Canagliflozin - Another Top Anti-aging Drug

What’s really interesting is that they used empagliflozin in this study, which (correct me if I’m wrong) is the most specific for SGLT2, so this suggests that the “off-target” target is NOT SGLT1.

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Confirmation that SGLT2i might protect the liver as well, at least in diabetic people: Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and dipeptidyl peptidase-4 inhibitors in improvement of fatty liver index in patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease: A retrospective nationwide claims database study in Japan 2024

This study aimed to evaluate the effectiveness of SGLT2i compared with that of dipeptidyl peptidase-4 inhibitors (DPP4i) in improving the fatty liver index (FLI) in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD).
SGLT2i showed a higher incidence of improvement in the FLI (≥30%, ≥40% and ≥50% reduction from baseline FLI) compared with DPP4i, and the weighted hazard ratios were 1.27 (95% CI 1.18-1.38), 1.24 (95% CI 1.13-1.37) and 1.19 (95% CI 1.05-1.33), respectively. SGLT2i indicated a greater decreased in FLI values compared with DPP4i at up to 3 years of the follow-up period.
SGLT2is use appeared to be associated with a greater improvement of the FLI than DPP4i use in patients with T2DM and MASLD.

The ongoing trials will tell us if SGLT2i also protect the liver of people without diabetes. :pray:

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Gout: one more indication for SGLT2i? See: Empagliflozin and Risk of Incident Gout: Analysis from the EMPagliflozin Comparative Effectiveness and SafEty (EMPRISE) Cohort Study 2024

Over a mean follow-up period of 8 months on treatment, the risk of gout was lower in patients initiating empagliflozin compared to DPP4i (HR = 0.69: 95% CI (0.60–0.79); RD = − 2.27: 95% CI (− 3.08, 1.46)) or GLP-1RA (HR = 0.83: 95% CI (0.73–0.94); RD = − 0.99: 95% CI (− 1.66, − 0.32)).

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study 2024

SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism.

No risk (or even small benefit) of taking SGLT2i if you suffer from asthma: Association of novel antihyperglycemic drugs versus metformin with decrease in asthma exacerbations 2024

While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

More evidence for combining GLP-1 RAs with SGLT2is? Combined sodium-glucose-transporters inhibitors and glucagon-like-peptide receptor agonist compared with monotherapy improves long-term survival: A Real-World Registry 2024

The combination therapy of sodium glucose cotransporter 2 inhibitor and glucagon like peptide 1 receptor agonist with respect to monotherapy reduces the risk of heart failure and all causes of mortality.

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis 2024

In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure.
Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

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Has anyone tried as low of a dose of Jardiance as 5mg? I’m taking 10mg and debating cutting in half.

I’m taking 6.25mg as that’s the dose which doesn’t drop my blood sugar too low when I take it in the morning.

Edit:
Based on this study Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Doses of Empagliflozin in Patients with Type 2 Diabetes Mellitus | Diabetes Therapy (springer.com) it appears that the difference in glucose reabsorption inhibition should not be significantly different between 6.25mg and 10mg, ranging at ~40% inhibition compared to placebo.

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Dr. Stanfied said he would consider adding 10mg Empagliflozin at the end here.

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Just saw the video myself. Given the data of empagliflozin’s effect on kidney and cardiovascular health, it seems like a no-brainer to add at this point.

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Agreed. I’ve been taking it for two years.

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Have you ever experienced low blood sugar on Jardiance?

No. I just had some labs and my fasted was 86. A1C 5.1. Fasting insulin 3.5

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I take the higher dose (25mg) of empagliflozin since it’s apparent that the potentially beneficial biologic effects aren’t provided strictly by glucose-lowering but by “off-target” effects; therefore, it may (or may not) be a faulty assumption that just because a half-dose works as well for glucose excretion, that it works just as well for everything else.

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10 mg was pretty much equivalent in terms of outcomes in the heart failure trial though.

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Yeah, I’m not sure if 25mg is better than 10mg, but I’m also 200 lbs (mostly lean mass), so I speculate that I may not get all the benefit of the 10mg dose that a smaller person might receive. I’m certainly open at any time to splitting the tabs in half to save money if I become solidly convinced that the 25mg dose is a waste.

At 12.5 mg, you’re getting 25% more than most people who start out at 10 mg. :wink:

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As canagliflozin reduced lifespan in female mice:

  1. Did clinical trials show such a gender effect for T2D, CKD, HF or any other condition?
  2. Does the remark mean females should use a lower dose?
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Checking this, it looks like indeed women might benefit less from SGLT2 than men:

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