Viking's Oral Dual Incretin Agonist VK2735 Produces Up to 12% Weight Loss at 13 Weeks in Midstage Trial

VK2735, an investigational oral dual glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonist, achieved primary and secondary endpoints in the phase 2 VENTURE-Oral Dosing trial, according to an August 19 announcement from Viking Therapeutics, with weight loss among VK2735-treated participants significantly surpassing that of participants in the placebo arm after 13 weeks of once-daily treatment.¹

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Viking reported that VK2735 reduced mean body weight across doses of 30–120 mg by 7.0% to 12.2% from baseline vs reduction of just 1.3% with placebo (P <.001 for all comparisons of 30 mg or greater), satisfying the study's primary endpoint. At the highest dose of 120 mg, the placebo-adjusted mean weight loss reached 10.9%. The absolute mean reductions in body weight observed in participants in the VK2735 arm ranged from −7.1 kg to −12.1 kg, Viking said, compared with −1.3 kg for placebo. Notably, body weight reductions were progressive across the doses studied with no plateau observed during the 13-week period, an indication that weight loss could continue with ongoing treatment.¹

The midstage VENTURE-Oral Dosing trial also met key secondary endpoints: Nearly all (up to 97%) of VK2735-treated participants achieved weight loss of 5% or greater while just 10% of those who took placebo met that mark. Up to 80% taking the study drug reached weight loos of 10% or more compared with s 5% taking placebo (P <.001 at doses of 60 mg or greater). By the first week of the study, researchers recorded statistically significant differences in weight loss from baseline and from placebo for VK2735 doses higher than 15 mg and those differences persisted throughout treatment, according to the statement.¹

Potential for Low-Dose Maintenance Dosing

Viking pursued an exploratory maintenance protocol during the study to evaluate rapid titration of the dual incretin agonist to 90 mg followed by down-titration to 30 mg. Results showed body weight reduction of 8.1% at week 6 on 90 mg that was then maintained through week 13 on 30 mg. The final placebo-adjusted mean reduction was calculated at 7.9% (P <.001). These findings augur well for a low-dose maintenance regimen of the novel oral formulation following treatment induction with a higher dose, Viking said.

"As in prior studies [of VK2735] we observed a clear dose response and impressive weight loss across the 13-week treatment period. The progressive nature of the weight loss curves suggests the potential for further improvement with longer dosing periods." Viking CEO Brian Lian, PhD, said in the company statement. "The experimental maintenance arm of this study provides an encouraging signal that supports our belief that transitioning patients from higher doses, injectable or oral, to low oral doses represents a promising approach to weight maintenance therapy."¹

VK2735 is a dual agonist of the GLP-1/GIP receptors being evaluated in both oral and subcutaneous formulations for obesity and other metabolic disorders, according to Viking. It is believed that co-activation of the GIP receptor may enhance the therapeutic effects of GLP-1 receptor agonism. Tirzepatide, another dual GLP-1/GIP agonist, is already approved in the US for type 2 diabetes and obesity.¹

Safety findings showed gastrointestinal adverse events consistent with incretin-based therapies. Discontinuation rates were 28% with VK2735 and 18% with placebo. Among VK2735-treated patients, 98% of drug-related treatment-emergent adverse events were mild or moderate. Nausea occurred in 58% of treated participants versus 48% with placebo; 99% of nausea was mild or moderate. Vomiting was reported in 26% of VK2735 patients compared with 10% of placebo. Weekly nausea or vomiting incidence fell below 5% after week 3.¹

The randomized, double-blind, placebo-controlled multicenter trial enrolled 280 adults with obesity (BMI ≥30 kg/m²)or overweight (BMI ≥27 kg/m²) plus at least one comorbidity. Participants were randomly assigned evenly across the 6 dosing cohorts or placebo.¹

"We are excited to report the top-line phase 2 study results for the once-daily oral tablet of VK2735," Lian said. The company is evaluating a subcutaneous formulation of VK2735 in a phase 3 obesity program that includes 2 pivotal phase 3 clinical trials (VANQUISH-1 and VANQUISH-2).²

References

1. Viking Therapeutics announces positive top-line results from phase 2 VENTURE-Oral dosing trial of VK2735 tablet formulation in patients with obesity. News release. Viking Therapeutics. August 19, 2025. Accessed August 19, 2025. https://ir.vikingtherapeutics.com/2025-08-19-Viking-Therapeutics-Announces-Positive-Top-Line-Results-from-Phase-2-VENTURE-Oral-Dosing-Trial-of-VK2735-Tablet-Formulation-in-Patients-with-Obesity

2. Viking Therapeutics announces initiation of phase 3 obesity clinical program with GLP-1/GIP agonist VK273. News release. Viking Therapeutics. June 25, 2-25. Accessed August 19, 2025. https://ir.vikingtherapeutics.com/2025-06-25-Viking-Therapeutics-Announces-Initiation-of-Phase-3-Obesity-Clinical-Program-with-GLP-1-GIP-Agonist-VK2735