# Retatrutide Side Effects Observed in Clinical Trials

> Retatrutide side effects from Phase 2 and Phase 3 clinical trials: nausea up to 60% (Phase 2, 12 mg), diarrhea, vomiting, constipation, heart rate increase. Documented adverse event data, cited.

## Common Retatrutide Side Effects

Retatrutide side effects in Phase 2 and Phase 3 clinical trials are predominantly gastrointestinal, dose-dependent, and most prominent during the dose-escalation period.

Phase 2 obesity trial data (n=338, up to 48 weeks, 12 mg maximum dose) [3]:

| Adverse event | Phase 2, 12 mg | Phase 3, 12 mg | Severity |
|--------------|---------------|---------------|---------|
| Nausea | ~60% | 42.4% | Predominantly mild to moderate |
| Diarrhea | 15–33% | 32.0% | Dose-dependent |
| Vomiting | 21–26% | 25.3% | Higher-dose arms |
| Constipation | 11–16% | 26.1% | Dose-dependent |
| Decreased appetite | ~14% | N/R | As an adverse event |
| Injection-site reactions | ~8% | N/R | Across all active arms |

Phase 3 TRIUMPH-1 data (n=2,339, 80 weeks) [23]: nausea 42.4%, diarrhea 32.0%, constipation 26.1%, vomiting 25.3%.

No deaths were reported in either Phase 2 trial. No pancreatitis or thyroid C-cell tumor signals were identified in Phase 3 data to date [23].

## Serious Risks Studied in Retatrutide Trials

**Heart rate elevation:** Up to 6.7 beats per minute in Phase 2 obesity trial data. The increase peaked at approximately week 24 and declined thereafter. Glucagon-receptor-mediated chronotropic effect. Systolic blood pressure decreased in Phase 2 data [16].

**Atrial fibrillation:** One participant in the Phase 2 T2D cohort (8 mg arm, n=26) experienced atrial fibrillation (3.85%) [16]. Single event in a small cohort.

**Class-effect signals monitored:**
- Pancreatitis: no signal identified in Phase 3 data [23]
- Thyroid C-cell risk: no signal identified in Phase 3 data [23]
- GCGR in T2D: theoretical concern for hepatic glycogenolysis in fasting states; net glycemic effect is favorable due to GLP-1R/GIPR co-activation [4]

The cardiovascular outcomes trial TRIUMPH-OUTCOMES (NCT06383390) is the registrational safety study. Long-term cardiovascular outcomes data from the full TRIUMPH program are pending.

## What Happens When You Stop Retatrutide?

No Retatrutide-specific long-term discontinuation study has been published as of mid-2026. Class-effect pattern from analogous compounds [19]:

- Semaglutide STEP 4: 6.9% weight regain after switching to placebo versus continued −7.9% loss
- Tirzepatide SURMOUNT-4: 14.0% regain after switching versus continued −5.5% loss

Most lost weight recovered within 12 months of stopping in the analogous-compound withdrawal studies. Mechanism: recovery of orexigenic signaling once appetite suppression is removed [19].

## Weight Regain After Discontinuing Retatrutide

Class-effect data from GLP/GIP-class agonist withdrawal studies: majority of lost weight recovered within 12 months [19]. Retatrutide-specific discontinuation data expected from longer-term TRIUMPH follow-up.

One notable finding in preclinical data: anti-tumor immune reprogramming persisted after drug withdrawal despite weight regain in the murine oncology model [8]. Whether any metabolic changes show similar durability in humans is not known from published data.

## References

[3] Jastreboff AM, et al. Triple–Hormone-Receptor Agonist Retatrutide — adverse events. N Engl J Med. 2023;389:514-526.
[4] Rosenstock J, et al. Retatrutide for T2D. Lancet. 2023.
[8] Marathe SJ, et al. Incretin triple agonist retatrutide alleviates obesity-associated cancer progression. NPJ Metab Health Dis. 2025.
[16] Doggrell SA. Retatrutide showing promise in obesity. Expert Opin Investig Drugs. 2023.
[19] Quarenghi M, et al. Weight Regain After Liraglutide, Semaglutide or Tirzepatide Interruption. J Clin Med. 2025.
[23] The Pharmaceutical Journal. Phase III retatrutide study demonstrates 30% weight loss. 2026.

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Plain-language summaries of the Phase 2 and Phase 3 Retatrutide trial record — independent, cited, and not a clinical service.