Using the efficacy estimand, mean weight loss was 13.2% with eloralintide 3 mg plus tirzepatide 5 mg, 19.4% with eloralintide 6 mg plus tirzepatide 5 mg, 19.9% with eloralintide 6 mg plus tirzepatide 10 mg, and 23.3% with eloralintide 9 mg plus tirzepatide 15 mg. Corresponding HbA1c reductions were 2.2%, 2.7%, 2.6%, and 2.9%, respectively. Tirzepatide 15 mg alone yielded weight loss of 14.8% and an HbA1c reduction of 2.4%; eloralintide alone produced weight loss of 8.2% to 12.3%, and placebo produced 3.0% and 0.3%, respectively.2
Tolerability and Titration
The most common adverse events were gastrointestinal, generally mild or moderate, and occurred primarily during dose escalation, more often in the combination arms than with either agent alone. Discontinuation due to adverse events ranged from 10.8% to 27.0% across EloraTZP arms, compared with 0% to 10.8% with eloralintide, 2.9% with tirzepatide, and 16.7% with placebo.2
Those events were more frequent when both agents were initiated and escalated at the same time, according to lead author Liana K. Billings, MD, MMSc, vice chair of research in the Department of Medicine at Endeavor Health and clinical associate professor in medicine at the University of Chicago Pritzker School of Medicine.
“If I were using this approach with my patients, I would set expectations from the outset that gastrointestinal symptoms may occur and discuss dietary and lifestyle strategies, as well as short-term medications for symptom relief when needed,” Billings told Pharmacy Times. “Importantly, if tolerability is a concern, these data also support a sequential approach. When participants first escalated tirzepatide to 15 mg and then added eloralintide, gastrointestinal adverse event rates were similar to tirzepatide alone, while still achieving excellent weight and glucose-lowering efficacy.”
Implications for Treatment Sequencing
“Amylin agonists give us another option for treating obesity and T2D and an opportunity to further individualize therapy,” Billings said. “In this trial, adding eloralintide after participants had escalated tirzepatide to 15 mg led to a further increase in the trajectory of weight loss, suggesting that eloralintide could be added when additional weight or HbA1c reduction is needed.”
Although the reverse sequence was not studied, Billings said the efficacy and tolerability of eloralintide alone raise the possibility of starting with eloralintide and adding tirzepatide later if additional efficacy is needed. When pharmacists review regimens for patients with T2D, they should note that tirzepatide labeling says hypoglycemia risk may be higher with concomitant insulin or a sulfonylurea. That matters as additional glucose-lowering mechanisms are layered on.2
