Two trials presented at the European Association for the Study of Diabetes annual meeting illustrate the promise and the pitfalls of newer combination therapies for type 2 diabetes and obesity. In a phase IIb study, the investigational combination of eloralintide and tirzepatide produced striking weight loss: participants on the highest dose lost 23.3% of their body weight over 48 weeks, compared with 14.8% for tirzepatide alone. That result surpasses typical weight loss seen with tirzepatide in people without diabetes, and a quarter of those on the highest combination dose lost at least 30% of their body weight, a benchmark comparable to metabolic surgery.
By contrast, the phase III SYNCHRONIZE-2 trial of survodutide, a dual GIP/GLP-1 agonist, showed more modest effects. Participants taking 6 mg lost an average of 9.8% of their body weight by week 76, versus 3.9% with placebo. The authors noted this magnitude is still associated with cardiovascular benefits, but it falls short of the 13% weight loss seen in a prior survodutide trial that excluded people with diabetes, and it is lower than results reported for semaglutide, tirzepatide, and retatrutide in similar populations.
Both studies reported high rates of adverse events and discontinuations. In the eloralintide-tirzepatide trial, 84% of the highest-dose group experienced treatment-emergent adverse events, and 27% stopped treatment because of them, compared with 2.9% for tirzepatide alone. In the survodutide trial, gastrointestinal events were common, and 26% of participants in both treatment groups discontinued due to adverse events, versus 9% with placebo. One expert suggested survodutide's high dropout rate may be tied to its prolonged dose-escalation schedule, which was reportedly requested by the FDA.
The two reports agree that these agents can meaningfully improve weight and glycemic control, but they differ in magnitude: the eloralintide-tirzepatide combination appears far more potent, while survodutide's effects are more modest. Both, however, highlight a shared challenge: tolerability remains the key limitation that will need to be addressed as these therapies move forward. The developers of both drugs say they are planning further trials, with eloralintide-tirzepatide advancing to phase III and survodutide's developers exploring more flexible dosing strategies.