Retatrutide Weight Loss Results: Retatutride vs Tirzepatide vs Semaglutide

As the search for effective weight loss solutions continues, retatrutide, Eli Lilly’s new weight loss medication, has emerged as a potential new superstar. While it is not yet available on the market, ongoing retatrutide clinical trials have shown remarkable results, leaving everyone wondering whether retatrutide can outperform existing treatments like semaglutide and tirzepatide.

How does retatrutide work?

Retatrutide’s mechanism of action is similar to other weight loss and type 2 diabetes medications. What sets retatrutide apart is its unique ability to engage three receptors simultaneously:

GIP (Gastric Inhibitory Polypeptide) receptor
GLP-1 (Glucagon-Like Peptide-1) receptor
GCG (Glucagon) receptor

This puts retatrutide into a new medication class known as triple agonists. By activating these three receptors, retatrutide effectively improves glucose control and supports weight loss by:

Enhancing insulin secretion and sensitivity.
Suppressing glucagon release to prevent excessive glucose production.
Slowing gastric emptying and promoting satiety, which can help reduce caloric intake.

Retatrutide clinical trials and preliminary results

Eli Lilly, the manufacturer of retatrutide, completed their Phase II trials and released results in June 2023. This phase was a 48-week trial focusing on individuals with obesity, or overweight with weight-related conditions—except type 2 diabetes.

The results of the study were evaluated at two key points: halfway through the trial at 24 weeks and again at the conclusion of the trial at 48 weeks. The chart below shows the retatrutide weight loss results based on the dose and duration:

Dosage	24-Week Results	48-Week Results
1 mg	7.2%	8.7%
4 mg	12.9%	16.3%
8 mg	17.3%	23.9%
12 mg	17.5%	24.2%
Placebo	1.6%	2.1%

The retatrutide clinical trials are still underway with a planned Phase IV beyond the current Phase III. If all goes well, FDA-approval and release will likely not happen until 2026 or beyond.

Retatrutide vs Semaglutide

Retatrutide is a triple agonist medication in development that activates three receptors—GIP, GLP-1, and GCG. Semaglutide (Ozempic, Wegovy) is a single agonist, specifically a GLP-1 medication.

Semaglutide has been on the market for some time and has shown clinically significant weight loss results, earning it FDA approval under the brand name Wegovy. Retatrutide is still in development.

While semaglutide effectively aids in weight loss by improving appetite control and glucose regulation, retatrutide’s unique triple-action approach may offer enhanced benefits. With retatrutide clinical trials still ongoing, there’s no way to tell which medication will be the better choice.

Retatrutide vs semaglutide results

Both retatrutide and semaglutide have been shown to result in clinically significant weight loss. In semaglutide’s 68-week trial, half of the participants lost 15% of their body weight, while one-third lost 20%.

With retatrutide, weight loss was achieved in a much shorter time period. Participants on the higher doses of retatrutide lost an average of 17% of their body weight in just 24 weeks, with weight loss continuing to progress to 23-24% by the 48-week mark.

Retatrutide vs tirzepatide

Like retatrutide, tirzepatide (Mounjaro, Zepbound) was a first-of-its-kind treatment that has caught a lot of attention for its results. Another Eli Lilly medication, tirzepatide is a dual-agonist activating both the GLP-1 and GIP receptors. By activating the GLP-1, GIP, and GCG receptors, retatrutide has the potential to offer even more benefits.

Tirzepatide is relatively new to market, only gaining FDA approval for weight loss (under Zepbound) in November 2023. Many insurance companies have yet to add tirzepatide to their formulary, but will likely do so in the next year.

Retatrutide vs tirzepatide results

Retaturitide and tirzepatide both show promising weight loss results in a short period. During the tirzepatide trial, participants experienced an average weight loss of 6.9% after 12 weeks. Retatrutide showed a 7.2% weight loss at the lowest dose over 24 weeks. Remember that a 5% weight loss can show health improvements for those with obesity.

After 84 weeks, tirzepatide participants achieved an impressive mean weight loss of 26.6%. The retatrutide participants lost around 24.2% over 48 weeks at the highest dose.

Retatutride vs Tirzepatide vs Semaglutide: A Comparison

Medication	Weight Loss	Duration	Type of Receptor Agonist	FDA-approval for Weight Loss
Retatrutide	24.2%	48 weeks	Triple	Trials Ongoing
Semaglutide	20%	68 weeks	Single	Yes, under Wegovy
Tirzepatide	26.6%	84 weeks	Dual	Yes, under Zepbound

Is Retatrutide safe and effective for weight loss?

Since clinical trials for retatrutide are still ongoing, it’s too early to provide a definitive answer regarding its overall effectiveness and safety.

In clinical trials, retatrutide has shown promising results for weight loss, but like any medication, it comes with potential side effects and considerations. Phase II trial results did include data on adverse events:

A significant percentage of participants (73% to 94%) reported adverse events while taking retatrutide, particularly in the higher 8-mg and 12-mg groups.
The most commonly experienced side effects were gastrointestinal issues, including nausea, diarrhea, vomiting, and constipation.
Digestive side effects mainly occurred during the dose escalation phase and were mostly mild to moderate in severity—lower starting doses seemed to lessen this severity.
There were slight increases in certain digestive enzyme levels, such as amylase and lipase. But there was only one reported serious case of pancreatitis.
Participants taking higher doses of retatrutide experienced an increase in heart rate during the first 24 weeks, after which it decreased.
No serious cases of low blood sugar or significant complications like thyroid cancer were reported among participants.
Some individuals (7% of those on retatrutide compared to 1% on placebo) experienced skin sensitivity, but these cases were not serious.

Downsides of Rapid Weight Loss

In addition to potential side effects from the medication, it’s important to consider the implications of rapid weight loss. Yes, retatrutide shows clinically significant results in as little as 24 weeks, but losing weight too quickly can lead to other issues.

You’ll need to consider issues like:

Muscle Loss: Rapid weight loss often results in the loss of lean muscle mass along with fat. This can decrease strength and metabolism, making it harder to maintain weight loss. You’ll need to try and prevent muscle loss.
Nutritional Deficiencies: Losing weight too quickly may lead to inadequate nutrient intake, which can result in deficiencies.
“Ozempic Face” or “Ozempic Butt”: These terms refer to changes in facial and body appearance due to significant weight loss, often leading to sagging skin or a deflated look.
Telogen Effluvium (TE): This is a temporary form of hair loss triggered by rapid weight loss or significant trauma. It occurs when hair follicles enter a resting phase and may lead to noticeable thinning of hair.

Ready to lose weight?

Retatrutide is still undergoing clinical trials and probably won’t be available until at least 2026. If you’re ready to kick off your weight loss journey now, don’t worry—there are plenty of effective options out there!

Heally can connect you to a knowledgeable doctor who can help you find the best way forward. You don’t have to navigate this alone; let’s find the right solution together! Register today.