How long do you have to take retatrutide? A Look at Long-Term Treatment

October 9, 2025 •

4 min read

In a phase 2 clinical trial, participants taking retatrutide for 48 weeks achieved an average weight loss of up to 24.2% [1.6.2, 1.3.6]. This raises a critical question for potential users: for those who see such results, how long do you have to take retatrutide?

Quick Summary

Retatrutide, an investigational medication, is intended for long-term use to manage chronic conditions like obesity. Treatment duration is indefinite, as stopping the drug often leads to weight regain.

Key Points

Long-Term Treatment: Retatrutide is intended for long-term, potentially lifelong, use to manage chronic conditions like obesity, not as a short-term cure [1.9.5].
Chronic Disease Management: Obesity is a chronic disease, and stopping medication often leads to weight regain as the body's biology counteracts the loss [1.9.2].
Clinical Trial Duration: Ongoing clinical trials for retatrutide are designed to last for extended periods, from 77 weeks to 5 years, highlighting its long-term application [1.2.2, 1.3.3].
Triple-Agonist Mechanism: Its unique mechanism targets three metabolic hormones (GLP-1, GIP, GCG) to control appetite and increase metabolism, but this effect is only present while taking the drug [1.6.2].
Weight Regain Upon Stopping: Studies on similar medications show that patients can regain about two-thirds of their lost weight within a year of discontinuing treatment [1.9.3, 1.9.5].
Investigational Status: As of late 2025, retatrutide is still in phase 3 clinical trials and not yet FDA-approved for general use [1.6.1, 1.8.1].
Side Effects: The most common side effects are gastrointestinal (nausea, diarrhea) and tend to be mild to moderate; long-term safety is still being evaluated [1.5.4, 1.6.2].

Understanding Retatrutide and Its Purpose

Retatrutide is an investigational weekly injectable medication developed by Eli Lilly that is showing significant promise for managing obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) [1.4.6, 1.5.2]. As of late 2025, it is still in phase 3 clinical trials and has not yet been approved by the FDA [1.8.1, 1.6.1]. Unlike previous medications, retatrutide is a triple-receptor agonist, targeting three key metabolic hormones: glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon (GCG) [1.6.2, 1.6.3]. This unique triple-action mechanism works synergistically to reduce appetite, increase energy expenditure, and improve metabolic efficiency, leading to substantial weight loss [1.6.2, 1.6.4, 1.6.5].

The Chronic Nature of Obesity Demands Long-Term Treatment

To answer the question of treatment duration, it's essential to understand the conditions retatrutide aims to treat. Obesity is classified as a chronic, relapsing disease, not a temporary condition that can be 'cured' [1.9.2]. The body has powerful biological mechanisms that defend its highest-ever weight [1.9.2]. When a person loses weight, hormonal changes often increase appetite and slow metabolism, making weight regain a common outcome [1.9.3].

Medications like retatrutide work by counteracting these biological responses. They help regulate appetite and metabolism, but only while the medication is active in the body [1.4.1]. Studies on similar GLP-1 medications show that when patients stop treatment, they often regain a significant portion of the weight they lost, typically around two-thirds within a year [1.9.3, 1.9.5]. Therefore, for sustained benefits, retatrutide is intended to be a long-term, and potentially lifelong, treatment [1.9.5].

Evidence from Clinical Trials

While long-term data is still emerging, the structure of retatrutide's clinical trials points towards extended use. Various phase 3 trials are designed to last for significant periods:

TRIUMPH-AIM 1 (Obesity/Overweight): This study lasts about 89 weeks [1.2.2, 1.3.5].
TRIUMPH-3 (Knee Osteoarthritis): This trial has a duration of about 77 weeks [1.3.2].
TRIUMPH-6 (Maintenance of Weight Reduction): This study involves an 80-week lead-in phase followed by a 36-week randomized phase, totaling about 125 weeks (nearly 2.5 years) to assess how well the drug maintains weight loss [1.2.1, 1.2.5, 1.8.3].
TRIUMPH-CVOT (Cardiovascular Outcomes): This study is designed to last for approximately 5 years to evaluate long-term heart and kidney benefits [1.3.3].

The extended duration of these trials underscores the medical community's understanding that effective management of obesity and related conditions requires continuous, long-term pharmacological support.

What Happens if You Stop Taking Retatrutide?

Stopping retatrutide will not cause withdrawal symptoms, but the therapeutic effects will cease [1.4.1]. The hormonal regulation of appetite and metabolism will revert to its pre-treatment state. This typically leads to:

Increased Appetite: You will likely feel hungrier and experience more food cravings [1.9.3].
Weight Regain: Without the medication's effects, most individuals regain a substantial amount of the lost weight [1.9.4]. Studies on similar drugs show this regain can be rapid [1.9.3].
Metabolic Changes: Improvements in blood sugar control and other metabolic markers may reverse [1.9.5].

Because of these effects, any decision to stop the medication should be made in consultation with a healthcare provider who can help create a plan to mitigate weight regain through intensive lifestyle management [1.9.1].

Comparison with Other GLP-1 Medications

The expectation of long-term use for retatrutide is consistent with other medications in its class, such as semaglutide and tirzepatide.


Feature	Semaglutide (Wegovy/Ozempic)	Tirzepatide (Zepbound/Mounjaro)	Retatrutide (Investigational)
Mechanism	GLP-1 Agonist [1.7.1]	Dual GLP-1/GIP Agonist [1.7.1]	Triple GLP-1/GIP/GCG Agonist [1.7.1]
Administration	Weekly Injection [1.7.1]	Weekly Injection [1.7.1]	Weekly Injection [1.6.1]
Average Weight Loss	~15% of body weight [1.7.3]	~15-22% of body weight [1.7.1]	Up to 24%+ of body weight [1.7.1, 1.3.6]
Treatment Approach	Long-term for chronic disease [1.9.5]	Long-term for chronic disease [1.9.5]	Expected to be long-term for chronic disease [1.5.6]

All these medications are designed for continuous use to manage the chronic nature of obesity and diabetes. Retatrutide's potential for greater efficacy does not change this fundamental treatment principle; it reinforces the drug's role as a powerful tool for long-term disease management.

Potential Long-Term Side Effects

As retatrutide is still under investigation, its full long-term side effect profile is not yet completely known [1.5.4]. Current data from trials lasting up to 48 weeks show that the most common side effects are gastrointestinal, including nausea, diarrhea, and vomiting, which are typically mild to moderate and often decrease over time [1.6.2, 1.6.6]. Other observed, though less common, effects in trials include temporary increases in liver enzymes and a single reported case of pancreatitis [1.5.4]. Ongoing long-term studies, like the 5-year cardiovascular outcomes trial, are essential for establishing a comprehensive safety profile for extended use [1.3.3, 1.5.6]. It is also important to obtain the medication from reputable sources once approved, as the FDA has warned against counterfeit versions that can be dangerous [1.5.3].

Conclusion

Based on the chronic nature of obesity, the mechanism of action of incretin mimetics, and the structure of its ongoing clinical trials, the answer to 'How long do you have to take retatrutide?' is indefinitely. Retatrutide is not a short-term fix but a long-term management tool. Just as a person with high blood pressure takes medication continuously to control it, a person with obesity will likely need to take retatrutide continuously to maintain weight loss and the associated health benefits [1.9.2]. Discontinuing the medication will, in most cases, lead to the return of lost weight. The final guidance will depend on the FDA's approval and labeling, but all current evidence points toward a long-term treatment strategy.

For more information on ongoing trials, you can visit the official registry. [Link: https://clinicaltrials.gov/]

Frequently Asked Questions

For the management of chronic conditions like obesity, retatrutide is intended for long-term, and potentially lifelong, use to maintain its benefits. Stopping the drug typically leads to weight regain [1.9.5, 1.9.2].

If you stop taking retatrutide, the medication's effects on appetite suppression and metabolism will wear off. This commonly leads to an increased appetite and the regaining of weight that was lost [1.4.1, 1.9.3].

Retatrutide is currently in phase 3 clinical trials. Eli Lilly expects to release data in 2025, but the timeline for potential FDA approval and availability is likely 2026 or later, depending on trial outcomes and regulatory review [1.8.1, 1.6.1].

Retatrutide is a triple-agonist (GLP-1, GIP, GCG), while Ozempic (semaglutide) is a single GLP-1 agonist and Mounjaro (tirzepatide) is a dual GLP-1/GIP agonist. This triple action may lead to greater weight loss and metabolic effects [1.7.1, 1.7.2].

Based on clinical trial data, the most common side effects are gastrointestinal issues such as nausea, diarrhea, and vomiting. These are generally reported as mild to moderate in severity and often occur during the initial dose-escalation period [1.6.1, 1.6.2].

No, as of late 2025, retatrutide is an investigational drug and not yet approved by the FDA. It is only available to participants in clinical trials. The FDA warns against purchasing medications from unapproved sources [1.5.3, 1.6.1].

In a phase 2 study, participants taking the highest dose of retatrutide for 48 weeks achieved an average weight loss of 24.2% of their initial body weight [1.3.6]. Results from ongoing phase 3 trials will provide more data.