Gastrointestinal adverse events, hypoglycemia seen in minority
The most common treatment-emergent adverse events in the tirzepatide groups versus placebo were gastrointestinal, including diarrhea (12%-21% vs. 10%), nausea (13%-18% vs. 2.5%), vomiting (7%-13% vs. 2.5%), and decreased appetite (7%-14% vs. 1.7%). Most of these adverse events were mild to moderate in intensity and decreased over time in the tirzepatide groups.
There were no deaths in the study. Serious adverse events were reported by 8%-11% in the tirzepatide groups, compared with 8% in the placebo group. Drug discontinuation due to adverse events occurred in 6.0%, 8.4%, and 10.8% of the 5-mg, 10-mg, and 15-mg dose groups, respectively, versus 2.5% in the placebo group.
Rates of hypoglycemia (less than or equal to 70 mg/dL) ranged from 14.2% to 19.3% with tirzepatide versus 12.5% with placebo. There were three episodes of severe hypoglycemia (less than 54 mg/dL), two with 10 mg tirzepatide and one with 15 mg tirzepatide.
Editorial raises questions
In his editorial, Dr. Chipkin writes that the study “demonstrated that use of tirzepatide was associated with significant reductions in A1c and weight in a fairly homogeneous cohort of patients with type 2 diabetes who were receiving insulin glargine with or without metformin.”
“The protocol answered questions about efficacy but left open questions about generalizability and effectiveness in different populations, especially patients with certain complications or comorbid chronic diseases.” He also notes that younger adults and Black patients were not well-represented.
And the study didn’t allow for dividing up the glargine dose or for adding short-acting insulin before meals or any other pre-meal medications and “thus may represent a departure from usual care” in the setting of rising glucose levels.
The authors themselves acknowledge that “the postprandial glucose excursions observed in the placebo group suggest an additional prandial intervention was likely needed in some patients, despite the strict inclusion criteria and the treat-to-target-approach used in the study.”
Dr. Chipkin concludes that “although patients are likely to embrace a medication with weight loss outcomes, the protocol also leaves unanswered questions about reducing insulin and evaluating the comparative risk of adverse effects.”
The study was sponsored by Eli Lilly. Dr. Dahl has reported receiving personal fees from Eli Lilly during the conduct of the study and personal fees from Afimmune, Novo Nordisk, and Novartis outside the submitted work. Dr. Chipkin has reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.