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Dual agonists vs Triple agonists: Which are better?
Medically reviewed by
Alexandra Cristina Cowell, Writer & Clinical Content Reviewer
The conversation is now dominated by two categories of treatment:
- Dual agonists: Medications that target two metabolic hormones at the same time (typically GLP-1 and GIP) to quieten ‘food noise’, slow digestion, and improve how your body processes blood sugar.
- Triple agonists: The next leap forward in metabolic science. These target three hormones at once, adding glucagon to the GLP-1 and GIP foundation to reduce appetite while actively helping your body to burn more calories at rest.
On paper, targeting three hormones sounds like an automatic victory. But in reality, choosing the ‘better’ option is a fine balance between maximum weight loss potency, real-world availability, and what your body can actually tolerate.
To see how this science plays out in practice, let’s compare the UK’s current gold standard, Mounjaro, to one of the most anticipated pipeline drugs, Retatrutide.
Mounjaro vs Retatrutide
Mounjaro (tirzepatide) is fully approved by the MHRA and widely available for both type 2 diabetes and weight loss.
Retatrutide, on the other hand, is Eli Lilly’s next-generation follow-up. While it’s generating massive headlines globally and in the UK scientific community, it’s still an experimental drug and can’t yet be legally prescribed.
The core difference between them comes down to how many metabolic pathways they target: Mounjaro is a dual hormone agonist, while Retatrutide is a triple hormone agonist (often nicknamed the ‘triple G’).
Mounjaro mimics two natural gut hormones: GLP-1 (which slows stomach emptying and signals fullness to your brain) and GIP (which improves how your body responds to sugar and regulates appetite and fat cells).
Retatrutide, on the other hand, targets the same hormones as Mounjaro plus one other: glucagon. Glucagon helps increase your body’s energy expenditure (burning more calories at rest) and specifically targets fat accumulation in the liver.
Studies suggest Retatrutide may be more effective, too. While clinical trials show adults on the highest dose of Mounjaro lose an average of 22.5% of their body weight after 72 weeks (when paired with diet and exercise), recent Phase 3 trial data (from the TRIUMPH-1 study released in May 2026) shows even better results. Participants with severe obesity on the highest doses achieved up to 30% body weight reduction over two years, numbers previously only seen with bariatric surgery.
Do Mounjaro and Retatrutide cause the same side effects?
The short answer is yes and no. Mounjaro and Retatrutide do share the same baseline of gastrointestinal side effects (like nausea and constipation), however, because Retatrutide targets a third hormone (glucagon), it introduces a couple of side effects not seen with Mounjaro, specifically related to heart rate and skin sensitivity.
Which side effects do they share?
Because both medications slow down your digestive system and signal fullness to the brain, they share the standard ‘GLP-1 family’ side effects. These typically peak when you start treatment or you’re stepping up your doses (titration) and improve as your body adjusts:
- Nausea
- Vomiting
- Diarrhoea
- Constipation
- Decreased appetite
- Acid reflux
- Fatigue
- Headaches
Where Retatrutide differs
Because Retatrutide also targets glucagon, this alters how it affects your body, resulting in a couple of side effects not usually seen with Mounjaro:
1. A faster resting heart rate
Glucagon increases your body’s energy expenditure (which means you’ll burn more calories at rest), which naturally impacts your cardiovascular system.
So while Mounjaro typically causes a very mild resting heart rate increase of about 2.1 to 5.4 beats per minute, Retatrutide has shown a more noticeable average increase of 6.7 to 7 beats per minute. Trials also noted a mild increase in transient, non-serious irregular heartbeats or palpitations in 2% to 11% of patients (depending on the dose).
2. Skin sensitivity (dysesthesia)
A unique side effect called dysesthesia has emerged in clinical trials of Retatrutide, affecting around 21% of patients on the highest dose. Patients describe it as an altered sense of touch where their skin feels abnormally sensitive, burning, tingling, or tender against clothing or water.
Is Retatrutide better than Mounjaro?
Whether Retatrutide is ‘better’ than Mounjaro depends entirely on what ‘better’ means to you. If you’re looking strictly at raw weight loss data, Retatrutide may be the winner. But if you’re looking at what’s safe, available, and tolerable to take right now, Mounjaro seems to be the clear winner. However, the best way to see how Mounjaro and Retatrutide stack up would be to compare them directly in a head-to-head trial.
Weight loss results
If we look solely at the clinical data, Retatrutide may outperform Mounjaro.
- Mounjaro’s landmark trials showed an average weight loss of around 22.5% after 72 weeks.
- Phase 3 trial data for Retatrutide showed that adults with severe obesity lost an average of up to 30% of their body weight over two years.
And because Retatrutide targets three metabolic hormones (GLP-1, GIP, and glucagon) instead of Mounjaro’s two, it doesn’t just switch off your appetite; it actively coaxes your body into burning more calories at rest and clears fat out of your liver faster.
As a result, Retatrutide is widely considered the most potent weight loss drug ever made.
Practicality and safety
While Retatrutide wins on paper, Mounjaro wins in the real world for a few key reasons:
- It’s actually available. Mounjaro is fully approved by the MHRA and sits on UK pharmacy shelves today. You can get it privately or via the NHS if you meet the criteria. Retatrutide, on the other hand, is still an investigational drug. It’s not expected to clear regulatory hurdles and launch in the UK until late 2027 or 2028 at the earliest.
- It’s easier to tolerate. In clinical trials, about 11% of people stopped taking Retatrutide due to side effects (mostly severe nausea and vomiting). With Mounjaro, the dropout rate was around half of that.
- It has fewer irregular side effects. Mounjaro’s side effects are almost entirely confined to your stomach. Whereas Retatrutide can introduce unique complications due to its glucagon targeting.
The verdict
| If your priority is… | The winner* | Why? |
|---|---|---|
| Maximum possible Weight loss | Retatrutide | Achieves up to 30% weight loss, approaching bariatric surgery levels. |
| Immediate availability | Mounjaro | Legally prescribable right now, Retatrutide is years away. |
| Fewer side effects and dropouts | Mounjaro | Better tolerated with a much lower rate of discontinuation. |
| Reversing fatty liver disease | Retatrutide | The glucagon component specifically targets and reduces liver fat. |
*The options we’ve highlighted as the ‘winner’ are based on the evidence currently available. However, the best treatment for you will depend on your individual circumstances. That’s why it’s important to discuss your options with your clinician, who can help you choose the treatment that’s most suitable for you.
When can I buy Retaturide?
Because Retatrutide is still in clinical development, it doesn’t have a UK licence yet. The earliest we might see MHRA approval is late 2027, and a subsequent NICE recommendation for NHS funding would likely push its arrival on the NHS back to 2028 or 2029.
And because of the huge online hype, authorities have heavily cracked down on underground vendors. UK police and regulatory officers have recently seized thousands of doses of fake, unregulated ‘research-grade’ Retatrutide from illegal labs across the country. These grey-market products are completely untested for human safety, highly prone to contamination, and illegal to buy or sell for personal use.
So while Retatrutide may represent the future of obesity treatment, it’s important to remember that Mounjaro is the gold standard of the present. If you’re looking to start making positive changes to your health now, waiting years for an unreleased drug is a less preferable option when there’s a highly effective option sitting on the shelf today.
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