I have a doctor in Hong Kong who will prescribe any drug I ask him for. They do exist.
I have a cadre of doctors that I see for various different circumstances. Each has a different specialty. I don’t know what I’d do if I only had one doctor. I don’t think only one could meet all my needs.
Canagliflozin is associated with a clinically meaningful reduction in hemoglobin A1c (HbA1c) for children and adolescents with type 2 diabetes mellitus (T2DM), according to a study published online Aug. 5 in the Annals of Internal Medicine .
Ulhas Nadgir, M.D., from Sutter Medical Group in Sacramento, California, and colleagues assessed the safety and efficacy of canagliflozin in children and adolescents aged 10 years or older with T2DM in a phase 3 randomized, placebo-controlled multicenter study conducted in 104 sites in 10 countries. Participants were randomly assigned to canagliflozin (100 mg) or placebo once daily (84 and 87 individuals, respectively); at week 13, participants with week 12 readings of 7 percent or higher for HbA1c and at least 60 mL/min/1.73 m2 for estimated glomerular filtration rate were randomly assigned to continue receiving 100 mg canagliflozin (or placebo) or to have their dose uptitrated to 300 mg (or placebo).
I’m about 2 weeks in w/ 10mg Jardiance and no side-effects so far. I expected perhaps increased urination and/or fatigue, but neither of these has happened. My urinary system actually seems to be functioning more smoothly and I think I’ve actually been urinating less. I did use amphetamine for a week or so during this time, which normally is a strong diuretic for me, during which I also seemed to be urinating less. I think I’ve felt a bit sharper and better mood on average too.
Very pleased that I’m responding well to it, as I might be able to tolerate an even higher dose. I think empa currently has the best evidence as LS extension drug in humans (yes, even better than rapa), and especially shoutout to @adssx for compiling so much of this data in humans here. This is not only factoring in the protection across multiple organ systems (e.g heart, brain, liver, & kidney),but also the protection against multiple pathological aging processes like fibrosis & cancer. The lowering of A1C, while I doubt is what’s primarily mediating these effects, is just icing on the cake.
The anti-fibrotic effects would potentially represent a bona fide anti-aging mechanism, as fibrosis is a tissue/organ-level manifestation of cellular ‘mesenchymal drift/MD’, which appears to have some universality across numerous cell types and tissues in both aging and disease, with MD intensity correlating with mortality. In particular, it seems that SGLT2i might exert their anti-fibrotic effects via modulation of the Hippo signaling pathway, which plays an autoregulatory role in fibrosis, although it’s not clear the proximal manner in which they interact w/ this pathway.
Highly recommend everyone check out this paper just published in Cell (had to delete some of the data only pages, as well as experimental section, refs and supplemental in order to fit):
Prevalent mesenchymal drift in aging and disease is reversed by partial reprogramming.pdf (6.7 MB)
As they mention, it still remains to be proven whether this MD drift is causally contributing to diseases/aging, but there are a number of results which point in this direction.
So do supermodels, but I’ve never dated one. 
I’d gladly trade my Doc for a supermodel though.
Chinese MR, Fuzhou University (okay-ish?): Two Birds With One Stone: The Protective Role of the Antidiabetic Drug Sodium-Glucose Cotransporter-2 Inhibitor in Neurodegenerative Diseases 2025
The neuroprotective role of sodium-glucose cotransporter-2 inhibitor (SGLT2i) has attracted considerable interest. The purpose of this study was to investigate the role of SGLT2i in several common neurodegenerative diseases (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Utilizing drug-target Mendelian randomization (MR) and colocalization, we used single nucleotide polymorphisms (SNPs) proximal to the SLC5A2 gene to analyze the influence of SGLT2i on AD, PD, ALS, and MS. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Phenome-wide association study (PheWAS) was used to probe the relationship of SGLT2i with other characteristics. Protein–protein interaction (PPI) networks were used to explore how SLC5A2 affects other proteins, and enrichment analysis was used to explore possible biological processes. The MR analysis showed that SGLT2i was negatively associated with AD (OR = 0.77, p = 0.01), PD (OR = 0.52, p = 0.04), ALS (OR = 0.60, p = 0.01), and MS (OR = 0.33, p = 0.027), indicating that SGLT2i could reduce the risk of AD by 23%, PD by 48%, ALS by 40%, and MS by 67%. The colocalization supported this conclusion. The PheWAS showed that SGLT2i was associated with body mass index and systolic blood pressure. SGLT2i is biologically closely related to the development of NDs. This study suggested that SGLT2i was able to reduce the risk of NDs. SGLT2i may perform this process through many mechanisms. This study provides a new perspective on the treatment of NDs; clinical trials and relevant experiments are necessary to further validate the neuroprotective effects of SGLT2i.
Amen 
(poke @DrFraser )
It is interesting on the neurocognitive decline side of things first for AD then for PD what some of the data shows:
Then with Vera-Health - their discussion on PD - which needs to be updated based upon this article.
In contrast, SGLT2 inhibitors show cognitive protection benefits in dementia/Alzheimer’s risk reduction 7, 8, but no convincing evidence exists yet for a direct protective effect on Parkinson’s disease development.
I try to have all my neurocognitive decline risk patients on both - but some don’t have the ability to, for cost or due to not having body weight to lose and risk of sarcopenia with pushing things. I’d like to see a bit more on PD in this space before prioritizing SGLT-2i over GLP-1’s … it would however seem very sensible, if no contraindication to run both simultaneously, which is what I try to do. For those who are already lean, I usually get away with full dose SGLT2’s without too much weight loss.
This is outdated: the phase 3 trial of exenatide failed in PD: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02808-3/fulltext
Great to hear. Are you planning on increasing from 10mg to 25mg? Why or why not? Just curious because you seem thoughtful about your interventions and I’ve been going back and forth re whether to increase the dose.
Hi All, Much tnx to such fine data/discussion as always. Bought Dapa from India (same person we all use for cheap so not married to my stash).
Empa vs Cana vs Dapa vs? I did a google some time ago and guessed Dapa had fewer side effects may have been wrong.
Admin here moved to Empa, probably for good reasons (hopefully other then possible cost?).
I have alternated taking 5mg Dap (10mg split) both / alternating with 250mg metformin at night. Night to attampt to avoid the possible fatigue and mainly to benefit from thymus gland rejuvination.
As tipped by rejuvination health coach Alex Kikel (search on youtube).
Rethinking my fatigue test maybe I need to test taking metformin at noon after feeling perky in the AM to see if I roll over. Then same experiment with dapa at noon. I was taking dapa early AM in a blender (can’t swallow pills).
I eat very low carb so I may be teasing my body with night / day hypoglycemic events un-wittingly. I need to find my lost CGM stash.
Mainly any terse summry of this wise groups preference for which SGLT2 without regard to cost or difficulty getting, assuming some lower dose since I’m low carb, zero fruit, only for anti aging.
Best to all, curt
Empagliflozin Improves Insulin Sensitivity of the Hypothalamus in Humans With Prediabetes: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial
“Our results corroborate insulin resistance of the hypothalamus in humans with prediabetes. Treatment with empagliflozin for 8 weeks was able to restore hypothalamic insulin sensitivity, a favorable response that could contribute to the beneficial effects of SGLT2 inhibitors. Our findings position SGLT2 inhibition as the first pharmacological approach to reverse brain insulin resistance, with potential benefits for adiposity and whole-body metabolism.”
In MICE.
Empagliflozin decreases ageing-associated arterial stiffening and vascular fibrosis under normoglycemic conditions
https://www.sciencedirect.com/science/article/pii/S1537189123000721
One more longitudinal study: https://www.sciencedirect.com/science/article/pii/S0168822725004449
SGLT2 inhibitor use was associated with a 20 % lower risk of all-cause dementia compared to DPP-4 inhibitors.
Strongest effects observed in patients >80 years and male patients.
SGLT2i showed a significant reduction in unspecified dementia but not in Alzheimer’s or vascular dementia.
FWIW, my hematocrit numbers went up - possibly due to empa?
Possible Mechanism of Hematocrit Elevation by Sodium Glucose Cotransporter 2 Inhibitors and Associated Beneficial Renal and Cardiovascular Effects
https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.118.038881
Yes, almost certainly the reason. Not a problem unless high (maybe over 52 or 54?) although cutoff isn’t clear, and maybe even then not much of a problem unless there are other risk factors for arterial/venous thrombosis. And it can certainly be a positive if hematocrit is too low.
I’m at 48.2 - according to LabCorp, it’s still within their reference interval 37.5 - 51, so I figure as long as I keep adequately hydrated I should be fine.
You are golden at 48. My most recent was 53, so I stopped empagliflozin for the time being. If normalized, I’ll start back on a 1/2 dose of dapagliflozin, since unlike empa its Hct-raising property is dose-dependent.
A perk to stopping empagliflozin is only having to get up once at night to pee instead of 2 or 3(!). I’ll definitely have to weigh the sleep impairment against the potential health benefits in deciding whether to continue using an SGLT2i long-term.
Exactly the reason I have half a drawer of empag left and just bought more Dapag. No side effects and I even take the high dose of Forxega.
Do you think it could be safe to take mirabegron to reduce awakenings and also burn fat at the same time? Or is it harmful to keep the glucose-enriched urine in the bladder?