#279 - AMA #53: Metabolic health & pharmacologic interventions: SGLT-2 inhibitors, metformin, GLP-1 agonists, and the impact of statins
Peter Attia discusses pharmacologic tools for metabolic health and diabetes, including SGLT-2 inhibitors, metformin, and GLP-1 agonists. He also explores the relationship between statin use and insulin resistance/type 2 diabetes.
Deep Dive Analysis
8 Topic Outline
Introduction to AMA 53: Metabolic Health and Statins
Pharmacologic Tools for Metabolic Health: SGLT2 Inhibitors
Understanding the Nephron and Kidney Filtration
Mechanism of Action: How SGLT2 Inhibitors Work
Historical Development of SGLT2 Inhibitors from Phlorizin
Comparing FDA-Approved SGLT2 Inhibitors and Their Efficacy
Benefits of SGLT2 Inhibitors Beyond Glycemic Control
SGLT2 Inhibitors as Potential Geroprotective Molecules
3 Key Concepts
Nephron
The nephron is the functional cellular unit of the kidney responsible for filtration. It works by initially dumping everything from the blood (glucose, sodium, etc.) and then selectively reabsorbing only what the body needs back into circulation.
SGLT2 Inhibitors
SGLT2 inhibitors are a class of drugs that block the sodium-glucose co-transporter protein 2 in the kidney's proximal tubule. By blocking this protein, they prevent the reabsorption of sodium and glucose, causing more of both to be excreted in the urine, thereby lowering blood glucose levels.
Phlorizin
Phlorizin is a naturally occurring chemical found primarily in apples and other fruits, which was historically observed to induce glucosuria (glucose in urine). This natural compound served as the impetus for the development of modern SGLT2 inhibitor drugs.
5 Questions Answered
SGLT2 inhibitors are drugs that block the sodium-glucose co-transporter protein 2 in the kidney, preventing the reabsorption of glucose and sodium, leading to their excretion in urine and thus lowering blood glucose.
They were developed based on the observation that phlorizin, a naturally occurring compound found in apples, caused glucosuria (glucose in urine), leading scientists to investigate and synthesize molecules that could mimic this effect.
The four FDA-approved SGLT2 inhibitors are canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin, all of which share a similar chemical structure but differ in potency and dosing.
Drug companies deliberately create complex generic names so that doctors and patients will associate the drug with its easier-to-remember brand name, which is proprietary and can lead to longer sales after the generic version is available.
Beyond lowering blood glucose, SGLT2 inhibitors have been shown to reduce blood pressure and decrease the risk of hospitalization and death for heart failure patients, even in those without type 2 diabetes.
2 Actionable Insights
1. Optimize Cellular Hydration
To optimize for water movement and cellular hydration, consume mixtures of glucose and sodium, as they are the best ways to hydrate cells and move together very efficiently.
2. Watch Podcast Video
Subscribers can watch the full video of this podcast on the show notes page, while non-subscribers can view a sneak peek on the YouTube page.
3 Key Quotes
the kidney has one way of filtering which is it goes to the dresser and takes every single thing out and then it simply pulls back in what it wants to keep.
Peter Attia
if you had a way to block that purple thing you would be able to keep more glucose in the urine.
Peter Attia
it's just classic pharma chicanery which is let's make sure that doctors and patients alike are associating the brand name with it and presumably there's some belief that that translates to a longer tail of sales.
Peter Attia