Lilly’s experimental drug combination outperforms tirzepatide in mid-stage obesity trial, but tolerability questions emerge

Eli Lilly’s novel combination of amylin drug eloralintide with tirzepatide shows significant weight loss and improved blood sugar control in phase 2 trials, posing a challenge to competitors despite concerns over side effects.

Eli Lilly has once again widened its lead in the increasingly crowded market for obesity medicines, after reporting mid-stage data suggesting that its experimental amylin drug eloralintide may work especially well when paired with tirzepatide, the active ingredient in Zepbound and Mounjaro.

According to Lilly, the combination, known as EloraTZP, helped adults with obesity and type 2 diabetes lose an average of 23.3% of their body weight over 48 weeks at the highest dose, a result presented at the European Association for the Study of Diabetes meeting in Milan. In a population that is typically harder to treat than people with obesity alone, the company said the result translated into about 54.1 pounds of weight loss, compared with 34.4 pounds, or 14.8%, for tirzepatide alone.

The results matter because the field has been moving quickly from simple GLP-1 drugs to more complex combinations that aim to deepen weight loss without creating intolerable side effects. BioCentury reported that the latest findings put Lilly ahead not only of Novo Nordisk’s closely watched CagriSema programme, but also of Lilly’s own triple-agonist candidate retatrutide, at least on the basis of the newly disclosed data in this patient group.

Lilly also said the combination appeared to improve blood sugar control more than tirzepatide alone, with A1C falling by as much as 2.9% at 48 weeks. That finding is particularly relevant in type 2 diabetes, where weight reduction and glucose control are both important treatment goals. By contrast, Lilly’s own earlier Phase 3 data on tirzepatide in people with obesity and type 2 diabetes showed mean weight loss of 13.4% to 15.7% depending on dose, underscoring how much additional effect the company hopes amylin agonism can deliver.

There is, however, an important caution. Medical Daily reported that up to 27% of participants on the combination discontinued treatment because of side effects, compared with 2.9% on tirzepatide alone. That raises a familiar question for the obesity drug race: whether more weight loss can be translated into a regimen patients are willing and able to stay on for the long term. Lilly’s own announcement of the broader eloralintide programme in people without diabetes had already suggested strong efficacy, with weight loss ranging from 9.5% to 20.1% in a separate Phase 2 study, but the latest data indicate that tolerability may become the key issue if the company moves the combination forward.