Hormonal
Once-weekly subcutaneous administration of the glucagon/GLP-1 receptor co-agonist NNC9204-1177 produces dose-dependent, clinically significant body weight loss in adults with overweight or obesity, but is associated with unacceptable safety concerns including increased heart rate, hepatic disturbances, and impaired glucose tolerance.
This specific drug (NNC9204-1177) is not available for clinical use because it caused unacceptable side effects like increased heart rate and liver issues, despite causing significant weight loss. However, it highlights that combining GLP-1 and glucagon pathways can lead to substantial weight loss, which is why other approved GLP-1 medications exist. If you are considering GLP-1 therapy, discuss the specific safety profile of the approved options with your healthcare provider.
Clinically relevant weight loss was achieved (up to 12.6% at week 12; 4,200 ug in the MAD trial), but this was not accompanied by cardiometabolic improvements. ... unacceptable safety concerns precluded further clinical development.
Why this rating
Phase 1 clinical trials (MAD, FHD/SAD, DDI) provide robust safety and PK data but lack long-term efficacy and large-scale comparative efficacy data.
Source
Glucagon/GLP-1 receptor co-agonist NNC9204-1177 reduced body weight in adults with overweight or obesity but was associated with safety issues
Martin Friedrichsen et al. · medRxiv · 2022
DOI 10.1101/2022.06.02.22275920
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