Healthcare provider explaining what retatrutide is to patient

What Is Retatrutide?

Written on November 20, 2023 by Amy Harris, MPH, RN. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

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If you are considering whether to try one of the newer weight management medications, you are not alone. Glucagon-like Peptide-1 (GLP-1) agonists are the latest weight management medications. The GLP-1 market size is estimated at USD 11.87 billion in 2023 and is expected to reach USD 12.55 billion by 2028.[1] Demand for these newest drugs is surging, leading to shortages and the development of additional medications in this class. Your healthcare dollars are precious. Before deciding which medication to spend your dollars on, you should learn more about one of the newest weight management medications, retatrutide.

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What Is Retatrutide?

Retatrutide is an experimental medication for treating type 2 diabetes and obesity. It is an injection administered once weekly, just like Ozempic® and Wegovy®.

Is Retatrutide FDA-Approved for Weight Loss Management?

No, it is not. It is currently in Stage 3 of clinical trials, so your healthcare provider can not yet prescribe it.[2] Although not yet approved, its developer, Eli Lilly, claims it will treat obesity, diabetes, and fatty liver disease by helping patients lose weight, reduce blood sugar levels, and lower fatty acids in their liver.[3]

If It Is a Diabetes Drug, How Can Retatrutide Help with Weight Loss?

It is not unusual for diabetes medications to be prescribed for weight loss. Retatrutide is a gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptor agonist. Whereas Ozempic® has a single mechanism of action as a GLP-1 agonist, retatrutide has three. That means retatrutide may be even more effective than Mounjaro®, which only has two mechanisms of action: a GLP-1 agonist and a glucose-dependent insulinotropic polypeptide (GIP). Retatrutide’s “triple attack” on hunger works by [4,5]:

  1. Slowing the emptying of your stomach after eating to help you feel fuller longer
  2. Stabilizing post-eating blood sugar spikes, stimulating the release of insulin, and storing away more sugar as glucose
  3. Impacting glucagon hormone levels to suppress appetite and help you burn more energy

Because other GLP-1 receptor agonists have the same side effect of causing weight loss, healthcare providers now prescribe them for weight management, even in people who don’t have type 2 diabetes. Some of the other GLP-1 agonists used in this way that you may have heard of are Wegovy®, Ozempic®, Rybelsus®, Saxenda®, and Mounjaro®.

Could Retatrutide Be More Effective for Weight Loss Than Other Weight-Loss Drugs?

It might be, but it is too soon to tell. During the clinical trial phase, people with obesity who took the highest dose of retatrutide lost an average of 17.5 percent of their starting weight after nearly six months — halfway through. By week 48 (1 year), subjects lost more than 24 percent — an average of 58 lbs or roughly one-quarter of their starting weight.[4] This loss is a more significant initial weight loss than with Wegovy® or Ozempic®.[6,7]

In addition, nearly all 338 adult participants who took lower doses of retatrutide saw a 5 percent to 15 percent weight reduction.[4] This amount of weight change (a 10-20 pound weight loss in someone who weighs 200 pounds, for example) is significant because other studies show that losing 5-10 percent of one's weight over six months may lead to improvements in blood pressure, cholesterol levels, prediabetes or diabetes, and metabolic syndrome.[8]

Given the cost and risk of possible side effects, many people want to know, “What is the most effective weight loss drug?” Until phase 3 clinical trials finish, we won’t know if the answer to that question is retatrutide. Everlywell offers the comprehensive WeightCare+ Program to connect you with expert nurse practitioners via telehealth to find the best weight management option, including weight loss prescriptions online, if they are right for you.

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What Conditions Could Retatrutide Treat?

Drug developers and healthcare providers hope that retatrutide will be a novel, highly effective treatment for [2,3]:

  1. Type 2 diabetes
  2. Obesity
  3. Fatty Liver Disease

Fatty liver disease is a common but reversible condition linked to obesity, alcoholism, and type 2 diabetes. In this condition, fat builds up in your liver, making it harder for your liver to complete its normal functions of [9]:

  • Removing toxins from your blood
  • Digesting food
  • Storing energy

Notably, participants in the Phase 2 Clinical Trials of retatrutide also reported healthy changes in their hemoglobin A1c (a measure of diabetes control), blood pressure, and LDL (unhealthy) cholesterol as they lost weight.[7]

What Are Retatrutide's Side Effects or Risks?

Gastrointestinal (GI) side effects were the most commonly reported side effects in the retatrutide clinical trials [Jaberoff]. Other GLP-1 agonists are known to cause the following GI symptoms:

  • Nausea
  • Bloating
  • Gas (belching and farting)
  • Vomiting
  • Heartburn

As more people take GLP-1 agonists for more extended periods of time, some researchers report seeing an increase in more serious medical complications from these newer drugs, such as obstructions of the GI tract (bowel obstruction, gastroparesis), pancreatitis, and biliary disease.[10]

It is not yet known whether retatrutide will cause the same GI side effects or more severe health complications. Only time will tell as we wait for retatrutide to progress through further clinical safety trials.

Everlywell – Support For Your Weight Loss Journey

Everyone’s reasons for wanting to lose weight are as unique as they are. That is why Everlywell offers you a range of options for achieving a healthy weight. From convenient at-home testing for weight-related health conditions such as diabetes to online weight loss prescriptions, Everlywell is here for you.

The development of robust, experimental medications like retatrutide may make your weight loss journey more successful but also more confusing as you try to choose what is right for you. You know your body, your budget, and your lifestyle best. Everlywell knows you are the expert, so we put you first, directing your weight loss journey.

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References

  1. Glucagon-like peptide agonist (GLP-1) agonists market size & share analysis - growth trends & forecasts (2023 - 2028). Mordor Intelligence. https://www.mordorintelligence.com/industry-reports/glucagon-like-peptide-1-agonists-market. Published 2023. Accessed October 22, 2023.
  2. Stewart, J. Retatrutide: FDA Approval Status. Drugs.com. https://www.drugs.com/history/retatrutide.html. Published July 5, 2023. Accessed October 22, 2023.
  3. News release: Lilly to present new research in the treatment of diabetes and obesity at the American Diabetes Association's® 83rd Scientific Sessions. Eli Lilly. https://investor.lilly.com/news-releases/news-release-details/lilly-present-new-research-treatment-diabetes-and-obesity. Published June 20, 2023. Accessed October 22, 2023.
  4. Jastreboff A, Kaplan L, Frías J, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023; 389:514-526. DOI: 10.1056/NEJMoa2301972
  5. Doggrell SA. Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity? Expert Opin Investig Drugs. 2023;32(5):355-359. doi:10.1080/13543784.2023.2206560
  6. Abdi Beshir S, Ahmed Elnour A, Soorya A, et al. A narrative review of approved and emerging anti-obesity medications. Saudi Pharm J. 2023;31(10):101757. doi:10.1016/j.jsps.2023.101757
  7. Miller, K. Experimental new weight loss drug retatrutide may rival ozempic. Prevention. https://www.prevention.com/weight-loss/a44359639/retatrutide-eli-lilly-weight-loss-drug/. Published June 27, 2023. Accessed October 22, 2023.
  8. Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care. 2011;34(7):1481-1486. doi:10.2337/dc10-2415
  9. Fatty liver disease. MedlinePlus. https://medlineplus.gov/fattyliverdisease.html. Published April 26, 2017. Accessed October 22, 2023.
  10. Weiss T, Carr RD, Pal S, et al. Real-World Adherence and Discontinuation of Glucagon-Like Peptide-1 Receptor Agonists Therapy in Type 2 Diabetes Mellitus Patients in the United States. Patient Prefer Adherence. 2020;14:2337-2345. Published 2020 Nov 27. doi:10.2147/PPA.S277676
  11. Sodhi M, Rezaeianzadeh R, Kezouh A, Etminan M. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. Published online October 05, 2023. doi:10.1001/jama.2023.19574
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