Viking Therapeutics' VK2735: Can a Dual-Acting Obesity Pill Navigate Tolerability and Competition to Win the Market?

The obesity drug market has become one of the most lucrative and fiercely contested corners of the biotech industry. With Eli Lilly's Zepbound (tirzepatide) and Novo Nordisk's Wegovy (semaglutide) dominating headlines and wallets, Viking Therapeutics' VK2735 enters the fray as a dual-acting GLP-1/GIP agonist with a unique value proposition. But can it overcome tolerability hurdles and carve out a niche in a market where efficacy and patient adherence are paramount?

Efficacy: A Promising Start, But Room for Improvement

Viking's Phase 2 VENTURE-Oral Dosing trial demonstrated that VK2735 achieved a 12.2% mean weight loss at the highest dose (120 mg) over 13 weeks—a result that, while statistically significant, lags behind the 20.2% weight loss seen with Eli Lilly's Zepbound and the 13.6% loss with Novo Nordisk's Wegovy. The drug's dual mechanism—targeting both GLP-1 and GIP receptors—suggests a theoretical advantage in appetite suppression and metabolic regulation. However, the gap in efficacy raises a critical question: Can Viking optimize dosing to close this gap without exacerbating side effects?

The trial's titration strategy—starting patients on lower doses and gradually increasing to 120 mg—was designed to mitigate gastrointestinal (GI) side effects. Yet, 38% of patients in the highest dose group discontinued due to adverse events, primarily nausea and vomiting. This is a stark contrast to Zepbound and Wegovy, which, while also associated with GI issues, have demonstrated better tolerability in long-term studies.

Tolerability: A Double-Edged Sword

Viking's CEO, Brian Lian, has emphasized that GI side effects tend to diminish with continued dosing, a pattern observed in the trial. However, the high discontinuation rate at 120 mg underscores a key challenge: balancing efficacy with patient adherence. The company's exploratory maintenance phase—transitioning patients from 90 mg to 30 mg—showed that weight loss could be sustained at lower doses. This approach could mitigate side effects while maintaining therapeutic benefits, but it remains unproven in long-term studies.

In comparison, Eli Lilly's orforglipron and Novo Nordisk's oral Wegovy have shown more favorable tolerability profiles in Phase 3 trials. For instance, orforglipron's discontinuation rate due to adverse events is projected to be below 20%, according to industry analysts. Viking's ability to refine its dosing strategy—perhaps by extending titration periods or incorporating adjunct therapies—will be critical to its commercial viability.

Dosing Optimization: A Path to Differentiation

Viking's Phase 2 results hint at a potential niche: maintenance therapy. The 30 mg maintenance dose, after an initial 90 mg phase, preserved weight loss without significant side effects. This could position VK2735 as a “second-phase” therapy for patients who achieve initial weight loss with higher-dose injectables like Zepbound or Wegovy. Such a strategy would align with growing demand for long-term weight management solutions, particularly as insurers and patients seek cost-effective options.

However, this approach hinges on Viking's injectable formulation, currently in Phase 3 trials (VANQUISH-1 and VANQUISH-2), demonstrating comparable efficacy to oral agents. If the injectable version shows improved tolerability with once-monthly dosing, it could compete directly with Wegovy and Zepbound. The company's $808 million in cash reserves as of June 2025 provides flexibility to fund these trials, but success is far from guaranteed.

Market Positioning: Oral vs. Injectable, and the M&A Angle

The obesity drug market is bifurcating into two camps: high-efficacy injectables and convenient oral alternatives. While injectables like Zepbound and Wegovy lead in weight loss outcomes, oral drugs are gaining traction for their ease of use. Viking's oral VK2735 could appeal to patients averse to injections, but its tolerability issues may limit adoption.

Analysts at William Blair note that Viking's dual formulation strategy (oral and injectable) and robust cash reserves make it an attractive acquisition target for larger pharma firms seeking to diversify their obesity portfolios. This could provide a lifeline if the company struggles to scale independently. However, the risk of M&A dilution—where Viking's stock price is driven by speculative buyout potential rather than organic growth—remains a concern for long-term investors.

Investment Outlook: High Risk, High Reward

Viking's long-term commercial potential hinges on three factors:
1. Dosing Optimization: Can the company refine its titration and maintenance strategies to reduce discontinuation rates while preserving efficacy?
2. Phase 3 Success: Will the injectable formulation demonstrate superior tolerability and efficacy compared to oral agents?
3. Market Differentiation: Can Viking carve out a niche in maintenance therapy or oral administration, despite the dominance of injectables?

For now, the data suggests a high-reward, high-risk profile. While VK2735's 12.2% weight loss is impressive for an oral agent, it falls short of the injectable leaders. The maintenance therapy approach is promising but untested at scale. Investors should monitor Viking's Phase 3 results and its ability to partner with larger firms for commercialization.

In the broader context, the obesity drug market is projected to grow to $100 billion by 2030, with oral GLP-1/GIP agonists capturing a significant share. Viking's dual-acting mechanism and dual formulation strategy position it as a potential player in this expansion, but only if it can address tolerability and demonstrate long-term efficacy.

For investors, the key takeaway is clear: Viking Therapeutics is a speculative bet with upside potential, but it requires patience and a tolerance for volatility. Those seeking a safer bet may prefer Eli Lilly or Novo Nordisk, whose established pipelines and regulatory clarity offer more predictable returns. Yet, for those willing to take a calculated risk, Viking's VK2735 could represent a compelling opportunity in the evolving obesity landscape.