Eli Lilly’s phase 2b trial reveals that combining the amylin receptor agonist eloralintide with tirzepatide results in greater weight loss and blood sugar control in adults with type 2 diabetes and obesity, prompting plans for phase 3 development.
Eli Lilly said an experimental amylin receptor agonist, eloralintide, helped adults with type 2 diabetes and obesity lose more weight when it was used alongside tirzepatide than when tirzepatide was used on its own, according to phase 2b findings presented at the European Association for the Study of Diabetes meeting in Milan. In the highest-dose combination arm, patients lost 23.3% of their body weight over 48 weeks, compared with 14.8% for tirzepatide 15 mg alone. Lilly’s data also showed that the treatment lowered blood sugar further, adding to the case for combination approaches in a condition that is often difficult to manage with one drug alone.
The study enrolled 367 adults in the US and Argentina with overweight or obesity and type 2 diabetes and compared multiple dose pairings of eloralintide and tirzepatide against tirzepatide alone, eloralintide alone and placebo. According to Lilly’s announcement, all of the combination groups reduced HbA1c by at least 2.2 percentage points, while the best-performing regimen cut it by 2.9 percentage points. Nearly all patients in the combination arms reached an HbA1c below 7%, and a substantial share moved into the non-diabetes range of below 5.7%.
The results also point to the growing appeal of combining drugs that act through different biological pathways. Tirzepatide is already known as a dual GLP-1 and GIP agonist, while amylin works through a separate mechanism tied to appetite and food intake. Rachel Batterham, who leads medical innovation and external engagement at Lilly, told Healio that this difference in mechanism is why the company sees an additive effect on both weight and glycaemic control. Lilly plans to move to a phase 3 programme and said it intends to test a co-formulated version of the two medicines in a single injection, rather than the separate injections used in the phase 2b study.
Safety remains the main question. Gastrointestinal side effects were the most common, including nausea, diarrhoea, constipation, fatigue and reduced appetite. Healio reported that adverse events were generally similar across study groups, although nausea, fatigue and vomiting were more frequent in the highest-dose combination arm than with tirzepatide alone. Medical Daily, citing the company’s release, said discontinuations from side effects were higher with the combination than with tirzepatide monotherapy, underscoring the trade-off between greater efficacy and tolerability that will need to be tested more fully in later-stage trials.
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