Retatrutide weight loss: Could this drug rival bariatric surgery?

The new Eli Lilly weight loss drug retatrutide candidate hasn’t even been approved yet, and it’s already generating media buzz. Phase 2 data on retatrutide and weight loss shows exciting potential, according to the June 2023 issue of The New England Journal of Medicine, and the results look even more promising than those of other medications, like Wegovy® and Mounjaro®.

In the double-blind, phase 2 clinical trial, which examined retatrutide as a weight loss drug, 338 adult participants with obesity or excess weight who didn’t have type 2 diabetes paired weekly injections of the drug with lifestyle changes for 48 weeks. Participants received varying dosages of retatrutide for weight loss, which increased over the course of the trial. During the study, those who took 12 mg—the highest dose—lost an average of 22.5% in body weight, or about 52 pounds by the end of the trial. 

And here’s the eyebrow-raising discovery of the study: By the end of the study, the research suggested that participants hadn’t reached their weight plateau yet. That could mean even more weight loss might be possible when using retatrutide over a longer period.

To help make sense of how retatrutide works, the ways it compares to other medicines used for weight loss, and when it might get approval from the U.S. Food and Drug Administration (FDA), let’s take a look at the ins and outs of what we know about retatrutide weight loss so far. 

What is retatrutide? 

Eli Lilly and Company are testing retatrutide to treat type 2 diabetes and obesity. It works by mimicking three hormones in the gut and, in turn, controls glucose levels, decreases appetite, and increases feelings of fullness. Retatrutide is a weekly injection, combined with lifestyle changes including exercise and healthy eating habits. 

Retatrutide’s clinical trials showed remarkable results in treating excess weight and obesity. Studies of GLP-1 meds used for weight loss, including Wegovy and Mounjaro, found that most, but not all, study participants lost body weight with each drug. However, in the retatrutide weight loss study, all participants taking higher doses of the drug lost weight. 

At the end of the 11-week Phase 2 trial, every participant who took 8 mg or 12 mg of retatrutide lost at least 5% of their body weight. And among those taking 12 mg, more than 9 out of 10 lost 10% or more of their baseline weight, nearly two-thirds lost 20%, almost half lost 25% or more, and a quarter lost 30% or more.

In addition to notable weight loss effects, the Phase 2 research showed health improvements in other areas for participants taking retatrutide (as compared to those in the placebo group), including:

• Glucose levels: 72% of participants who had prediabetes at the start of the study experienced a shift to a normal concentration of glucose in the blood by the end of the study.
• Blood pressure: Many participants taking medication to lower blood pressure at the start of the study had stopped taking at least one blood pressure med by the end of the trial, including 41% of the people receiving the 8 mg dose and 30% receiving the 12 mg dose.

• Cardiometabolic measures: At both the mid- and endpoints of the study, participants showed improvements associated with heart health and metabolism, including blood pressure (both systolic and diastolic), as well as improved levels of hemoglobin A1c, fasting glucose, and insulin (all indicators to measure or monitor the risk or presence of prediabetes or diabetes), as well as lipids (fat in the blood).

How effective is retatrutide weight loss?

Based on the findings from Phase 2 trials, participants lost a notably high percentage of body weight using retatrutide—far ahead of the results for similar weight loss medications. On average, participants taking 15 mg of the medication (the highest dose that was tested) lost up to 22.5% of their body weight by the end of the 72-week trial. That weight loss is about 7.5% higher than that seen in studies for other “G” medications. As a comparison, here are the findings from trials of other weight loss drugs:

• Semaglutide: Participants taking weekly 2.4 mg doses of semaglutide (Wegovy’s active ingredient) lost an estimated average of 14.9% of their body weight by the end of a 68-week trial.
• Tirzepatide: Participants taking 5 mg of tirzepatide each week (Zepbound and Mounjaro’s active ingredient) lost an estimated average of 15% of their body weight by the end of a 72-week trial, and patients taking 15 mg of tirzepatide a week in the same study lost 22.5% of their total body weight.

How does retatrutide work compared to weight loss drugs like Wegovy and Mounjaro?

Like Wegovy and Mounjaro, retatrutide is part of a group of medications known informally as the “G” meds, which mimic gut peptides (aka gastrointestinal hormones), including glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Among other things, these hormones—and the medications that mimic them—help regulate appetite and help you feel fuller after eating and, in turn, lose weight. There are three types of “G” meds:

1. Single agonist medications: Glucagon-like peptide-1 RA medication, or GLP-1 receptor agonist (GLP-1 RA), imitates the single hormone GLP-1 and increases insulin secretion, which slows digestion, reduces the release of glucagon (the hormone that regulates blood glucose), and heightens satiety. Semaglutide medications like Ozempic® or Wegovy, both from Novo Nordisk, are examples of this type of medication.
2. Dual agonist medications: GLP-1/GIP dual agonists can bind to two receptors. Therefore, this medication is thought to be more effective at lowering blood sugar and weight loss than GLP-1 RAs alone. An example of this type of drug is Mounjaro, a brand-name medication for tirzepatide, which the FDA approved as a type 2 diabetes treatment; health care providers can prescribe it off-label for weight management. (In November 2023, the FDA approved tirzepatide—brand name Zepbound™—for chronic weight management in adults with obesity.)
3. Triple agonist medications: This is where retatrutide comes in. This “triple-G” weight loss drug (currently in trials) binds to GIP, GLP-1, and glucagon receptors. This triagonist may also boost metabolism. While research hasn’t yet established precisely why this triple-G weight loss drug has shown such a large percentage of body weight loss compared to the other two types of “G” meds, it’s believed that combining these three receptor agonists may enhance the medication’s effect.

Retatrutide isn’t available yet for public use since trials are ongoing. Ozempic, Wegovy, and Mounjaro are FDA-approved, and all three are part of the toolkit of medications prescribed by Found-affiliated health care providers. 

How is retatrutide administered?

In addition to taking a weekly retatrutide injection in tandem with lifestyle updates, like changes in exercise and eating habits, retatrutide study participants had regular counseling sessions with a health care professional, such as a dietitian. 

What weight loss drugs are available now?  

Taking weight loss drugs, combined with healthy lifestyle guidance, dedicated coaching, and medical monitoring, can make a big difference in successfully reaching your health goals. 

It’s important to work with a health care provider who is trained in obesity medicine. Weight is complex, and each person’s unique biology affects how they lose weight. For personalized support, Found offers a proprietary MetabolicPrintTM assessment to identify the root cause of each person’s weight gain. Found-affiliated clinicians will prescribe weight loss medications to work with your biology. Found also provides health coaching and a lifestyle change program to support successful, sustained weight loss. 

What are the potential side effects? 

The retatrutide side effects are similar to the side effects of GLP-1 and dual agonists. These include nausea, vomiting, diarrhea, and acid reflux. More serious but less common side effects include pancreatitis, gallbladder disease, and worsening of diabetic eye disease. Those with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasias type 2 should not use these drugs. 

The most common side effects participants experienced in the Phase 2 trial for retatrutide were gastrointestinal issues—including mild-to-moderate nausea, vomiting, constipation, and diarrhea. Participants also reported heart rate increases, cardiac arrhythmias, and heightened skin sensitivity.

Find detailed information on specific drug side effects and risks on our dedicated medications page.

Retatrutide availability: Can I get retatrutide now?

In short, no. 

In addition to upbeat press coverage, there’s also troubling news surrounding the drug: Counterfeit versions of retatrutide are popping up on gray-market websites. Beware: These are not the real deal. Retatrutide is still in clinical trials and hasn’t been approved by the FDA. Taking any counterfeit drug is risky. 

To stay safe, don’t take this drug (or any) unless it’s received FDA approval. Always go through a licensed medical provider, like the clinicians at Found, to obtain a prescription.

When will retatrutide be available?

Clinical trials for FDA approval take time, so retatrutide doesn’t have a specific approval date. In the summer of 2023, researchers started Phase 3 clinical trials to assess how effective, safe, and tolerable retatrutide is for chronic weight management in people with obesity and cardiovascular disease. 

If, after moving through the drug approval process, retatrutide is found to be safe and effective, then the FDA could approve it for sale. But, even after FDA approval, it may take time before the drug is on the market. 

If all goes well, retatrutide may be FDA-approved and available to consumers in a few years, possibly by 2026. 

What other options are there for weight loss drugs? 

If you are interested in medical weight loss, other drugs are available on the market. An obesity medicine specialist can personalize a prescription for you to target your biology. The clinicians at Found are trained in obesity medicine. They use your MetabolicPrint profile and your medical and weight history to tailor a treatment plan. They also monitor you throughout your journey and help you reach your weight loss goals. 

About Found

To discover your MetabolicPrint and start your journey with Found, take our quiz. Found is among the largest medically supported weight care clinics in the country, having served more than 200,000 members to date.

GLP-1*

GLP-1 prescriptions, filled through your local pharmacy, are now available as part of Found's weight-loss toolkit. While GLP-1s can be effective for weight loss, they are not clinically appropriate for everyone. Eligibility for a GLP-1 is based on a thorough evaluation of your medical history and lab work. If a GLP-1 is not appropriate for you, our providers will work with you to determine an effective medication for your health profile.