search of the PubMed/MEDLINE, Embase, CINAHL, Scopus and Web of Science databases for all clinical trials reporting any adverse event related to tirzepatide published before March 12, 2022. Data were limited to trials analyzing 5 mg, 10 mg and 15 mg doses of tirzepatide and placebo. Overall safety outcomes included serious adverse events, any adverse event leading to drug discontinuation and adverse events leading to death. Specified safety outcomes included GI adverse events, gallbladder and pancreatic adverse events, appetite and weight change, hypoglycemia, allergic reactions and multisystem adverse events.
Serious adverse events reported in less than 10% of users
There were 10 studies with 6,836 adults (mean age, 58.9 years; 44.7% women) included in the meta-analysis. Nine of the 10 studies were rated as having good quality and one was given a fair rating, according to researchers.
The proportion of adults experiencing serious adverse events was 7.52% with 5 mg tirzepatide, 7.32% with 10 mg and 5.57% with 15 mg. The percentage of adults who had an adverse event leading to drug discontinuation was 7.23% in the 5 mg group, 8.68% in the 10 mg group and 10.39% in the 15 mg group. Fatal adverse events were reported in 1.07% of those receiving a 5 mg dose, 0.72% receiving 10 mg and 0.9% receiving 15 mg. There were no significant differences between any of the dose groups for severe or fatal adverse events, the researchers reported.
GI adverse events common with tirzepatide
The percentage of adults experiencing GI adverse events increased with tirzepatide dosage. GI adverse events were reported by 39.05% of those receiving 5 mg, 45.57% of those receiving 10 mg and 49.25% of adults receiving 15 mg. Nausea was the most common type of GI adverse event, followed by diarrhea, the researchers wrote.
Cholelithiasis was rare among tirzepatide users, with less than 1% reporting the condition, regardless of dosage. Acute pancreatitis was also observed in less than 1% of participants. Elevated lipase levels were more common in the tirzepatide groups compared with placebo, and adults receiving 15 mg tirzepatide had a higher prevalence of increased lipase levels (6.86%) than the 5 mg group (3.58%) or the 10 mg group (3.88%), according to the study.
The proportion of adults experiencing hypoglycemia or severe hypoglycemia was similar across all three tirzepatide groups. The incidence rate of severe hypoglycemia was less than 1% in all three tirzepatide group as well as the placebo group.
Injection site reactions were reported by 1.15% of the placebo group, 1.89% of the 5 mg tirzepatide group, 2.44% of the 10 mg tirzepatide group and 3.11% of the 15 mg tirzepatide group. The prevalence of nasopharyngitis was similar across all three tirzepatide groups, the researchers reported. Incidence of headaches climbed with tirzepatide dosage from 4% with 5 mg and 5.16% with 10 mg to 10.71% with 15 mg.
“In our meta-analysis, we found the mean age to be 58.9 years, suggesting fewer younger patients in the previous trials,” Raj and Mishra said. “Hence, future studies involving younger patients with diabetes may be necessary to more precisely assess the adverse events related to tirzepatide in different age groups. In addition, we noticed a significant heterogeneity in reporting of the adverse events, and hence, future studies should consistently report all adverse events, including the rare ones, to establish true incidence rates.”
For more information:
Rahul Mishra, MD, can be reached at mishrar2@ccf.org.
Rishi Raj, MD, can be reached at rishi.raj@pikevillehospital.org.
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