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Peter Attia MDMetabolic health & pharmacologic interventions: SGLT-2 inhibitors, metformin (AMA 53 sneak peek)
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At a glance
WHAT IT’S REALLY ABOUT
How SGLT-2 Inhibitors Work and Why Scientists Find Them Promising
- Attia uses a dresser-cleaning analogy to explain that the kidney filters everything out of plasma and then selectively reabsorbs what the body needs, which creates an opening to block glucose reabsorption.
- SGLT2 inhibitors block the sodium-glucose co-transporter so the body excretes more glucose and sodium in urine, offering a glucose-lowering strategy for type 2 diabetes.
- The drug class descends from phlorizine, a compound found in apples that caused glucose in the urine of non-diabetic people, and four approved '-flozin' drugs now exist, with canagliflozin having the most data.
- Attia says canagliflozin lowers A1c by about 0.7 to 1% alone and by an average of 1.8% when combined with metformin, and he also notes blood pressure reductions.
- Attia says scientists see more promise in SGLT2 inhibitors than the public does, citing Interventions Testing Program findings and cardiovascular benefits in heart failure patients with or without diabetes; the geroprotective discussion is cut off by the sneak peek.
IDEAS WORTH REMEMBERING
5 ideasThe kidney filters by removing everything and reabsorbing what it needs.
Attia says this design means the kidney only has to recognize a finite set of good things, which is why blocking glucose reabsorption is possible.
Blocking SGLT2 makes the body excrete glucose and sodium.
Preventing reabsorption in the proximal tubule means more glucose and sodium leave in the urine, lowering blood glucose in type 2 diabetes.
SGLT2 inhibitors were derived from a natural compound.
Phlorizine from apples induced glucose in the urine of non-diabetic people, hinting at the pathway; Attia notes metformin, statins and rapamycin are also naturally derived.
Combining canagliflozin with metformin produces a large A1c drop.
Attia cites 0.7 to 1% absolute A1c reduction for canagliflozin alone and an average 1.8% with metformin, versus up to 1.3% for metformin monotherapy.
The benefits may extend beyond glucose control.
Attia notes weight loss and lower blood pressure, and says heart failure patients do better on SGLT2 inhibitors even without type 2 diabetes.
WORDS WORTH SAVING
5 quotesThe 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
We come up with really, really bad acronyms.
— Peter Attia
The public is way more interested about metformin. I think the scientific community sees much more promise in SGLT2 inhibitors, at least on average, and that's based on my very unofficial survey of this.
— Peter Attia
It's just, you know, classic pharma chicanery, which is let's make sure that doctors and patients alike are associating the brand name with it
— Peter Attia
It is really interesting that nature's kind of given pharmacologists a head start on drug development in many cases.
— Peter Attia
High quality AI-generated summary created from speaker-labeled transcript.
