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I have a general question about SGLT2i, metformin, and Lipid lowering meds (Ezetimibe, PITA, etc). Is it a ok to take them every other day as opposed to daily? or maybe anywhere from 2-3 days per week or they must be taken daily? I am talking for those of us that take them for longevity purposes only and have our markers in the normal/optimal range.
Reason I ask is because I do trial and error sometimes (especially if I’m feeling not my best, I just stop everything/most meds for 2-4 days) and then I feel great. and that great feeling tends to stay with me even when I start taking meds again for a while, say two weeks or so. Now, I’m not necessarily blaming meds for the time I may not be feeling best (could be other things also, i.e. lack of sleep, weather, cold symptoms etc…)
Has anyone come across research or suggestions (from the longevity docs) that might be a good idea to take these meds more sparingly as opposed to daily?
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If you’re doing trial and error to find out what works for you, you’re better off taking something for a block of time and then not taking it for a block of time and noting differences. Repeat it a few times and you’ll see what is working and what is not.
You absolutely can take things on and off. I take SGTL2i 4 days in a row and take a 3 day break. This is to prevent urinary infection and excess urination (I find that annoying).
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I hear you but what works best for me (meaning the way I may feel) may not be best for longevity purposes, and that is my dilemma. I’ll have to do more research in terms of med’s 1/2 life and mechanisms of action etc… to try and come up with a more educated answer/approach. I might play around a bit. At moment thinking of doing glucose lowering ones (ACA, Metformin and SGTL2i on RAPA day and 2-3 days after and stop them for the rest of the week or maybe stick with only one and stop the other two, and probably do the same with the lipid lowering ones.
Playing with doses and regimens is probably best done by people who have access to frequent doc checkups and frequent lab work so they can measure the results to try and find the sweet spot. For most of us (including me) that do checkups annually we might be shooting in the dark (without data to look into).
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Like you, I find myself doing ad hoc cycling plus some that is slightly more evidence based. I can appreciate that some of us might want to develop and adhere to a more strict cycling calendar; however, for most of the geroprotective substances we are experimenting with, almost any such calendar invokes a degree of misplaced confidence. We find this kind of misplaced confidence amusing when we observe a non-scientist reporting the mean of a handful of +/- 20% estimates out to three decimal places. Not much different in this realm. Exceptions would obtain if you are taking precision measurements and following a rigorous methodology, which is a great thing to do if you have the interest. I find that I lack that level of interest i this area of life.
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I take my statin and some supplements every other day to avoid side effects. Just realize that taking a prescription drug every other day lessens it’s effectiveness but may also reduce side effects.
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I imagine you’ve seen the thread on this, but incase you haven’t, Good labs is a site where you can request dirt cheap labs on your own, with no doc involvement. Their AI will even analyze them for you (not that you need that part). Also, in NY, if you donate blood, many of their labs will be free (I imagine you just tack on the additional ones you might want).
For your first order you can get 20% off with a code… I have one or I’m sure many others do as well.
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Thanks, and yes, I use Goodlabs thanks to someone that suggested it on this website. Was using LabCorp but they are easily 30% more expensive.
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Great… and here is a helpful hint because I was just ordering labs for my brother in DC… check Labcorp against Quest, even when purchasing them within Good Labs.
I use Quest here, and when I was ordering labs for him at Labcorp through Good Labs, I was shocked at some of the prices, so I then compared those to using Quest and it was vastly less expensive. Perhaps there are regional differences, I haven’t checked.
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Interesting. I have only used goodlabs once but I don’t think it gave me options as to where to perform the test themselves. It directed me to a different name altogether and it was called Bioreference labs. Next time I do lab work I’ll see if it allows me different options.
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Incase this helps… there is a dropdown here… and now I’m seeing bioreference for the first time. It turns out they are only available in ny/nj.
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Actually, I just realized that and yes LabCorp seems cheaper than Bioreference. Next time I’ll pick LabCorp. Thanks for the heads up, as i mistakenly thought there was only one choice-bioreference.
edit: no, quest is way cheaper than both, I hadn’t checked Quest yet LOL
Clearly only Bioreference is supported in NY/NJ. I’m pissed would have been way cheaper with quest, over $100 saving compared to bioreference for same tests.
“For NY and NJ, only the Bioreference lab is supported. Please enter a zip code outside of NY/NJ or select the Bioreference lab”
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@SilentWatcher I found your posting interesting would you mind elaborating.
What would you consider an ideal scenario of taking metformin, in a time frame of one week as an example. i.e. the dose, how often (morning or evening), in combination with what typical diet, and amount of exercise etc.?
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Good Labs is not available in my area. I use ultalabtests.com; they are significantly cheaper than LabCorp or Quest. They are very straightforward, and you can choose either LabCorp or Quest to have your labs done. Quest price for CMP: $44.10; Ulta Lab price: $22.95
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Not available in NY/NJ where I live. Could’ve done CT (not too far from where I live) but I’d called a while back and they told me I needed to show a CT ID. Kind of suck because they are pretty cheap. Stuck with Goodlabs bioreference which are about 30% cheaper than going with LabCorp or quest directly (in my area/state). still more expensive by about 30-40% than other options in other states.
Scientists in the US and Germany used data from a long-term US study of postmenopausal women. Records for a total of 438 people were selected – half of whom took metformin to treat diabetes, and half who took a different diabetes drug, sulfonylurea.
While there are some caveats and asterisks to the study, those in the metformin group were calculated to have a 30 percent lower risk of dying before the age of 90 than those in the sulfonylurea group.
“Metformin has been shown to target multiple pathways of aging and therefore has been postulated as a drug that may extend human longevity,” write the researchers in their published paper.
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Yes, metformin is much better than sulfonylurea. No one should take the latter when they can take Metformin instead. Do any doctors.still prescribe it?
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Metformin Turns Back the Epigenetic Clock in Non-Human Primates: A 10-Year Human Equivalent Study
Metformin, the derivative of biguanide synthesized in the 1920s and approved by the FDA in 1994 for type 2 diabetes, has demonstrated substantial geroprotective benefits in non-human male primates. In a recent study by Yang and colleagues, healthy cynomolgus monkeys aged 13-16 years (equivalent to 40-50 human years) received daily metformin for 3.3 years, effectively mirroring a decade of human administration.
Instead of isolating a single biomarker, researchers tracked the DNA methylome, transcriptome, proteome, and metabolome across 79 distinct tissues and organs. The results present a systemic deceleration of the aging process. By utilizing an Elastic Net regression model, the study calculated that metformin decreased systemic protein age by an average of 6.41 years. The drug successfully inhibited age-driven inflammation, cell death, and fibrosis, while reactivating suppressed pathways governing lipid metabolism, Wnt signaling, and DNA repair mechanisms.
Neurologically, the outcomes were robust. Metformin displayed significant neuroprotection in the frontal lobe and hippocampus, reducing amyloid-β and p-Tau accumulation, while enhancing synaptic connectivity and neuronal regeneration. Frontal lobe DNA methylation age regressed by 6.1 years, highlighting metformin’s potential in delaying the onset of cognitive decline and Alzheimer’s disease.
Source:
- Open Access Paper: Metformin: decelerates biomarkers of aging clocks
- Journal: Signal Transduction and Targeted Therapy, November 2024
- Institutions: Baker Heart and Diabetes Institute, The University of Melbourne, Monash University (Australia); The Chinese University of Hong Kong (China)
- Impact Evaluation: The impact score of this journal is 40.8, evaluated against a typical high-end range of 0-60+ for top general science, therefore this is an Elite impact journal.
Technical Biohacker Analysis
Study Design Specifications
- Type: In vivo.
- Subjects: Cynomolgus monkeys (non-human primates).
- Sex: Exclusively Male.
- Age Cohorts: Treatment group aged 13-16 years. Additional cohorts included middle-aged (10-12 years) and young (3-5 years) monkeys.
- Dosage: 20 mg/kg daily.
- Duration: 3.3 years (approx. 10 human equivalent years).
- N-number: Specific N-numbers per group and control size are omitted in the research highlight.
Lifespan Analysis & Data
- Lifespan Analysis: Not Applicable. This study evaluated in vivo epigenetic, proteomic, and transcriptomic clocks in non-human primates, rather than survival curves or maximum lifespan. Comparisons to short-lived murine control standards are currently impossible without hard mortality data.
- Lifespan Data: Hard survival extension in absolute time or percentage is not available. Surrogate biomarker data shows a decrease in protein age by 6.41 years and a rescue of frontal lobe DNA methylation age by 6.1 years.
Mechanistic Deep Dive
- Nrf2-Keap1 Antioxidant Axis: Metformin’s reduction of oxidative stress is mediated heavily through the nuclear factor erythroid-derived 2-like 2 (Nrf2). Under normal physiological conditions, Nrf2 is tethered and inactivated by Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm. Oxidative stress triggers a conformational change at Keap1 residues C273 and C288, destabilizing the complex. Freed Nrf2 translocates to the nucleus, forms a heterodimer with small musculoaponeurotic fibrosarcoma (sMAF) proteins, and binds the antioxidant response element (ARE) to transcribe cytoprotective genes such as HO-1, NQO-1, SOD3, GPX1, and GPX2.
- Epigenetic Maintenance: The study identified that metformin restores levels of H3K9me3, the loss of which is a recognized marker of aging and is heavily implicated in premature aging syndromes like Werner and Hutchinson-Gilford progeria.
- Cell Cycle Regulation: Metformin attenuated the age-related decline of p21-positive cells in the liver, lungs, kidneys, heart, skin, and stomach, which correlates with reduced fibrotic changes and lipid peroxidation. Critical Note: The authors state that p21 suppresses genes involved in cell cycle arrest. This contradicts canonical cell biology, where p21 acts as a cyclin-dependent kinase inhibitor that induces cell cycle arrest. This mechanistic claim requires severe scrutiny.
- Organ-Specific Triage: The brain exhibited the highest clock reversal. DNA methylation age regressed by 6.1 years in the frontal lobe, followed by the lung (5.11 years), kidney cortex (4.9 years), liver (3.95 years), and skin (2.65 years). Single-nucleus transcriptomic age in microglia and oligodendrocytes regressed by 6.86 and 6.79 years, respectively.
Novelty
This highlights the leap from short-lived, metabolic-fragile murine models to genetically proximate non-human primates over a clinically relevant, multi-year timeframe. It quantifies geroprotection through a highly comprehensive integration of epigenomics, transcriptomics, proteomics, and metabolomics into a unified clock algorithm.
Critical Limitations
- [Confidence: High] Sex Bias: The study exclusively utilized male monkeys. The authors openly acknowledge that females experience higher incidences of dementia and cognitive decline, meaning this data is fundamentally incomplete for half the human population.
- [Confidence: High] Missing Upstream Mechanisms: The exact kinase pathways upstream of Keap1 dissociation remain unverified. The paper’s own diagram lists PKC and AMPK signaling pathways with question marks, indicating speculative biological links.
- [Confidence: Medium] Biomarkers vs. Functional Lifespan: An Elastic Net regression model proving an epigenetic age reversal of 6.41 years does not empirically guarantee a 6.41-year extension in physiological lifespan or functional healthspan. Long-term survival tracking remains the required missing variable.
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How many people here use a health band like Hume to monitor all the drugs and supplements they are taking?