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Eric Topol analyzes:
When the Breakthrough Obesity G-Agonist Drugs Exceed Expectations
The expanding GLP-1 family of drugs and their expanded potential use cases
9/24
here's the summary:
Bottom Line
Despite some dizzying progress for this class of drugs, there are still so many unknowns (besides lack of explainability as already touched on). For example, why do people with diabetes lose less weight than obese, non-diabetics (first Figure from this post expanded to show the difference for the various drugs)?
For that matter, how precisely do these drugs work? As Aaron Carroll penned in a recent New York Times oped, like antidepressants, “medical treatments should not be dismissed just because we don’t fully grasp their mechanisms.” This lack of explainability (As Dr. Carroll wrote: “I’ve lost 15 pounds in the last five weeks, and I’ve done it with ease. It can’t just be because I’m eating much less, because I haven’t reduced my caloric intake that much. But like everyone else, including scientist, I have no idea why these drugs work so well.”) is akin to large language A.I. models like GPT-4—we really don’t know how they work. A critical point that Al Gore made in our recent podcast. (“We have no idea”).
Beyond these concerns, there’s now a family ranging from single to triple G-agonists and we have no idea how such potent interventions should be optimally used. More importantly, how can we get people taking these drugs weaned from them? It appears the drug manufacturers of G-agonists have no interest in this vital objective, without any ongoing prospective clinical trial efforts directed at cessation of their drugs without reversal of weight gain and assorted benefits. There is no reason to wonder about why this is the case, of course, but something has to be done.
I won’t again review here the issues of exorbitant costs, reimbursement coverage by insurers, health inequities, and lack of availability, since these were previously summarized.
The G-agonists are moving to become the most successful drugs in medical history, eclipsing other widely used and transformative drugs like statins. Their salutary and what appears to be marked impact— beyond losing weight— is getting validated in ways not fully anticipated, affecting cardiovascular outcomes, non-alcoholic fatty liver disease, and perhaps substance and behavioral addiction. In short, while there’s still so much that needs sorting out, we’ve got a breakthrough family of drugs that are already exceeding lofty expectations. Stay tuned!
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( How to tell the difference between alcoholic fatty liver and nonalcoholic fatty liver?
The fatty degeneration of liver cells occurs to a greater degree in NAFLD than in ALD. In contrast, inflammatory cell infiltration is more pronounced in ALD than in NAFLD. Furthermore, venous or perivenular fibrosis, phlebosclerosis, and (less commonly) lymphocytic phlebitis are more common in ALD than in NAFLD.) |
