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Fixed-dose combinations of oral GLP-1 RAs with other glucose-lowering agents in development are still a rarity, and this is the first GLP-1 plus SGLT2 in one tablet. HDM1010 tablets are a fixed-dose combination of an SGLT2 inhibitor and HDM1002, a potent, highly selective, orally active small-molecule GLP-1 receptor agonist — essentially an SGLT2/GLP-1 combo! https://lnkd.in/eHKg-crF…
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How unimolecular multi-agonists are compared with therapeutic cocktails of nutrient stimulated hormones? Metsera, now acquired by Pzifer, has introduced a concept of therapeutic NuSH cocktails, in which ultra-long-acting injectable GLP-1, GIP, glucagon, and amylin peptides are co-administered, in other words mixed and matches for personal needs (health risks, co-existing diseases, body weight target). Conceptually, Unimolecular…
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It’s intriguing to see the reintegration of pain signaling pathways into obesity therapeutics at a conceptual level.https://pilapharma.com/pilas-trpv1-asset/ PILA PHARMA is developing novel oral drugs for treatment of obesity and diabetes based on TRPV1 inhibition (XEN-D0501 is at a preclinical stage). TRPV1 (Transient Receptor Potential Vanilloid 1) is a non-selective cation channel, also known as the…
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A new review by Sebastián Zagmutt Caroca et al positions chronic hypothalamic microinflammation as an initiating event, not a downstream consequence, of systemic metabolic dysfunction and obesity: “The hypothalamus plays a central role in regulating energy balance, and its dysfunction is a key contributor to the development of metabolic diseases such as obesity and type…
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I have added 𝗺𝗲𝗻𝘁𝗮𝗹 𝗵𝗲𝗮𝗹𝘁𝗵 (brain) to the EASO’s framework of obesity management.It was a challenge to find space on this already busy diagram, and I may not have placed it perfectly—but I believe it deserves a more 𝗰𝗲𝗻𝘁𝗿𝗮𝗹 𝗽𝗼𝘀𝗶𝘁𝗶𝗼𝗻 in the diagram. One of the main challenges in integrating mental health into this framework…
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EASO and AACE combined These are the two most complementary infographics from the European Association for the Study of Obesity (EASO) and the American Association of Clinical Endocrinology (AACE). Both organisations have published updated guidance on the diagnosis and management of obesity in 2025, and there is substantial overlap between their frameworks. The key principles are repeated by EASO and…
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Organ cross-talk represents the complex reciprocal communication between distant organs mediated by various signaling factors. In other words, most of our organs are multilingual. This communication system involves cellular pathways, soluble mediators, and neurohormonal actions that maintain whole-body homeostasis. The foundational elements of inter-organ communication consist of closed-loop feedback mechanisms employing either stimulatory or inhibitory…
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When the Energy Balance Box Doesn’t Fit: Out-of-the-Box Thinking for Obesity. The energy imbalance simplification is wrong. Explaining obesity pathogenesis solely through the energy balance lens is a reductionist view. Plenty of publications have been written here on this topic, yet the final drop still hasn’t fallen to sink the energy imbalance theory of obesity.…
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FGF21 reverses MASH through coordinated actions on the CNS and liver – ScienceDirect When I combine these findings with the work of Prof. Brüning and his colleagues on the central regulation of the hypothalamus–liver axis (https://lnkd.in/embCm_9x), it gives the impression that FGF1 functions as a postprandial regulator of this axis. It appears to be secreted…