Next-Gen Incretin Challengers: Viking's Oral VK2735 and Roche's CT-388 Phase 2 Results

The competitive landscape for weight loss therapeutics is rapidly expanding beyond Eli Lilly and Novo Nordisk. Clinical-stage challengers are presenting highly competitive Phase 2 data, demonstrating best-in-class potential in weight loss efficacy, tolerability, and dosing convenience.

Viking Therapeutics’ Oral VK2735: Compelling 13-Week Weight Loss

On May 12, 2026, Viking Therapeutics (NASDAQ: VKTX) presented highly anticipated data from its 13-week Phase 2 VENTURE-Oral study of VK2735 at the European Congress on Obesity (ECO) in Istanbul, Turkey. VK2735 is a dual GLP-1/GIP receptor agonist being developed in both oral and subcutaneous formulations.

• Efficacy: Patients receiving the highest daily oral dose (120 mg) of VK2735 achieved a mean weight loss of 12.2% (26.6 lbs) from baseline at 13 weeks, translating to a placebo-adjusted weight loss of 10.9% (p<0.0001).
• Progressive Trajectory: Weight loss was progressive and occurred early (beginning at Week 1 for doses >15 mg) with no plateau observed through Week 13, suggesting that longer-duration treatment will yield further weight reduction.
• Tolerability: The oral formulation demonstrated an encouraging tolerability profile. 98% of treatment-emergent adverse events (TEAEs) were categorized as mild or moderate, and gastrointestinal events diminished over time.
• Phase 3 Plans: Viking plans to initiate Phase 3 registration trials for the oral tablet later in 2026. Concurrently, its weekly subcutaneous formulation is in the ongoing Phase 3 VANQUISH registration program (VANQUISH-1 and VANQUISH-2).

Roche’s CT-388: 22.5% Weight Loss at 48 Weeks

On January 26, 2026, Roche announced positive topline results from its Phase 2 trial of CT-388, a once-weekly subcutaneous dual GLP-1/GIP receptor agonist acquired through its purchase of Carmot Therapeutics.

• Efficacy: At the highest dose tested (24 mg), CT-388 achieved a statistically significant placebo-adjusted weight loss of 22.5% (efficacy estimand) at 48 weeks, without reaching a weight loss plateau.
• Resolution of Obesity: 54% of participants on the 24 mg dose achieved resolution of obesity (defined as a BMI <30 kg/m²), compared to just 13% in the placebo group. At week 48, 26.1% of treated participants achieved a massive weight loss of ≥30%.
• Biased Signaling Mechanism: CT-388 is designed to potently activate both GLP-1 and GIP receptors with minimal to no β-arrestin recruitment. This biased signaling minimizes receptor internalization and desensitization, leading to prolonged pharmacological activity.
• Phase 3 Transition: Roche is designated CT-388 as a fast-track asset and is initiating its Phase 3 clinical trial program (Enith1 and Enith2) in Q1 2026.

Verbatim Evidence

"Participants receiving once-daily oral VK2735 demonstrated statistically significant, dose-dependent weight loss from baseline of up to 12.2% (26.6 lbs) at 13 weeks across all dose cohorts. Compared with placebo, doses >15 mg demonstrated dose-dependent and progressive weight loss starting early in treatment and continuing through the 13-week treatment window, with no plateau. Up to 97% of VK2735-treated participants achieved ≥5% weight loss, and up to 80% achieved ≥10%... We are excited to move oral VK2735 into Phase 3 development as we believe it has the potential to become the first oral dual agonist of the GLP-1 and GIP receptors to reach the market." — Viking Therapeutics Press Release: May 12, 2026

"A once-weekly subcutaneous injection of CT-388 achieved a statistically significant placebo-adjusted weight loss of 22.5% (p < 0.001) at 48 weeks at the highest dose tested (24 mg), without reaching a weight loss plateau... 54% of participants on the 24 mg dose achieved resolution of obesity (BMI <30 kg/m2) vs. 13% in the placebo group... The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development programme as we advance to Phase III trials." — Roche Press Release: January 26, 2026

Investor Implications

• Viking's Differentiated Oral-to-Injectable Strategy: Viking's ability to offer both a highly effective oral tablet and a matching subcutaneous injection using the same active therapeutic agent (VK2735) represents a unique clinical and commercial advantage. This allows patients to seamlessly transition from intensive injectable weight loss to oral maintenance therapy, positioning Viking as a premium acquisition target or standalone contender.
• Roche Emerges as a Top-Tier Competitor: With CT-388 demonstrating 22.5% weight loss at 48 weeks (rivaling Eli Lilly's Zepbound and Novo's Wegovy), Roche has established itself as a formidable third player in the obesity market. Its biased-signaling design could translate to longer-lasting efficacy and fewer desensitization issues over multi-year treatment courses.