Survodutide, retatrutide, orforglipron: molecules that could surpass Mounjaro are already in advanced clinical trials.
While tirzepatide (Mounjaro/Zepbound) has revolutionized obesity treatment with its dual GIP/GLP-1 action, pharmaceutical research does not stop. Several new-generation molecules are under development, promising even more impressive results. An overview of treatments that could redefine obesity management in the years to come.
Survodutide (Boehringer Ingelheim): the triple agonist glucagon/GIP/GLP-1
Survodutide represents the logical evolution of tirzepatide by adding a third mechanism: the activation of glucagon receptors. Where tirzepatide targets two hormones (GIP and GLP-1), survodutide targets three. The addition of glucagon stimulates lipolysis and thermogenesis, accelerating the burning of stored fat.
The results of the phase 2 study, published in the New England Journal of Medicine in 2024, are remarkable: an average weight loss of 18.7% in 46 weeks at the 4.8 mg dose. The molecule also shows significant benefits on hepatic steatosis (NASH), with a reduction in liver fat content of over 80% in some patients.
Phase 3 trials (SYNCHRONIZE program) are underway and could lead to market authorization as early as 2027. Survodutide could become the reference treatment for patients presenting with both obesity and severe hepatic steatosis.
Retatrutide (Eli Lilly): the triple agonist from the same manufacturer as Mounjaro
Eli Lilly, manufacturer of tirzepatide, is also developing retatrutide, another triple GIP/GLP-1/glucagon agonist. Phase 2 results published in the New England Journal of Medicine (2023) caused a sensation: an average weight loss of 24.2% in 48 weeks at the highest dose (12 mg). This is an absolute record for an anti-obesity drug treatment.
To put these figures into perspective, tirzepatide achieves approximately 20-22% weight loss within the same timeframe. Retatrutide therefore offers an additional gain of 2 to 4 percentage points, which can represent several additional kilograms for patients.
The phase 3 program (TRIUMPH) began in 2024 with trials involving over 40,000 participants. If the results confirm phase 2, retatrutide could obtain its authorization in 2028-2029. Eli Lilly would thus position itself with two complementary molecules: tirzepatide for broad use and retatrutide for the most severe cases.
Orforglipron (Eli Lilly): the revolution of the weight loss pill
All current GLP-1 treatments are injections. Orforglipron could change the game by offering a GLP-1 agonist in daily oral tablet form. This innovation addresses one of the main barriers to the adoption of anti-obesity treatments: the fear of injections.
Phase 2 results, published in the New England Journal of Medicine (2023), show a weight loss of 14.7% in 36 weeks at the 45 mg dose. Although slightly lower than injectables, this result is considerable for an oral treatment. The tolerability profile is comparable to injectable GLP-1 agonists, with transient nausea as the main side effect.
The phase 3 study (ATTAIN) is underway with over 10,000 patients. Orforglipron could be approved as early as 2026-2027. Its arrival on the market would democratize access to GLP-1 treatments by removing the psychological and logistical barrier of injection.
Amycretin (Novo Nordisk): the competitor’s response
Novo Nordisk, manufacturer of Ozempic and Wegovy, is not inactive. Amycretin combines GLP-1 with amylin, a pancreatic hormone that enhances satiety. Early phase 1 results showed a weight loss of 13.1% in just 12 weeks, projecting a potential of 25% or more over one year.
CagriSema, another Novo Nordisk molecule combining semaglutide with cagrilintide (an amylin analogue), demonstrated in phase 3 a weight loss of 22.7% in 68 weeks, surpassing semaglutide alone. This combination strategy illustrates the trend towards increasingly effective multi-target therapies.
Pemvidutide, bimagrumab, and other innovative approaches
Other molecules explore different pathways. Pemvidutide (Altimmune) is a dual GLP-1/glucagon agonist that specifically targets hepatic steatosis. Bimagrumab is a monoclonal antibody that blocks activin receptors, promoting muscle mass gain and fat loss simultaneously — a Holy Grail in obesity treatment.
Research also explores non-hormonal approaches, such as intestinal microbiome modulators, gene therapies targeting weight regulation pathways, and targeted delivery nanoparticles. These avenues, still in the preclinical stage, could transform obesity management in the next decade.
Comparative table of molecules in development
Here is a comparison of the main molecules in the pipeline, based on available clinical data:
| Molecule | Mechanism | Route | Weight loss | Phase | Estimated launch |
|---|---|---|---|---|---|
| Tirzepatide (ref.) | GIP/GLP-1 | Weekly injection | 20-22% | Commercialized | Available |
| Retatrutide | GIP/GLP-1/Glucagon | Weekly injection | 24.2% | Phase 3 | 2028-2029 |
| Survodutide | GLP-1/Glucagon | Weekly injection | 18.7% | Phase 3 | 2027 |
| Orforglipron | GLP-1 | Oral tablet | 14.7% | Phase 3 | 2026-2027 |
| CagriSema | GLP-1/Amylin | Weekly injection | 22.7% | Phase 3 | 2026 |
| Amycretin | GLP-1/Amylin | Oral tablet | ~25% (proj.) | Phase 2 | 2028+ |
What this means for current Mounjaro patients
If you are currently on tirzepatide, these advances are excellent news. Tirzepatide remains the reference treatment in 2026, with the best benefit/risk ratio among available options. The molecules under development will eventually offer more choices and potentially even more effective options.
In the meantime, it is important to maximize the benefits of your current treatment by combining tirzepatide with a balanced diet, regular physical activity, and rigorous medical follow-up. The MounjaGO application helps you track your progress and prepare for your medical consultations with precise data.
FAQ: Next generation after Mounjaro
Will retatrutide be available in France?
Phase 3 trials include European centers. If the results are positive, a European MAA (Marketing Authorization Application) is planned around 2028. Availability in France would then depend on evaluation by the HAS (Haute Autorité de Santé) and price negotiations.
Can one switch from Mounjaro to a new-generation treatment?
Yes, transitions between GLP-1 treatments are possible under medical supervision. Your doctor will assess whether a new treatment offers a better benefit/risk ratio in your specific situation.
Will oral orforglipron be as effective as injections?
Phase 2 data show slightly lower efficacy (14.7% vs 20-22% for injectables). However, for patients who do not tolerate injections, it is a promising alternative with significantly superior results compared to existing oral treatments.