Novo Nordisk A/S (CPH: NOVO-B) has announced that it is advancing its investigational therapy amycretin into phase 3 development after phase 1 and phase 1b/2a trials demonstrated significant weight loss and favorable safety outcomes in people with overweight or obesity. The Danish pharmaceutical company presented results for both subcutaneous and oral formulations at the American Diabetes Association’s (ADA) 85th Scientific Sessions in Chicago and published the full trial data in The Lancet on June 20, 2025. Amycretin is the first drug candidate to combine glucagon-like peptide-1 (GLP-1) and amylin receptor agonism into a single molecule, offering a differentiated mechanism in the competitive obesity therapeutics space.
The clinical data showed that amycretin delivered weight loss outcomes of up to 24.3% in subcutaneous format and up to 13.1% in oral format over treatment durations ranging from 12 to 36 weeks. These results, coupled with a safety profile consistent with existing GLP-1 and amylin receptor drugs, support Novo Nordisk’s plans to initiate large-scale phase 3 trials in the near term.
What were the key findings from Novo Nordisk’s subcutaneous amycretin phase 1b/2a clinical trial data?
The once-weekly subcutaneous amycretin formulation demonstrated clear dose-dependent weight loss effects in the 125-person trial, which included both dose-escalation and maintenance phases across 1.25 mg, 5 mg, 20 mg, and 60 mg cohorts. Patients receiving the 60 mg dose over 36 weeks experienced a mean body weight reduction of 24.3%, compared to just 1.1% in the placebo arm. The 20 mg and 5 mg doses led to mean reductions of 22.0% and 16.2%, respectively, while the lowest dose still achieved a 9.7% reduction.
No weight plateau was observed at any dose level, suggesting longer treatment durations may yield further weight loss. The treatment-emergent adverse events (TEAEs) reported in this study were primarily gastrointestinal in nature—such as nausea and diarrhea—and increased with dose, but were mostly mild to moderate and resolved by the study’s end. Only a small number of participants discontinued due to tolerability, with most dropouts linked to unrelated factors.
How did oral amycretin perform in its phase 1 trial in terms of weight reduction and tolerability?
The once-daily oral amycretin trial enrolled 144 participants with overweight or obesity and evaluated both single and multiple ascending doses over 12 weeks. At the highest dose tier—administered as 2 x 50 mg—participants experienced a mean weight loss of 13.1%. The 50 mg once-daily group reported a 10.4% average weight reduction, both significantly higher than the 1.2% reduction observed in the placebo arm.
No weight loss plateau was observed within the 12-week timeframe. Like its injectable counterpart, oral amycretin was well tolerated with a dose-proportional increase in gastrointestinal side effects that were consistent with GLP-1 and amylin receptor activation. There were no serious adverse events or unexpected safety signals, strengthening its profile as a candidate for further development in the oral anti-obesity segment.
What differentiates amycretin from existing GLP-1-based obesity therapies such as semaglutide and tirzepatide?
Amycretin is designed as a unimolecular agonist targeting both the GLP-1 and amylin receptors, in contrast to semaglutide, which targets GLP-1 alone, and tirzepatide, which activates both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. Amylin, a hormone co-secreted with insulin, plays a key role in satiety and slows gastric emptying. By stimulating both GLP-1 and amylin receptors, amycretin is expected to exert a stronger and more sustained effect on appetite suppression and metabolic regulation.
This differentiated mechanism could allow Novo Nordisk to position amycretin as a next-generation therapy, particularly in patients who exhibit suboptimal responses or tolerability to current GLP-1-only agents. Executive vice president of development Martin Holst Lange stated that the dual-agonism approach offers complementary pathways in appetite control and represents a potential step-change in therapeutic innovation for obesity management.
How do institutional investors and analysts perceive the amycretin development as part of Novo Nordisk’s long-term obesity strategy?
Analysts view the early amycretin data as a major strategic inflection point for Novo Nordisk’s obesity franchise. With semaglutide already a global blockbuster under the Wegovy and Ozempic brands, and increased pressure from Eli Lilly’s dual-agonist tirzepatide, amycretin’s progress offers Novo Nordisk a clear opportunity to expand its dominance. Institutional investors have responded positively to the dual-format approach—injectable and oral—seeing it as a way to broaden market reach and accommodate diverse patient preferences.
The ability to offer an oral option could be especially impactful in geographies where injections are less culturally accepted or logistically feasible. If phase 3 results replicate the magnitude of weight loss and safety seen in the current data, some investors believe amycretin could command a substantial share of the global obesity treatment market and even extend Novo Nordisk’s lead in the metabolic disease segment well into the 2030s.
What are the next steps in Novo Nordisk’s clinical and regulatory roadmap for amycretin?
Novo Nordisk has confirmed its intent to proceed with phase 3 trials for both subcutaneous and oral formulations of amycretin. These studies will likely include thousands of participants and run over longer durations—potentially 52 weeks or more—to fully evaluate sustained weight loss, cardiovascular risk markers, glycemic control, and other metabolic endpoints.
The company has not disclosed exact trial start dates or endpoints but is expected to begin enrolling patients before the end of 2025. Regulatory submissions in major markets including the United States, European Union, and Asia-Pacific regions could follow within the 2026–2028 timeframe if outcomes remain positive. Analysts also expect companion cardiovascular outcome trials (CVOTs) to be initiated in parallel, given the growing focus on holistic obesity treatment benefits beyond weight reduction alone.
How does amycretin fit within the broader evolution of obesity pharmacotherapy and metabolic disease innovation?
Amycretin’s entry into late-stage development represents a broader shift toward multi-pathway hormonal therapies in metabolic medicine. First-generation GLP-1 drugs were largely focused on glycemic control for type 2 diabetes, but the success of high-dose GLP-1 formulations in obesity has unlocked new commercial and clinical potential. The next wave of drug development now appears centered on combining receptor targets—GLP-1, GIP, amylin, and others—into more comprehensive solutions for obesity, diabetes, and related cardiometabolic conditions.
Novo Nordisk’s amycretin marks the first such effort to combine GLP-1 and amylin receptor agonism in a single molecule, rather than co-formulating separate biologics. This design could streamline production, dosing, and regulatory approval processes, offering practical advantages in addition to therapeutic efficacy. If successful, amycretin could set a new benchmark for combination therapies in the category and raise expectations for how future anti-obesity drugs are formulated and delivered.
What does the emergence of amycretin signal for competitive dynamics in the obesity drug market?
Amycretin’s advancement to phase 3 comes at a time of heightened competition in the global obesity market, with Eli Lilly’s tirzepatide already generating strong momentum and Pfizer, Amgen, and smaller biotechs exploring next-generation GLP-1 alternatives. However, Novo Nordisk’s extensive experience in obesity drug manufacturing, physician education, and global regulatory engagement gives it a structural edge.
Experts believe that amycretin, particularly in its oral format, could defend Novo Nordisk’s position against rivals entering the space with less mature pipelines. As pricing pressure, manufacturing capacity, and patient adherence continue to dominate payer discussions, the ability to deliver efficacy with tolerability—and in multiple delivery formats—may prove critical.
If approved, amycretin could redefine combination receptor agonism in obesity management and extend Novo Nordisk’s leadership even further beyond semaglutide-era benchmarks.
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