It had zero to do with cost. I have a memory like a sieve, so I’ll see if I can find it today and circle back …
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I quickly found this in the FAQs
At Healthspan, we recommend a conservative and gradual approach to oral dosing. Most individuals begin at 5 mg per day, taken 5 days per week (with 2 days off). This intermittent protocol helps activate methylene blue’s benefits while reducing the risk of overexposure or tolerance.
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Got it, for some reason I thought you were talking about empaglifozin, not methylene blue.
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You have to meet your deductible to have any meds covered by your insurance? That’s insane.
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@PrimarchLongevity Wanna hear something even more criminal? This year, for the first time, I added up what I pay each month at the pharmacy with my insurance ‘negotiated rate’ and compared that to buying a year’s worth with good rx cash pay… buying it on my own without the help of insurance saved me well over 1k!
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I’ve had good luck with manufacturer coupons for other drugs in the past.so people should definitely give that a try.
The trick for me has been finding a doctor who will prescribe it to someone with excellent insulin sensitivity. Some anti-aging/longevity docs will, but they are few and far between and are expensive, which partially defeats the purpose (at least you get a script). I can’t even get a doc to prescribe cholesterol medications.
[Yes, @Agetron has the perfect doctor who essentially hands over the prescription pad at every visit, but that doctor is a 
. 
]
My experience is that I’m basically told to come back when I’m fat and sick with arteries coated in bacon grease and then they’ll help me.
So it’s India or pay a telemedicine place with a slick website a small fortune for what would otherwise be cheap medications.
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Sometimes I make the mistake of looking at Mark Cuban’s CostPlusDrugs prices after filling a prescription at the drug store. Definitely don’t do that.
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Good news for those considering taking empagliflozin concurrently with pioglitazone:
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I was under the impression that empagliflozin, unlike canagliflozin, didn’t affect mTOR. Perhaps I should switch back, but I had nocturia issues my first try.
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Hahaha - working at a medical university for 25 years, you develop long relationships with many future physicians. Yes, I was lucky that one I knew best stayed in town. Only went to him after my previous 3 physicians over a decade were of no help. Their attitude on TRT, or rapamycin was stay the course - you are going to get old - live with it. Felt pretty hopeless - I even used the expensive online docs for a bit. But, they only would give a month prescription at a time, and everytime you end up with a new doc and constant visits for another month of prescription was expensive in the long run.
My curent GP is fantastic, as long as I can provide current research showing potential - he is willing to monitor me and provide the opportunity to test it out. Most of these medications have been given out for a decade with no issues. The struggle to be responsible for your health is almost impossible with most physicians in this litigious society. You almost have to have more than a patient relationship to move that needle.
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I also have such a PCP like @Agetron! The trick is to shop for one who has positive reviews in the listening department, and isn’t a narcissistic know-it-all.
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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.
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Canagliflozin Tied to Reduction in HbA1c in Children, Teens With T2DM
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).
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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.
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So do supermodels, but I’ve never dated one. 
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I’d gladly trade my Doc for a supermodel though.
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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 )
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It is interesting on the neurocognitive decline side of things first for AD then for PD what some of the data shows:
- Large target trial emulation (396,963 patients): Both GLP-1RAs (HR 0.67; 95% CI 0.47–0.96) and SGLT2 inhibitors (HR 0.57; 95% CI 0.43–0.75) were independently associated with lower risk of Alzheimer’s disease and related dementias (ADRD), but no difference was seen between the two classes (HR 0.97; 95% CI 0.72–1.32) (Level II evidence, JAMA Neurology 2025) 2.
- Meta-analysis of observational cohorts (27 studies, >50,000 patients, 2023): Both SGLT2i (OR 0.41 [95% CI 0.22–0.76]) and GLP-1RA (OR 0.34 [95% CI 0.14–0.85]) were associated with reduced dementia risk, ranking nearly identical in efficacy (SUCRA: SGLT2i 94.4%, GLP-1RA 92.7%) II 3.
Then with Vera-Health - their discussion on PD - which needs to be updated based upon this article.
- A large cohort study (~100,000 patients with diabetes) in Brain demonstrated a significantly lower risk of incident PD in patients using GLP-1 mimetics (and DPP-4 inhibitors) compared with other glucose-lowering drugs 1 II.
- A systematic review and meta-analysis of 10 studies (Frontiers in Neurology, 2021) found GLP-1 agonists reduced PD risk by ~59% (HR 0.41, 95% CI 0.19–0.87, p=0.02), while evidence for SGLT2 inhibitors and other agents was absent or non-significant 2 I.
- Randomized controlled trials in PD patients (Exenatide, Lixisenatide, NEJM/Lancet) demonstrated improvements in motor function and slower disease progression beyond glycemic control, supporting a disease-modifying role of GLP-1 agonists 3, 4 I.
- Multiple mechanistic studies suggest GLP-1 agonists act via enhanced brain insulin signaling and neuroprotection 5, 6 (preclinical & translational).
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.
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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
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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.
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