VK2735 Side Effects Overview
VK2735's safety profile in Phase 2 trials was consistent with the GLP-1/GIP agonist class. The most common side effects are gastrointestinal in nature and are typically mild-to-moderate and transient.
Phase 2 Data Only
Current safety data comes from 13-week Phase 2 trials with ~200 participants. The Phase 3 VANQUISH program (~5,750 patients, 78 weeks) will provide comprehensive long-term safety data. Rare side effects may only be detected in larger trials.
Injectable VK2735 Side Effects
Common Side Effects[1]
| Side Effect | VK2735 | Severity |
|---|---|---|
| Nausea | 43% | Mostly mild (32% mild, remainder moderate) |
| Vomiting | 18% | Mild-to-moderate |
| GI events (overall) | Common | Decreased upon repeat dosing |
Tolerability Indicators[1]
- Discontinuation rate: 13% (VK2735) vs. 14% (placebo) — no excess discontinuation due to treatment
- Serious adverse events: 1 case of dehydration (drug-related)
- Overall AE severity: 92% of adverse events were mild or moderate
- No deaths: No fatal adverse events in Phase 2
Key insight: The low discontinuation rate (balanced with placebo) suggests most patients can tolerate VK2735 despite experiencing GI side effects. The fact that GI events decreased upon repeat dosing indicates tolerability improves over time.
Oral VK2735 Side Effects
The oral tablet formulation showed a more favorable GI profile than the injectable:[2]
| Side Effect | Oral VK2735 | Notes |
|---|---|---|
| Nausea | 14-32% | Lower than injectable (43%) |
| Vomiting | 0-4% | Much lower than injectable (18%) |
| Diarrhea | 3-7% | Lower than placebo in some cohorts |
| Serious AEs | 0% | No serious adverse events reported |
- Overall severity: 99% of GI adverse events mild/moderate; 90% were mild
- Tolerability: Excellent—no serious AEs, low discontinuation
Comparison to Similar Drugs
| Drug | Nausea | Vomiting | Discontinuation |
|---|---|---|---|
| VK2735 (Phase 2) | 43% | 18% | 13% |
| Tirzepatide (SURMOUNT-1) | 24-33% | 9-12% | 4-7% |
| Semaglutide (STEP 1) | 44% | 25% | 7% |
Note: Direct comparison is difficult due to different trial durations (VK2735 13 weeks vs. 68-72 weeks for competitors). Side effects often peak during dose escalation and improve over time. Phase 3 data will provide more comparable safety profiles.
Managing Side Effects
Nausea Management
- Eat smaller, more frequent meals rather than large portions
- Avoid high-fat, greasy foods which slow digestion further
- Stay hydrated with clear fluids throughout the day
- Take anti-nausea medication if prescribed (e.g., ondansetron)
- Know it improves: GI side effects typically decrease upon repeat dosing
When to Seek Medical Attention
- Severe, persistent vomiting or diarrhea
- Signs of dehydration (dark urine, dizziness, rapid heartbeat)
- Severe abdominal pain
- Any symptoms that concern you
FAQs
No. GI side effects (nausea, vomiting) are typically temporary and improve as your body adjusts to the medication. In Phase 2 trials, GI events decreased upon repeat dosing. Most patients who tolerate the initial weeks of treatment experience minimal ongoing symptoms.
Based on Phase 2 data, VK2735 shows higher nausea rates (43%) compared to tirzepatide (24-33%). However, the discontinuation rate was similar to placebo (13% vs. 14%), suggesting overall tolerability is acceptable. The 13-week VK2735 trial vs. 72-week tirzepatide trials makes direct comparison difficult—Phase 3 will provide better comparisons.
Yes, based on Phase 2 data. The oral VK2735 tablet showed lower GI side effect rates:
- Nausea: 14-32% (oral) vs. 43% (injectable)
- Vomiting: 0-4% (oral) vs. 18% (injectable)
This may be due to different pharmacokinetics (absorption patterns) of the oral formulation. The oral version also showed no serious adverse events.
Sources & References
- Viking Therapeutics. "Positive Top-Line Results from Phase 2 VENTURE Trial." February 2024. https://ir.vikingtherapeutics.com/news-releases/news-release-details/viking-therapeutics-announces-positive-top-line-results-phase-2
- Viking Therapeutics. "Positive Top-Line Results from Phase 2 VENTURE-Oral Dosing Trial." August 2025. https://www.prnewswire.com/news-releases/viking-therapeutics-announces-positive-top-line-results-from-phase-2-venture-oral-dosing-trial-302533355.html
- Jastreboff AM, et al. "Tirzepatide Once Weekly for the Treatment of Obesity." SURMOUNT-1 Trial. N Engl J Med. 2022;387:205-216. https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
Last updated October 6, 2026
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