With such a large patient target population that will benefit from these G-agonists, they should be on the list of drugs requiring price negotiation by Medicare. Second, with funds from multiple NIH Institutes, research should be encouraged into the gut-brain connection affected by these drugs. Perhaps, this research may provide insights into how to wean patients from these drugs without losing all their benefits.
Sep 24, 2023·edited Sep 25, 2023Liked by Eric Topol
SUPERB ARTICLE ERIC : MECHANISMS ARE THE CHERRY ON THE CAKE, NOT NECESSARY IMMEDIATELY, BUT ESSENTIAL IN FUTURE TO ADVANCE THE SCIENCE. FOR IMMEDIATE MEDICAL APPLICATION, WELL EXECUTED AND WELL DESIGNED CLINICAL TRIALS WILL DO NICELY FOR NOW. ANYWAY, ONE DID NOT NEED TO KNOW THAT THE EARTH REVOLVES AROUND THE SUN OR EVEN DISMISS THE THEORY THAT THE SON GOD RODE HIS CHARIOT ACROSS THE SKY FROM DAWN TO DUSK, TO KNOW HOW TO USE THE SUNS SHADOW TO DETERMINE WHEN TO PLANT AND HARVEST CROPS...THE REALLY INTRIGUING THING FOR ME AS A CARDIOVASCULAR SPECIALIST, IS THE POSSIBILITY FOR LONG TERM MODIFICATION OF DELETERIOUS PERSONAL HABITS THAT IMPINGE ON HEALTH, SIMULTANEOUSLY ACHIEVING METABOLIC MODIFICATION. THE BRAIN EFFECTS ARE TRULY AMAZING. I TAKE SEMAGLUTIDE AND I CAN TELL YOU THE CARB AND SUGAR AND EVEN ALCOHOL CRAVINGS ARE MASSIVELY REDUCED. THAT SAID LONG TERM EFFECTS AND WEANING ARE SO IMPORTANT TO UNDERSTAND AS YOU ELEGANTLY POINT OUT. PERHAPS THE RECEPTORS IN THE BRAIN INCREASE IN SENSITIVITY OR NUMBER AS WE LOSE WEIGHT ON THESE DRUGS --JUST LIKE WITH DIABETES....
Thank you for mentioning Svetlana Mojsov and referencing Rosalind Franklin. Sounds all too familiar in sprite of Doudna and Charpentier and Kariko. Recognizing this problem in science is as important as the new drugs if we hope to have a future of continued progress. One wonders if Mosjov's work had been given greater attention in 1986 these "new" drugs would have been available to us decades ago - as was the case with CRISPR and mRNA vaccines.
We are living in very exciting times. Two industrial revolutions running in tandem with unlimited potentials for improving and transforming our condition. VCs are living in a target-rich envirinment and I foresee the pace of major discoveries accelerating. If we can just stay out of any big wars that is.
This is a great summary, but I would take exception to one of your descriptions: "A subgroup analysis by weight reduction iced the case for proportionate benefit of symptom relief and less inflammation (by biomarkers) as a function of weight loss". The test for trends is something of a statistical illusion. There is clearly a difference between <5% and >5% but there is much less of a difference among those with >5%, especially for change in exercise function. It is the former that is driving statistical significance. You see a similar effect when analyzing dose-response in fixed dosage placebo-controlled studies that include the placebo arm as a dosage of zero. The statistical significance is driven by the difference between drug and placebo. To truly establish dose/response you must exclude the placebo group. In this case, instead of proportion to weight loss you may have more of a responder/non-responder effect where weight loss and exercise function (or KCCQ-CSS improvement) are coincident effects or a threshold effect where these effects are caused by a >5% decrease in weight but are affected less, if at all, by further weight loss.
Dr. Topol - Belatedly read this post when writing a draft research proposal with UNC School of Medicine and incorporated a quotation from it. Our proposal for a step-down medical food to complement the GLP-1RA injections argues from 20 years of research data that it is possible to formulate a medical food that will produce systemic GLP-1 and PYY levels comparable to Roux-en-y gastric bypass, at a half-life about 15-20% of the injection levels. Our concept has been reviewed and is supported by Dr. John Buse at UNC, a veritable guru in this area of endocrinology. Your words support the medical need for such a solution as we propose and have capability to make. Is there a way to send you the research draft for your thoughts? Edison Hudson - Chapel Hill, NC edison@oneful.health
It will not surprise anyone who follows big Phrma that the US is the ONLY country where these drugs are extremely expensive. USA= $936. Second most expensive is Japan at $169. https://www.healthsystemtracker.org/brief/prices-of-drugs-for-weight-loss-in-the-us-and-peer-nations/
With such a large patient target population that will benefit from these G-agonists, they should be on the list of drugs requiring price negotiation by Medicare. Second, with funds from multiple NIH Institutes, research should be encouraged into the gut-brain connection affected by these drugs. Perhaps, this research may provide insights into how to wean patients from these drugs without losing all their benefits.
Agree!
SUPERB ARTICLE ERIC : MECHANISMS ARE THE CHERRY ON THE CAKE, NOT NECESSARY IMMEDIATELY, BUT ESSENTIAL IN FUTURE TO ADVANCE THE SCIENCE. FOR IMMEDIATE MEDICAL APPLICATION, WELL EXECUTED AND WELL DESIGNED CLINICAL TRIALS WILL DO NICELY FOR NOW. ANYWAY, ONE DID NOT NEED TO KNOW THAT THE EARTH REVOLVES AROUND THE SUN OR EVEN DISMISS THE THEORY THAT THE SON GOD RODE HIS CHARIOT ACROSS THE SKY FROM DAWN TO DUSK, TO KNOW HOW TO USE THE SUNS SHADOW TO DETERMINE WHEN TO PLANT AND HARVEST CROPS...THE REALLY INTRIGUING THING FOR ME AS A CARDIOVASCULAR SPECIALIST, IS THE POSSIBILITY FOR LONG TERM MODIFICATION OF DELETERIOUS PERSONAL HABITS THAT IMPINGE ON HEALTH, SIMULTANEOUSLY ACHIEVING METABOLIC MODIFICATION. THE BRAIN EFFECTS ARE TRULY AMAZING. I TAKE SEMAGLUTIDE AND I CAN TELL YOU THE CARB AND SUGAR AND EVEN ALCOHOL CRAVINGS ARE MASSIVELY REDUCED. THAT SAID LONG TERM EFFECTS AND WEANING ARE SO IMPORTANT TO UNDERSTAND AS YOU ELEGANTLY POINT OUT. PERHAPS THE RECEPTORS IN THE BRAIN INCREASE IN SENSITIVITY OR NUMBER AS WE LOSE WEIGHT ON THESE DRUGS --JUST LIKE WITH DIABETES....
Thank you for mentioning Svetlana Mojsov and referencing Rosalind Franklin. Sounds all too familiar in sprite of Doudna and Charpentier and Kariko. Recognizing this problem in science is as important as the new drugs if we hope to have a future of continued progress. One wonders if Mosjov's work had been given greater attention in 1986 these "new" drugs would have been available to us decades ago - as was the case with CRISPR and mRNA vaccines.
Thank you for this incredibly informative review!! Sadly, according to the drug makers, there is no end in sight to the supply shortages.
We are living in very exciting times. Two industrial revolutions running in tandem with unlimited potentials for improving and transforming our condition. VCs are living in a target-rich envirinment and I foresee the pace of major discoveries accelerating. If we can just stay out of any big wars that is.
This is a great summary, but I would take exception to one of your descriptions: "A subgroup analysis by weight reduction iced the case for proportionate benefit of symptom relief and less inflammation (by biomarkers) as a function of weight loss". The test for trends is something of a statistical illusion. There is clearly a difference between <5% and >5% but there is much less of a difference among those with >5%, especially for change in exercise function. It is the former that is driving statistical significance. You see a similar effect when analyzing dose-response in fixed dosage placebo-controlled studies that include the placebo arm as a dosage of zero. The statistical significance is driven by the difference between drug and placebo. To truly establish dose/response you must exclude the placebo group. In this case, instead of proportion to weight loss you may have more of a responder/non-responder effect where weight loss and exercise function (or KCCQ-CSS improvement) are coincident effects or a threshold effect where these effects are caused by a >5% decrease in weight but are affected less, if at all, by further weight loss.
Dr. Topol - Belatedly read this post when writing a draft research proposal with UNC School of Medicine and incorporated a quotation from it. Our proposal for a step-down medical food to complement the GLP-1RA injections argues from 20 years of research data that it is possible to formulate a medical food that will produce systemic GLP-1 and PYY levels comparable to Roux-en-y gastric bypass, at a half-life about 15-20% of the injection levels. Our concept has been reviewed and is supported by Dr. John Buse at UNC, a veritable guru in this area of endocrinology. Your words support the medical need for such a solution as we propose and have capability to make. Is there a way to send you the research draft for your thoughts? Edison Hudson - Chapel Hill, NC edison@oneful.health