The GLP-1 Pipeline: Retatrutide, CagriSema, Amycretin and What Comes Next

New weight loss drugs in development aim to go further than today's GLP-1 medicines, by acting on more hormone pathways, lasting longer between doses, or coming as tablets. The most advanced include retatrutide (a "triple agonist"), CagriSema (semaglutide combined with an amylin analogue) and amycretin (a single molecule acting on GLP-1 and amylin receptors). Some have produced striking trial results, but at the time of writing none of these three is licensed in the UK, and they are available only within clinical trials. This guide explains how they work, what the evidence shows and what to be wary of.

Where things stand today

To understand the pipeline, it helps to know what is already licensed. At the time of writing, the UK has:

• Mounjaro (tirzepatide): a weekly injection acting on GIP and GLP-1 receptors, recommended by NICE (TA1026).
• Wegovy (semaglutide): a weekly injection, recommended by NICE (TA875). In January 2026 the MHRA authorised a higher maximum dose of up to 7.2mg weekly for adults with obesity (BMI of 30 or more).
• Liraglutide (Saxenda and generics): an older daily injection.
• Wegovy tablets (oral semaglutide): a daily tablet authorised by the MHRA in June 2026.
• Foundayo (orforglipron): a daily small-molecule tablet authorised by the MHRA in August 2026.

Neither of the tablets had been recommended by NICE for NHS use at the time of writing. For an overview of the current options, see every UK weight loss injection compared and our hubs for weight loss injections and oral GLP-1s.

Many pipeline medicines are being measured against tirzepatide, which produced average weight loss of about 21% at the highest dose in SURMOUNT-1 (NEJM, 2022), and against semaglutide, which in SURMOUNT-5 produced less weight loss than tirzepatide. See our analysis of SURMOUNT-5.

How new medicines reach patients

New medicines pass through several stages before they are routinely available.

Results announced in a company press release ("topline results") are an early summary. Full peer-reviewed publication usually follows months later and provides much more detail on side effects, who was studied and how results were analysed. We point out where results were topline only.

Retatrutide: the "triple agonist"

How it works

Retatrutide, developed by Eli Lilly, is a once-weekly injection that acts on three hormone receptors:

• GLP-1, which reduces appetite and slows stomach emptying
• GIP, the second target of tirzepatide, which appears to enhance the effects of GLP-1 and may improve tolerability
• Glucagon, which may increase energy expenditure and fat breakdown, particularly in the liver

Adding glucagon activity is the main innovation. The idea is that a medicine which reduces intake and also increases energy use could produce larger weight loss.

What the trials show

The phase 2 trial (New England Journal of Medicine, 2023) included adults with obesity, or overweight with a weight-related condition, without diabetes. At 48 weeks, people on the highest dose (12mg) had lost about 24% of their body weight on average, compared with about 2% on placebo. Weight was still falling at the end of the trial in the higher-dose groups.

The phase 3 TRIUMPH programme reported topline results in 2026. According to Eli Lilly's announcement in May 2026, TRIUMPH-1, in over 2,300 adults with obesity, found average weight loss at 80 weeks of about 18% on 4mg, 24% on 9mg and 25% on 12mg, compared with about 4% on placebo, with higher figures reported in some analyses. TRIUMPH-2 and TRIUMPH-3, in people with obesity and major weight-related conditions, also met their main weight-loss goals according to topline results announced in July 2026. Full peer-reviewed publications were awaited at the time of writing.

Side effects and open questions

As with other incretin medicines, gastrointestinal side effects were the most common in trials. The phase 2 trial also noted dose-related increases in heart rate, which peaked and then declined, and unusual skin sensations (dysaesthesia) have been reported in some later retatrutide trials. Questions remain about:

• How much muscle is lost alongside fat at very high levels of weight loss
• Whether weight loss can be "too much" for some people, and how doses should be tailored
• The long-term effects of glucagon receptor activation
• Cardiovascular outcomes, which are being studied in separate trials

UK status

Retatrutide is not authorised in the UK or elsewhere at the time of writing. Regulatory submissions had not been completed, and approval is not expected before 2027 at the earliest according to public reporting. It is not available outside clinical trials.

CagriSema: semaglutide plus amylin

How it works

CagriSema, developed by Novo Nordisk, is a once-weekly injection combining two medicines in one pen:

• Semaglutide 2.4mg, the active ingredient in Wegovy
• Cagrilintide 2.4mg, a long-acting analogue of amylin

Amylin is a hormone released by the pancreas alongside insulin. It signals fullness to the brain and slows stomach emptying through pathways that partly differ from GLP-1. Combining the two aims to boost weight loss beyond semaglutide alone.

What the trials show

REDEFINE 1 (New England Journal of Medicine, 2025) included over 3,400 adults with obesity, or overweight with a weight-related condition, without diabetes. At 68 weeks, average weight loss was about 20% with CagriSema compared with about 3% on placebo. The trial also included groups taking each component alone, and the combination produced more weight loss than either. The trial allowed flexible dosing, and many participants stayed on lower doses, which complicates interpretation.

REDEFINE 2, in adults with type 2 diabetes, also showed greater weight loss than placebo, though, as with other medicines, the average loss in people with diabetes was smaller.

The REDEFINE 1 result was below some expectations set before the trial and broadly similar to tirzepatide's results in SURMOUNT-1, although these were separate trials. Further phase 3 trials, including a head-to-head comparison with tirzepatide, were under way at the time of writing.

UK status

Novo Nordisk submitted CagriSema to the US Food and Drug Administration, with a decision expected in 2026. At the time of writing, it was not authorised in the UK. Check the MHRA for any update.

Amycretin: one molecule, two targets

How it works

Amycretin, also from Novo Nordisk, is a single molecule designed to activate both GLP-1 and amylin receptors. Unlike CagriSema, which combines two separate medicines, amycretin achieves both actions in one compound. It is being developed in two forms:

• A once-weekly injection
• A once-daily tablet

What the trials show

Amycretin has been studied in early-phase trials. A phase 1b/2a trial of the weekly injection, published in The Lancet in 2025, reported average weight loss of around 22% at 36 weeks at the highest dose tested, in a small number of participants. A separate early trial of the tablet also reported meaningful weight loss over a short period. These were small, short trials designed mainly to assess safety and dosing, so the results are promising but preliminary.

Novo Nordisk began a phase 3 programme, called AMAZE, for both forms in 2026. Results are not expected for some time.

UK status

Amycretin is investigational and not licensed anywhere. It is available only within clinical trials.

Other medicines in development

Several other approaches are in clinical trials. This is not a complete list, and details change frequently.

Themes in the pipeline

Looking across these medicines, several trends stand out:

• More targets. Adding glucagon or amylin activity to GLP-1 to increase weight loss or improve tolerability.
• Less frequent dosing. Monthly injections could make long-term treatment easier.
• Tablets. Following oral semaglutide and orforglipron, more oral options are being developed, partly because tablets may be easier to manufacture at scale.
• Quality of weight loss. Increasing attention on preserving muscle and bone, not just reducing weight. See preserving muscle on GLP-1 treatment.
• Maintenance. Trials designed specifically to study keeping weight off after initial loss, including with lower doses or different medicines.
• Outcomes beyond weight. Trials looking at heart disease, kidney disease, fatty liver disease, sleep apnoea and osteoarthritis, following the SELECT trial of semaglutide.

Recently licensed: what changed in 2026

Several developments that were "pipeline" until recently are now authorised in the UK. They show how quickly the field is moving.

Higher-dose Wegovy

In January 2026, the MHRA authorised a maximum Wegovy dose of up to 7.2mg weekly for adults with obesity (BMI of 30 or more), but not for people with a BMI below 30 or for the cardiovascular-risk indication. The STEP UP trial reported average weight loss of nearly 21% at 72 weeks with 7.2mg, compared with about 17.5% with 2.4mg, with a similar overall safety profile. NHS use requires NICE's consideration. See our Wegovy dosing guide.

Wegovy tablets

Oral semaglutide 25mg was authorised in June 2026 for weight management, based mainly on the OASIS 4 trial. See our oral semaglutide guide.

Foundayo (orforglipron)

The MHRA authorised orforglipron in August 2026, making the UK the first country in Europe to do so. It is a small-molecule tablet without food or water restrictions. NICE was assessing it for NHS use at the time of writing. See our Foundayo guide.

How to read headlines about new weight loss drugs

News about obesity medicines moves fast, and headlines often focus on the single largest number from a trial. A few questions can help you judge what a result really means.

Which figure is being quoted?

Many trials report two estimates of weight loss. One counts everyone who started the trial, including those who stopped the medicine early (often called the "treatment policy" or "treatment regimen" estimate). The other estimates what happens if everyone takes the medicine as intended (the "efficacy" estimate). The efficacy figure is always higher, and press releases often lead with it. Neither is wrong, but they answer different questions.

Which dose, and for how long?

Headline figures usually come from the highest dose tested. Lower doses, which some people may stay on because of side effects, typically produce less weight loss. Trial length matters too: a result at 80 weeks is not directly comparable with one at 48 or 68 weeks, especially if weight was still falling when the trial ended.

Who was in the trial?

People with type 2 diabetes generally lose less weight on these medicines than people without diabetes. Trials also differ in average starting weight, age, sex and ethnicity, and in the amount of lifestyle support offered. A result from one population may not translate directly to another.

Was it compared with placebo or with another medicine?

Most trials compare a new medicine with placebo. Placing results from separate placebo-controlled trials side by side is a rough guide only. Head-to-head trials, such as SURMOUNT-5 (tirzepatide versus semaglutide), give much more reliable comparisons, but they are less common.

Is it peer reviewed?

Topline results from a company announcement are an early summary. Peer-reviewed publication, usually in journals such as the New England Journal of Medicine or The Lancet, provides the full methods, side-effect data and analysis. Some important details, such as discontinuation rates or rare side effects, only become clear at that stage.

What about side effects and stopping rates?

A large average weight loss means little if many people cannot tolerate the medicine. Look for the proportion of participants who stopped because of side effects, and how this changed with dose.

A warning about "pipeline" products sold online

Interest in new medicines has led to unlicensed products being sold online, particularly retatrutide, often labelled "for research use only" or "not for human consumption". These products:

• Are not authorised medicines and have not been assessed by the MHRA for quality, safety or effectiveness
• May contain the wrong substance, the wrong amount or harmful contaminants
• Are supplied without a prescriber's assessment or monitoring
• Have no reliable information on dosing, storage or side effects

The MHRA has repeatedly warned the public against obtaining weight-loss medicines from unregulated sources. Supplying prescription-only medicines without a prescription is illegal in the UK. If you are interested in a pipeline medicine, the legitimate route is a registered clinical trial. Our guide to fake and unlicensed weight loss jabs explains how to spot unsafe products, and getting weight loss injections online safely explains how to check a provider is regulated.

Taking part in a clinical trial

Clinical trials are how new medicines are tested, and participants contribute to the evidence that benefits others. If you are interested:

• Speak to your GP or specialist about suitable studies
• Search the NIHR's "Be Part of Research" service or the ISRCTN registry for trials recruiting in the UK
• Ask the research team about the possibility of receiving placebo, the time commitment, and what happens at the end of the trial

Taking part is voluntary, and you can withdraw at any time.

Should you wait for newer medicines?

It is natural to wonder whether to start treatment now or wait for something more powerful. Some points to consider when discussing this with a prescriber:

• Pipeline medicines may not be approved, or may be approved for narrower groups than expected.
• Timelines are long. Even after authorisation, NICE appraisal and NHS rollout can take years. Tirzepatide's phased NHS rollout, which began in June 2025, is expected to take several years to reach all eligible people.
• More weight loss is not always better for every individual. The right amount depends on health goals and the balance of benefits and side effects.
• Current medicines have substantial evidence, including long-term and cardiovascular outcome data for semaglutide.
• Switching is possible later. People on current medicines may be able to move to newer options if they become available and appropriate.

Our guide to long-term GLP-1 use looks at what is known about staying on treatment.

Cost and access in the future

We do not quote prices. In general, new medicines often launch at higher prices, and prices can change as competition increases. The September 2025 rise in Mounjaro's UK list price showed that prices can also move upwards. NHS access will depend on NICE's assessment of cost-effectiveness. For current options and what affects their cost, see our prices page, and to compare regulated services, our provider comparison.

When to speak to a professional

Speak to your GP, pharmacist or prescriber if you are considering weight-management treatment, wondering whether a current or future medicine might suit you, or interested in taking part in a clinical trial. Tell them about any history of pancreatitis, gallbladder disease, thyroid cancer, kidney problems or eating disorders, and if you are pregnant, planning pregnancy or breastfeeding. Never use a weight-loss medicine that has not been prescribed for you.

Seek urgent medical help through NHS 111, or call 999 in an emergency, if you are taking any weight-loss medicine, licensed or not, and experience:

• Severe, persistent abdominal pain, possibly spreading to the back, with or without vomiting
• Repeated vomiting or diarrhoea that stops you keeping fluids down, or signs of dehydration
• A racing or irregular heartbeat, chest pain or fainting
• Yellowing of the skin or eyes
• Signs of a severe allergic reaction, such as swelling of the face or throat or difficulty breathing

For up-to-date information on licensed medicines, check the MHRA and the Summary of Product Characteristics on medicines.org.uk. You can browse all our guides at /guides.