#1266

You have to look at the normal trend with aging…

41598_2021_89442_Fig1_HTML

Distribution of estimated glomerular filtration rate and determinants of its age dependent loss

全文：Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study | Scientific Reports

2 Likes
#1267

And what’s the trend like with genetic SGLT2 inhibition? Do they have immortal kidneys?

1 Like
#1268

All I have to go on is the @adssx paper, it should halt the decrease at whatever age you start…

  • SGLT2 prevent eGFR decline across the board (RCTs + MR + association studies)
  • Cherry on the cake: SGLT2i increases longevity in males (MR + mice studies)
1 Like
#1269

I’ll wait for a graph if someone finds it. If genetic SGLT2 inhibition gives immortal kidneys. Like genetic LDL lowering gives immortal hearts.

1 Like
#1270

I read papers for myself as a man so I might miss or forgot information related to females. But from what I remember:

  • Dapagliflozin and empagliflozin are approved for CKD, HF and T2D (canagliflozin is approved for T2D but not for HF and CKD without T2D), in men and women. I don’t think trials showed differences in outcomes by gender. Guidelines and clinical practice don’t seem to differ by gender either.
  • Women are more prone to UTI and genital infections in general. So their risk is even higher on SGLT2 (even though the OR might be the same as men, their baseline risk is higher).
  • Besides the ITP, the Mendelian randomization found that SGLT2 inhibition was causally associated with longevity in males (father’s attained age) but I don’t know if they looked at females (or if the result was negative?).
  • I think the ITP team said that the lack of benefits in female rodents might be a dose issue and they’re now trying a lower dose (60 ppm vs 180 ppm, both at 7 mo).
4 Likes
#1271

What are you saying? We have RCTs, so of course it’s clinically relevant.

That being said, I don’t know if the step is 1 SD or a per-allele increase and if 0.05 means 5% increase in eGFR. I’m not knowledgeable enough and ChatGPT (o1) tells me the paper isn’t clear on that…

#1272

I’ll be waiting for more research then.

#1273

Yes they do, look at these OR: Mendelian randomization study of sodium–glucose cotransporter 2 inhibitors in cardiac and renal diseases 2024

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MR analysis suggested that SGLT2i can provide substantial protection against a variety of CKD (Figure 3, Supplementary Table 3). Significant protection effects were observed for nephrotic syndrome (OR 0.0011, 95% confidence interval [CI] 0.000–0.237, P = 0.013), chronic glomerulonephritis (OR 0.0002, 95% CI 0.000–0.210, P = 0.017), and hypertensive nephropathy (OR 0.0003, 95% CI 0.000–0.785, P = 0.043).

2 Likes
#1274

That’s a kidney disease I know nothing about. keeping eGFR in youthful range through someone’s entire life would be more significant.

#1275

Damn check the image… :man_facepalming:

#1276

In the image there’s three kidney diseases that are significant I know nothing about, it doesn’t change anything, we were talking about eGFR.

#1277

By the way, @AnUser, do we have MR studies for HMGCR and atherosclerosis? What’s the OR per 1 SD? (I couldn’t find after a quick search)

#1278

Variants in PCSK9 and HMGCR were associated with nearly identical protective effects on the risk of cardiovascular events per decrease of 10 mg per deciliter (0.26 mmol per liter) in the LDL cholesterol level: odds ratio for cardiovascular events, 0.81 (95% confidence interval [CI], 0.74 to 0.89) for PCSK9 and 0.81 (95% CI, 0.72 to 0.90) for HMGCR. …

https://www.nejm.org/doi/10.1056/NEJMoa1604304

About 0.58 per 1 SD decrease in LDL.

#1279

I’m not sure that’s what we want. Here it says “if you lower your LDL by 10 mg/dL thanks to a PCSK9 or HMGCR variant then…”. What we want is the effect of HMGCR on LDL (which is the analogy of SGLT2<>eGFR that you’re asking for).

#1280

That doesn’t make sense to me, as eGFR is the outcome, not the way to measure amount of SGLT2 inhibition, like LDL is for HMGCR or PCSK9. It measures kidney function. Or am I missing something here?

#1281

Very insightful: thanks you very much!

1 Like
#1282

OK - I’m checking into the cost for all the work I need to do to upgrade my associated software plugins so that everything works with the latest version. Its not as simple as I wish it was, since I self-host this software with a unique software set.

4 Likes
#1283

Very few people will use it I think, and even if they would they wouldn’t learn enough… Peter Attia never starts anyone on rapamycin without them spending a lot of effort learning themselves about the topic. Low expected value.

It all comes down to new original research every day of the week, anyway. That will be boosted into new threads anyway which aren’t super long, I think. It’s better to be realistic and not hype into tech.

#1284

I live in the Silicon Valley and work in tech… leaning into the tech adoption curve is what we do here… if for no other reason than to learn about it and see how well it works :wink:

5 Likes
#1285

Wait until AI agents are here, then you can just have a Genie AI agent you implement on the forum you can ask anything about the content (and it can find it). That’s where all of this seems to be going anyway… It doesn’t even have to be hosted in the same place (just can browse like any of us).