Hormonal
NNC9204-1177, a glucagon/GLP-1 receptor co-agonist, produces dose-dependent, clinically relevant weight loss (up to 12.6%) in adults with overweight or obesity, but its clinical development was halted due to unexpected safety signals including increased heart rate, impaired glucose tolerance, and elevated inflammatory markers.
NNC9204-1177 is not available for clinical use because it caused unacceptable side effects like rapid heart rate and inflammation, despite causing significant weight loss. Do not seek this specific compound. However, the mechanism (glucagon/GLP-1 co-agonism) suggests that combining these pathways can be more effective for weight loss than GLP-1 alone, provided safety is managed. Current approved GLP-1 agonists (like semaglutide) do not have this glucagon component and thus avoid this specific safety profile.
Although treatment with NN1177 was associated with dose-dependent and clinically relevant weight loss, the observed safety signals precluded further clinical development.
Why this rating
Phase 1 randomized, placebo-controlled trials with robust safety monitoring, though limited by early termination and lack of long-term data.
Source
Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity
Martin Friedrichsen et al. · Molecular Metabolism · 2023
DOI 10.1016/j.molmet.2023.101801
Related findings · Hormonal
- Initial treatment for type 2 diabetes should be a combination of metformin and either an SGLT-2 inhibitor or a GLP-1 receptor agonist to achieve cardiorenal protection, rather than monotherapy or older agents like sulfonylureas.Strong
- For patients with specific monogenic obesity syndromes (leptin deficiency, POMC/PCSK1/LEPR mutations), targeted pharmacotherapy (recombinant leptin or setmelanotide) is highly effective and should be prioritized, unlike in polygenic obesity.Strong
- Continued weekly administration of 2.4 mg subcutaneous semaglutide prevents weight regain and promotes further weight loss in adults with overweight or obesity, whereas switching to placebo results in significant weight regain.Strong
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