Survodutide shows modest weight loss in phase 3 diabetes trial, trailing competitors

Boehringer Ingelheim and Zealand Pharma's dual agonist survodutide met its co-primary endpoints in the Phase 3 SYNCHRONIZE-2 trial, achieving up to 9.8% weight loss in patients with type 2 diabetes and obesity. However, these results trail competitors like Eli Lilly's tirzepatide and retatrutide, which achieved up to 16% and 23% weight loss in similar populations. Additionally, survodutide faced high discontinuation rates, with 18% of patients stopping treatment due to gastrointestinal side effects.

SYNCHRONIZE-2 trial results for survodutide

• ▪In the Phase 3 SYNCHRONIZE-2 trial, adults with type 2 diabetes and obesity taking 3.6 mg and 6 mg of survodutide achieved average weight loss of 8.2% and 9.8%, respectively, by week 76 under the treatment-regimen estimand.
• ▪In the SYNCHRONIZE-2 trial, mean HbA1c levels decreased by 0.9 percentage points in the 3.6 mg survodutide group and 0.8 percentage points in the 6 mg group, compared to 0.2 percentage points for placebo.
• ▪In the SYNCHRONIZE-2 trial, overall and gastrointestinal adverse events led to treatment discontinuation in 26% and 18% of patients in both survodutide groups, compared to 9% and 1.2% in the placebo group.
• ▪In the Phase 3 SYNCHRONIZE-2 trial, 79.3% of the 775 enrolled patients met the co-primary endpoint of losing at least 5% of their body weight.

Tirzepatide weight loss performance

• ▪In a 48-week Phase 2 trial, patients with obesity and type 2 diabetes taking a 15 mg dose of tirzepatide alone achieved an average weight loss of 14.8%.
• ▪In clinical trials, patients with type 2 diabetes taking tirzepatide achieved up to 15% to 16% weight loss, outperforming the 9.8% weight loss observed with survodutide.

Retatrutide clinical trial results

• ▪In an 80-week trial published in The Lancet, retatrutide helped patients with type 2 diabetes lose up to 60 pounds, or about 23% of their body weight.
• ▪In an 80-week trial, retatrutide lowered average A1C levels by up to 1.6%, compared with 0.2% for placebo.
• ▪In clinical trials, patients with type 2 diabetes taking tirzepatide achieved up to 15% to 16% weight loss, outperforming the 9.8% weight loss observed with survodutide.

Eloralintide and tirzepatide combination therapy

• ▪Eli Lilly plans to advance its combination regimen of eloralintide and tirzepatide into Phase 3 clinical trials by the end of 2026.
• ▪In a 48-week Phase 2 trial, Eli Lilly's combination of eloralintide and tirzepatide led to an average weight loss of up to 23.3% in patients with obesity and type 2 diabetes.
• ▪In Eli Lilly's Phase 2 trial of the eloralintide and tirzepatide combination therapy, 10.8% to 27% of patients discontinued treatment due to side effects, depending on the dose.
• ▪In Eli Lilly's Phase 2 trial, the combination of eloralintide and tirzepatide lowered average HbA1c levels by up to 2.9%, compared to up to 2.4% for tirzepatide alone.

Debatable claims

• ▪Obesity drug trials should prioritize visceral and liver fat reduction over total weight loss
• ▪Survodutide remains a competitive obesity treatment due to its unique liver and cardiometabolic benefits