Eli Lilly says closely watched combo obesity regimen boosts weight loss in mid-stage trial

Eli Lilly on Wednesday said its experimental combination regimen resulted in greater weight loss than a high dose of its top-selling drug, tirzepatide, alone in a mid-stage trial on patients with obesity and Type 2 diabetes.

The combo therapy met the study's main goals in a population that typically struggles to lose weight. The results raise hopes that the combo regimen could serve as an alternative blockbuster treatment option for people who didn't see the results they wanted from using the current GLP-1 products on the market. Lilly said it plans to start Phase 3 trials on the regimen at the end of the year.

The combination treatment combines Lilly's experimental drug eloralintide, which targets amylin — a hormone in the pancreas involved in appetite and satiety — with a low dose of tirzepatide, the active ingredient in its obesity injection Zepbound and its diabetes counterpart Mounjaro.

Tirzepatide targets two gut hormones, GLP-1 and GIP. Lilly believes that hitting all three pathways, including amylin, can further reduce appetite and improve weight loss — and the combo drug did just that in the 48-week Phase 2 trial.

People taking the highest dose of the combo regimen lost up to 23.3% of their weight, or around 54 pounds, on average. That treatment combined 9 milligrams of the amylin drug and 15 milligrams of tirzepatide.

Meanwhile, patients taking only a 15-milligram dose of tirzepatide saw 14.8% weight loss, or 34.4 pounds, on average. Those who took eloralintide alone lost up to 12.3% of their weight, or 28.6 pounds, on average.

"Patients may not get what they need from a drug like tirzepatide," Ken Custer, president of Lilly Cardiometabolic Health, said in an interview. "They may not get what they need from a drug like a eloralintide on its own. The ability to combine them together and provide even greater weight loss — that's definitely one obvious" benefit of the new regimen.

The combo treatment also lowered a key measure of blood sugar levels — A1C — by up to 2.9% on average. Higher-dose tirzepatide reduced A1C by up to 2.4% on average, while the amylin drug lowered it by up to 1.4% on average.

Lilly may face more questions from investors and the medical community about how well patients tolerate and stay on the highly effective combination therapy.

More patients on the combo regimen — 10.8% to 27%, depending on the dose — discontinued treatment due to side effects, compared with the 2.9% of people on tirzepatide alone in the trial.

Up to 10.8% of people on the amylin drug alone discontinued treatment due to side effects, compared with 16.7% with placebo.

Lilly said the side effects were more frequent in groups taking the combination regimen compared with tirzepatide or the amylin drug alone. The most common side effects of the combo therapy were gastrointestinal-related, generally mild or moderate in severity, and mainly occurred when patients increased doses in the trial.