Lilly’s EloraTZP Tops Tirzepatide Alone on Weight Loss, A1C in Study

Eli Lilly says its experimental combination of the amylin agonist EloraTZP (eloralintide and tirzepatide) produced greater weight loss and A1C reductions than high-dose tirzepatide (Lilly’s Zepbound ) alone in a Phase 2b trial of adults with obesity or overweight and Type 2 diabetes, prompting the company to advance the combination into Phase 3 testing.

In the 367-patient, 48-week study, the highest-dose EloraTZP regimen — eloralintide 9 mg plus tirzepatide 15 mg — produced average weight loss of 23.3%, or 54.1 pounds, compared with 14.8%, or 34.4 pounds, for tirzepatide 15 mg alone, according to the company. A1C fell by an average of 2.9% with the highest-dose combination, versus 2.4 points with tirzepatide alone. Participants entered the study with an average A1C of 8.1% and body weight of 232.4 pounds, it says.

Other EloraTZP dose combinations produced weight reductions ranging from 13.2% to 19.9% and A1C reductions of 2.2 to 2.7 percentage points. Eloralintide alone produced weight loss of up to 12.3% and A1C reductions of up to 1.4 percentage points, Lilly notes.

The most common adverse events were gastrointestinal and generally mild or moderate, although they occurred more frequently with the combination than with either drug alone. Adverse-event-related discontinuation rates ranged from 10.8% to 27% in the EloraTZP groups, compared with 2.9% for tirzepatide alone.

The combination's tolerability could be an important issue heading into Phase 3.

At an EASD press conference Monday, Lilly Cardiometabolic Health President Ken Custer said the Phase 2 design made it difficult to determine the combination's ultimate tolerability because patients were escalating doses of two drugs during the 48-week study, according to BioSpace. Lilly plans to use an optimized escalation schedule in Phase 3

Lilly plans to begin Phase 3 trials in the fourth quarter. Eloralintide is separately in Phase 3 development as a stand-alone obesity treatment.