What is Retatrutide? The Next-Gen GLP-1 Drug

Discover retatrutide, a powerful triple-agonist drug in development. Could it eventually outperform semaglutide and tirzepatide?

What is Retatrutide? The Next-Gen GLP-1 Drug featured image

If there’s one drug class that has outpaced competitors in the type 2 diabetes and obesity treatment landscape, it’s GLP-1 RAs. GLP-1 RAs or receptor agonists like semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro) have become household names for their efficacy. But there’s a new contender that promises similar benefits and more—retatrutide.

In fact, scientists refer to it as a “triple-threat drug” due to its remarkable weight loss effects. Let’s learn more about this next-gen medication.

What is Retatrutide?

Retatrutide is an investigational drug under the development of Eli Lilly. To clarify, it’s not your typical GLP-1 as it goes further.

Specifically, it targets three key metabolic receptors:

  • GLP-1 (Glucagon-Like Peptide-1)
  • GIP (Glucose-Dependent Insulinotropic Polypeptide)
  • Glucagon Receptors

This is why it’s known as a triple agonist. Each of these receptors plays a unique role in regulating appetite, glucose, and energy use.

Retatrutide is currently in Phase 3 clinical trials. If the FDA approves it, it could become the most effective medication for weight loss and metabolic control to date.

Retatrutide: The Power of Three

Let’s break down what makes this drug unique.

GLP-1 boosts insulin, reduces appetite, and slows stomach emptying. Hence, you feel full, eat less, and your blood sugar stays steady.

Meanwhile, GIP enhances insulin secretion and may reduce side effects from GLP-1 activation. Thereby, it supports glucose control without adding much risk.

Glucagon receptors, surprisingly, help boost energy expenditure. They increase calorie burn, potentially speeding up weight loss.

Notably, the triple-agonist approach mimics the complex hormonal environment your body experiences during bariatric surgery — but without the scalpel.

According to a 2023 study in the New England Journal of Medicine, retatrutide helped participants lose up to 24.2% of their body weight over 48 weeks. That’s the highest weight reduction ever recorded in a drug trial.

Retatrutide Vs. Competition

The competition is fierce, so how does Retatrutide stack up?

With approval for type 2 diabetes and obesity, semaglutide has demonstrated an average weight loss of 15% in over 68 weeks. In particular, this for trials such as STEP-1, when combined with diet and lifestyle changes. It is currently in the post-marketing phase (Phase 4), having already received FDA approval for weight management.

Meanwhile, tirzepatide is a dual agonist of both GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptors. This dual action provides a more robust metabolic response. For instance, in the SURMOUNT-1 trial, tirzepatide led to an average weight loss of up to 22.5%, significantly outperforming semaglutide. Moreover, tirzepatide has received FDA approval for obesity as of late 2023 and is also in the post-approval phase.

Retatrutide is the most recent of the three and remains in Phase 3 clinical trials. Early trial results have shown particularly promising outcomes, with participants losing up to 24.2% of their body weight over 48 weeks — the most substantial reduction seen to date among obesity medications. However, as retatrutide is still under investigation, more data from larger Phase 3 trials are needed before any regulatory approval.

Although semaglutide changed the game, tirzepatide raised the bar. But retatrutide is aiming to go even further.

“We believe this potential new medicine can deliver even more weight loss than tirzepatide and it could potentially provide additional health benefits,” noted Eli Lilly’s chief scientific and medical officer, Daniel Skovronsky.

Still, there’s a catch — retatrutide does not have approval yet. Until full Phase 3 results come in, semaglutide and tirzepatide remain the top-tier market options.

Beyond Weight Loss

Weight loss isn’t the whole story. Retatrutide may also improve:

  • Blood sugar control
  • Liver fat reduction
  • Insulin sensitivity
  • Inflammation markers

In early trials, retatrutide helped patients with type 2 diabetes lower their A1C levels significantly — sometimes better than GLP-1 drugs alone. A1C levels, which you may also call HbA1c shows a person’s average blood sugar levels over the last 2-3 months.

There’s also growing excitement about Retatrutide’s potential in treating non-alcoholic fatty liver disease (NAFLD) and cardiometabolic syndrome.

Overall, triple-agonist drugs could be the key to tackling multiple conditions with one therapy.

Retatrutide Side Effects

Yes, and they’re worth noting.

Like other GLP-1 drugs, Retatrutide can cause:

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation

Generally, these effects are dose-dependent and usually occur during early treatment.

Higher doses of Retatrutide, while more effective, also had more side effects in trials. That’s why researchers are exploring gradual dose escalation.

No serious safety issues have emerged, but longer studies are necessary to confirm cardiovascular and long-term safety.

What’s Next for Retatrutide?

Eli Lilly is running multiple Phase 3 trials for Retatrutide, with results expected by February 2026.

If successful, FDA approval could be in 2026 — and Eli Lilly would likely market it for obesity and type 2 diabetes.

Overall, industry analysts already predict retatrutide could be a multi-billion-dollar blockbuster, outpacing both Wegovy and Mounjaro.

Nevertheless, questions still remain:

  • Will insurance cover it?
  • Will supply meet demand?
  • Can it compete on price?

We don’t know yet — but the interest in the drug is undeniable.

Future of GLP-1s Is Triple-Agonist

Retatrutide is likely to disrupt everything we know about obesity treatment.

It’s not just another GLP-1 drug. Furthermore, it’s a next-generation therapy with the potential to outperform the best in class.

The triple-action approach could be a game-changer — not just for weight loss, but for the entire field of metabolic medicine.

If early results hold true, retatrutide may be the future of obesity and diabetes treatment.

Frequently Asked Questions

How effective is Retatrutide for weight loss?

In a Phase 2 trial, participants lost up to 24.2% of their body weight in 48 weeks — the most ever seen in a drug study.

Is retatrutide a fat burner?

In a way, yes. One of the drug’s key benefits, apart from regulating blood sugar and curbing appetite is liver fat reduction.

How fast does retatrutide work?

According to clinical trials, it can take as little as four weeks for patients to exhibit weight loss results. On higher doses, moreover, people can expect around a 5% loss in total body weight.

How much does retatrutide cost?

At the moment, retatrutide has not yet received FDA approval so it is not yet on the market.

What happens when you stop taking retatrutide?

According to UCLA Health, you shouldn’t experience adverse withdrawal effects if you stop taking retatrutide. But discontinuing the medication will likely increase your appetite again. Correspondingly, you could regain the weight you’ve lost back.

“Everyone responds differently when they stop taking their medication,” notes Dr. Mopelola Adeyemo, UCLA Health clinical nutrition expert.

“Be conscious of your portion sizes and increase your non-starchy vegetables,” he adds. “The fiber in them can make you feel fuller to account for the increase in hunger you may experience.”

“The best thing to do after two weeks is to reach out to your prescribing physician,” Adeyemo emphasizes.

How often should you take retatrutide?

Since the drug is still in its final clinical trial phase, there is no official dosage schedule yet. Furthermore, it has yet to receive FDA approval.

In one study, participants took retatrutide five times daily, in varying doses of 1mg, 2mg, 4mg, 8mg, and 12 mg. Most started on 1mg or 2mg, and built their way up to higher dosage levels. Generally, this is the practice so as to allow the body to get accustomed to the drug and its effects.

What should I eat on retatrutide?

In Phase 2 of its clinical trials, obese women on the medication lost on average about 28.5% of their body weight. This was over a 48-week period. Meanwhile, men lost an average of 21.2% of their body weight over the same period.

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