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Does retatrutide make you tired? Quick answer
Does retatrutide make you tired? It may be associated with tiredness in some study participants, but fatigue was not among the most common adverse events. In the 2023 Phase 2 obesity trial, 22 of 337 participants receiving retatrutide (7%) reported fatigue. By comparison, 3 of 70 participants receiving placebo (4%) reported fatigue. Rates varied across dose and escalation groups.
Retatrutide is still investigational and is not approved by Health Canada or the U.S. Food and Drug Administration. The available evidence cannot predict how any individual will respond.
This article summarizes published research for general educational purposes. It is not medical advice and does not support using a research product for self-care. Severe, persistent, or worsening fatigue should be assessed by a licensed healthcare professional.
How common is retatrutide tiredness in clinical research?
For readers asking “does retatrutide make you tired,” the pivotal evidence comes from a Phase 2 obesity trial published in the New England Journal of Medicine. It included 338 participants assigned to retatrutide and 70 assigned to placebo. The trial reported the following fatigue rates:
| Study group | Participants reporting fatigue | Rate |
|---|---|---|
| Placebo | 3 of 70 | 4% |
| Retatrutide 1 mg | 3 of 69 | 4% |
| Retatrutide 4 mg, 2 mg initial dose | 4 of 33 | 12% |
| Retatrutide 4 mg, 4 mg initial dose | 2 of 35 | 6% |
| Retatrutide 8 mg, 2 mg initial dose | 1 of 35 | 3% |
| Retatrutide 8 mg, 4 mg initial dose | 3 of 35 | 9% |
| Retatrutide 12 mg | 6 of 62 | 10% |
| All retatrutide groups | 22 of 337 | 7% |
These figures show that fatigue occurred, but they do not establish that retatrutide directly caused every report. The group sizes were also small, so differences between individual dose groups should not be treated as a precise dose-response pattern.
What is retatrutide?
Retatrutide is an investigational once-weekly molecule developed to activate three hormone receptors:
- glucose-dependent insulinotropic polypeptide (GIP) receptors;
- glucagon-like peptide-1 (GLP-1) receptors; and
- glucagon receptors.
Researchers are studying how this triple-receptor activity affects body weight, appetite, glucose regulation, and energy balance. Because clinical development is ongoing, its complete safety profile and long-term effects have not been established. Explore the Red Leaf Research Labs research library for more educational articles.
Why might retatrutide make you tired?
The clinical trial recorded adverse events but did not prove one specific mechanism for fatigue. Several factors could contribute, and more than one may occur at the same time.
Reduced food intake
Retatrutide reduced appetite in clinical studies. A substantial or rapid reduction in calorie intake can leave a person feeling low in energy, regardless of whether the compound has a direct effect on fatigue.
Nausea, vomiting, or diarrhea
Gastrointestinal events were the most commonly reported adverse events in the Phase 2 trial. These symptoms can reduce food and fluid intake and may contribute to weakness, dehydration, dizziness, or tiredness.
Changes during dose escalation
In the trial, gastrointestinal adverse events occurred mainly during dose escalation and were more frequent in higher-dose groups. That finding applies to gastrointestinal events overall; it does not prove that fatigue will follow the same timeline for every person.
Other health factors
Fatigue has many possible causes, including inadequate sleep, stress, infection, anemia, thyroid conditions, changes in blood glucose, other medications, and underlying illness. A symptom should therefore be evaluated in its full health context rather than automatically attributed to retatrutide.
Is retatrutide fatigue permanent?
The published Phase 2 study does not establish that fatigue is permanent. It also does not provide enough evidence to promise a specific duration. Because retatrutide remains investigational, conclusions about uncommon or long-term adverse effects must remain cautious.
When should tiredness be medically assessed?
A licensed healthcare professional should assess fatigue that is severe, persistent, worsening, or interfering with normal activities. Prompt medical assessment is especially important when tiredness occurs with symptoms such as fainting, confusion, chest pain, shortness of breath, persistent vomiting, severe abdominal pain, or signs of dehydration.
Do not use this article to diagnose a symptom, change a medication, or decide how to use an investigational compound.
Frequently asked questions about retatrutide and tiredness
Does retatrutide make you tired?
Yes, tiredness is possible, but it was not one of the most common effects in the published Phase 2 obesity trial. Fatigue was reported by 7% of participants in the combined retatrutide groups and 4% of those receiving placebo. This difference shows an association; it does not prove that retatrutide caused every case.
Does retatrutide make you sleepy?
Fatigue was reported in clinical research, but fatigue and sleepiness are not identical symptoms. The Phase 2 adverse-event table reported fatigue; it did not establish how often participants experienced daytime sleepiness specifically.
Is fatigue a common retatrutide side effect?
It was less common than gastrointestinal adverse events. Across the retatrutide groups in the 2023 Phase 2 obesity trial, 7% of participants reported fatigue, compared with 4% in the placebo group.
Does a higher dose cause more fatigue?
Some higher-dose groups reported fatigue more often, but the percentages did not rise consistently with every dose. The individual groups were small, so the trial does not support a simple claim that a higher dose will always cause more fatigue.
Can dehydration contribute to tiredness?
Yes. Nausea, vomiting, diarrhea, or reduced fluid intake can contribute to dehydration, which can cause fatigue and dizziness. Anyone who may be dehydrated or cannot keep fluids down should seek professional medical guidance.
Does retatrutide make you tired? Bottom line
So, does retatrutide make you tired? It may in some participants. In the main published Phase 2 obesity trial, 7% of retatrutide participants and 4% of placebo participants reported fatigue. The study does not prove a single cause or predict how long fatigue will last for an individual. Retatrutide remains investigational. A licensed healthcare professional should assess concerning symptoms.
References
- Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. 2023;389:514–526. doi:10.1056/NEJMoa2301972.
- Jastreboff AM, et al. PubMed record for the Phase 2 obesity trial. PMID: 37366315.
- Rosenstock J, Frias J, Jastreboff AM, et al. Retatrutide for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled Phase 2 trial. The Lancet. 2023;402:529–544. PMID: 37385280.
Evidence review updated July 27, 2026. This page will be revised as peer-reviewed clinical evidence develops.