CT-388 Side Effects Overview
CT-388's safety profile in Phase 1/1b trials was consistent with the GLP-1/GIP agonist class. The most common side effects are gastrointestinal in nature—however, rates were higher than some competitors, likely due to the rapid dose escalation in Phase 1 studies.[1]
Phase 1 Data Caveat
Current safety data comes from Phase 1/1b trials with limited participants and relatively fast dose escalation. Phase 2/3 trials with optimized titration protocols will provide more accurate tolerability data. GI side effects typically improve during the maintenance phase.
Side Effects at 22 mg Dose (24 Weeks)
Gastrointestinal Side Effects[2]
| Side Effect | Overall Rate | Maintenance Rate | Severity |
|---|---|---|---|
| Nausea | 83.3% | 54.2% | Mostly mild |
| Vomiting | 75.0% | 33.3% | Mostly mild |
| Diarrhea | 54.2% | 50.0% | Mild-to-moderate |
| Constipation | 58.3% | 50.0% | Mild-to-moderate |
Tolerability Indicators
- 22 mg overall discontinuation: 16.7% (4/24 patients)—but none were drug-related (reasons: food poisoning, withdrawn consent, pregnancy, drug holiday)[2]
- 8 mg discontinuation rate: 1 patient (unrelated to drug)
- Severe (Grade 3) AEs: None in maintenance period
- Overall severity: Most TEAEs mild-to-moderate
- GI AEs over time: Decreased significantly during maintenance phase
Key insight: While GI rates during rapid up-titration appear high, they decreased significantly during the maintenance period (e.g., vomiting dropped from 75% to 33.3%, nausea from 83% to 54%). This suggests tolerability improves substantially as patients reach stable dosing.
Safety in Type 2 Diabetes Patients
The T2D cohort showed notably better tolerability:[3]
- Discontinuations due to AEs: 0 (none)
- Serious adverse events: None
- GI AEs: Most frequent, majority mild and transient
- Laboratory/vital sign changes: No clinically notable changes
Excellent T2D Tolerability
The T2D cohort's 0 discontinuation rate suggests CT-388 may be well-tolerated when used with appropriate titration. The 12-week duration was also shorter than the 24-week obesity trial.
Comparison to Similar Drugs
| Drug | Nausea | Vomiting | Discontinuation |
|---|---|---|---|
| CT-388 (Phase 1b titration) | 83% | 75% | 0% drug-related |
| CT-388 (maintenance) | 54% | 33% | — |
| Tirzepatide (SURMOUNT-1) | 24-33% | 9-12% | 4-7% |
| Semaglutide (STEP 1) | 44% | 25% | 7% |
| VK2735 (Phase 2) | 43% | 18% | 13% |
Important context: CT-388's Phase 1b rates are not directly comparable to Phase 3 trial rates due to:
- Faster dose escalation in early trials
- Smaller sample sizes with greater variance
- Different patient populations
- Different trial durations
Phase 2/3 data with optimized titration will provide more accurate tolerability comparisons.
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
- Anti-nausea medication if prescribed (e.g., ondansetron)
- Know it improves: Maintenance phase rates were ~50% lower than overall rates
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
Roche's Combination Strategy
Roche is developing CT-388 in combination with Petrelintide (amylin analog from Zealand Pharma). The rationale: Petrelintide may address the GI side effects that are "the main driver of discontinuation" from GLP-1 medications. Phase 2 of the combination is planned for H1 2026.[4]
FAQs
Several factors likely contribute:
- Dose escalation speed: Phase 1 trials often use faster titration than Phase 3
- Small sample size: Higher variance with fewer patients
- Trial reporting: Phase 1 captures all events; Phase 3 often focuses on treatment-related AEs
Importantly, GI rates dropped significantly during the maintenance period, suggesting tolerability improves over time.
Based on current data, CT-388's Phase 1b GI rates appear higher than tirzepatide's Phase 3 rates. However, this comparison is limited:
- CT-388: Phase 1b data (faster titration)
- Tirzepatide: Phase 3 data (optimized titration)
CT-388's Phase 2/3 data will provide better comparisons. The signal-biased mechanism may theoretically improve tolerability—but this remains to be proven.
No. GI side effects (nausea, vomiting) are typically temporary and improve as your body adjusts. In Phase 1b trials, GI rates decreased substantially during the maintenance period:
- Nausea: 83% (titration) → 54% (maintenance)
- Vomiting: 75% (titration) → 33% (maintenance)
Most patients who tolerate the initial titration phase experience improved tolerability over time.
Sources & References
- Roche. "Roche reports positive Phase Ib results for CT-388." May 2024. https://www.roche.com/media/releases/med-cor-2024-05-16
- Chakravarthy MV, et al. "Safety, Pharmacokinetics, and Pharmacodynamics of CT-388, A Signal-Biased Dual GLP-1/GIP Receptor Agonist, Over 24 Weeks in Adults With Obesity." EASD 2024, Poster #LBA 65. EASD 2024 Poster
- Steinberg A, et al. "Glycemic Control, Weight Reduction, and Safety with CT-388." Diabetes 2025;74(Supplement_1):763-P. https://diabetesjournals.org/diabetes/article/74/Supplement_1/763-P/160045/
- FierceBiotech. "Roche unveils strategy to become 'top 3' obesity company." September 2025. https://www.fiercebiotech.com/biotech/we-have-will-roche-unveils-strategy-become-top-3-obesity-company
Last updated October 6, 2026
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