Boehringer, Zealand obesity drug face tolerability questions after Phase 3 success
Boehringer Ingelheim’s survodutide delivered average weight loss of up to 13.1% in a Phase 3 trial involving people with overweight or obesity and type 2 diabetes, but gastrointestinal side effects caused 18% of patients receiving the drug to stop treatment.
Why it matters: The results strengthen the evidence for the Zealand Pharma-originated drug in a population where weight loss is typically harder to achieve. However, its efficacy faces strong competition from existing treatments, while the discontinuation rate raises questions about how many patients could sustain treatment.
Zoom in: The 755-participant SYNCHRONIZE-2 trial tested weekly survodutide injections at doses of 3.6 mg or 6 mg against placebo over 76 weeks.
- Average weight loss reached up to 13.1%, compared with 3.1% on placebo.
- Up to 79.3% of survodutide recipients lost at least 5% of their body weight, versus 32.7% on placebo.
- HbA1c, a measure of longer-term blood sugar control, fell by up to 1.21 percentage points from a baseline of 7.4%, compared with 0.03 points on placebo.
The trial met both primary endpoints under two statistical approaches.
How it works: Survodutide activates GLP-1 and glucagon receptors. Its GLP-1 activity helps reduce appetite and improve blood sugar control, while glucagon activity is intended to contribute to weight loss and liver-fat reduction. Because glucagon normally raises blood sugar, the improvement in HbA1c provides evidence that the combined mechanism can deliver weight loss alongside glucose control in people with diabetes.
The competition: The obesity market is a tough nut to crack. Novo’s semaglutide 2.4 mg produced 10.6% average weight loss in STEP 2, while Lilly’s tirzepatide delivered 13.4% at 10 mg and 15.7% at 15 mg in SURMOUNT-2. Both trials enrolled people with overweight or obesity and type 2 diabetes.
- That places survodutide numerically between semaglutide 2.4 mg and tirzepatide’s highest dose, although differences between the trials prevent final conclusions about superiority.
The bar is rising: A day earlier, Lilly reported 23.3% average weight loss at 48 weeks with its experimental eloralintide–tirzepatide combination in people with overweight or obesity and type 2 diabetes. The Phase 2b result adds competitive pressure on survodutide, although up to 27% discontinued the combination because of adverse events. Lilly plans to begin Phase 3 trials in the fourth quarter.
The catch: Similarly to Lilly’s recent result, Boehringer’s trial reported that gastrointestinal adverse events caused 18% of survodutide recipients to discontinue treatment, versus 1.2% on placebo. In Lilly’s SURMOUNT-2 with tirzepatide alone, gastrointestinal events led fewer than 5% of recipients to stop treatment.
- Boehringer said discontinuations generally occurred during dose escalation, when the protocol allowed limited flexibility to manage side effects. Current and upcoming trials permit more flexible dosing, but whether that improves treatment persistence remains to be demonstrated.
What’s next: Boehringer expects cardiovascular outcomes results later this year and has launched a separate Phase 3 trial focused on blood sugar control. Its broader program also targets metabolic dysfunction-associated steatohepatitis (MASH). Those studies could help establish survodutide’s clinical value beyond weight loss, while more flexible dosing will need to address its tolerability challenge.
Yes, but: Investors aren’t so optimistic. Zealand Pharma shares fell about 10% in early trading Thursday following the readout.
