Are the articles in rats relevant? Unless the doses tested were equivalent to 40 and 80 mg in humans?
The first one is interesting. I remember others for insulin resistance but I thought they tested 20 vs 40 mg.
In any case the paper I posted used 40 mg so… All good?
Rats/mice here are as relevant (or not) as animal models in other studies, including NDDs. Hypothesis generation, mechanism illustration etc. I cited studies in animal models because many of these can’t in practice be done in humans, or weren’t done.
Re: 40 mg vs 80 mg, well, it’s somewhat relevant because we have different effects even in BP control. The purely off target pleiotropic effects would start at something higher, like 160mg, because there are no longer significant BP effects above 80mg, where for primary indication there’s no reason to go higher. That’s where the other effects might be seen more prominently. Unfortunately there are very few studies using 160mg as that’s no longer a clinical dose for primary indication (BP) so we have to turn to animal models to look for signals (rats and mice in the above studies). But like I said, I would think it’s relevant whether it’s 40mg or 80mg, because there are different effects even on BP.
Telmisartan is one of the drugs that I’ve been doing a deep dive on (SGLT2i empagliflozin, statins pitavastatin, LLT bempedoic acid, ezetimibe, rapamycin, everolimus, pioglitazone), because I am interested in neuroprotection, NDDs (especially, but not limited to PD), and there most often the effect is obviously not the primary indication. So I have to look for off target effects and pathways, which often are strongly dose dependent. And unfortunately there are few direct studies, so you look to signals in animal models as a guide.
I don’t get your point: are you looking at taking 160 mg? Or even more? Just take 80 mg and that’s it?
I’m taking 80mg/day at present. I am considering 160mg/day pending further research. Should I decide to take 160mg, the earliest that would occur is June 2026, after several months of low dose (7.5mg/day) of pioglitazone. There are many reasons to consider the simultaneous use of pioglitazone and telmisartan, which I have explored in the pioglitazone thread, and dosage is important in that context. There are some additional considerations in that I also take 25mg/day of empagliflozin. When looking at polypharmacy, dosages of the individual drugs become even more important (such as the stacking of BP effects among others).
I wish I could take Telmisartan 20 mg, but I can’t as it lowers my BP too much. However, I did start taking Tadalifil, and that does not cause my blood pressure to go too low. I feel good overall without having the effects of too low a BP. The benefits of Tadalifil for my prostate is also a bonus.
Preprint: Telmisartan reduces systemic inflammation and alters the renin-angiotensin system in mild COVID-19 2025
@adssx I dropped that study into Gemini and (while I haven’t been following Telmisartan much at all due to my good blood pressure numbers), this caught my eye (see below). What do you think of the broader research around Telmisartan as a anti-inflammaging and fibrosis medication?
From the summary of the paper you posted today:
Researchers from the University of Southern California and the University of Hawaii have provided clinical and molecular evidence that the antihypertensive drug Telmisartan acts as a potent metabolic switch during acute viral stress. While the study focused on mild COVID-19, the implications extend far beyond viral defense into the core mechanisms of inflammaging and vascular fibrosis.
The central finding is that Telmisartan does more than lower blood pressure; it fundamentally alters the “software” of the Renin-Angiotensin System (RAS). In untreated patients, the RAS system is often hijacked to favor Angiotensin II, a peptide that drives vasoconstriction, inflammation, and aging. Telmisartan treatment (40 mg/day) successfully blocked this pathway and upregulated the “pro-resolving” arm of the system: ACE2 and MasR. This shift increased levels of Angiotensin(1-7), a peptide known for tissue repair and anti-inflammatory effects.
Then I queried about the broader scientific and clinical research around telmisartan and any possible benefits for inflammaging and fibrosis, and got the following result.
I know you’ve looked more closely at this, but does all this sound accurate to you?
While the provided study highlights acute inflammatory modulation in viral infection, broader research paints a more compelling picture of Telmisartan as a systemic geroprotector. It is distinct among the “sartan” class (Angiotensin Receptor Blockers, or ARBs) because it possesses a dual mechanism: it is both an AT1 receptor blocker and a partial PPAR-gamma agonist. This unique pharmacological profile allows it to target two central pillars of aging: inflammaging (chronic sterile inflammation) and vascular fibrosis (tissue stiffening).
1. Inflammaging: The “SASP” Silencer
Research indicates that Telmisartan acts as a senomorphic agent—a compound that does not necessarily kill senescent cells but suppresses their toxic secretions (the Senescence-Associated Secretory Phenotype, or SASP).
- The AMPK/mTOR Autophagy Switch: Unlike other ARBs (e.g., valsartan, candesartan), Telmisartan has been shown to uniquely activate AMPK and inhibit mTOR in microglial cells. This is the “holy grail” mechanism of fasting and rapamycin. By flipping this switch, it induces autophagy, allowing immune cells to clear cellular debris rather than spewing inflammatory cytokines like IL-6 and TNF-alpha.
- Neuro-Inflammaging: Because Telmisartan is highly lipophilic (it dissolves in fats), it crosses the blood-brain barrier more effectively than older ARBs like Losartan. Once in the brain, its PPAR-gamma activity reduces neuroinflammation, protecting against the cognitive decline associated with “inflamed” aging.
- Systemic Cytokine Blockade: Beyond the viral context, Telmisartan inhibits the NF-kB pathway, a master regulator of inflammation. In models of colitis and systemic endotoxin stress (LPS), it significantly blunts the release of pro-inflammatory cytokines, acting as a metabolic shield against chronic immune overactivation.
2. Vascular Fibrosis: The “De-Stiffening” Agent
Aging is characterized by the stiffening of arteries, driven by the replacement of elastic fibers with rigid collagen—a process controlled by TGF-beta. Telmisartan appears to directly intervene in this calcification of the vascular tree.
- Blocking the Fibrosis Master Switch (TGF-beta1/Smad3): Research confirms that Telmisartan downregulates the TGF-beta1/Smad3 signaling pathway. In hypertensive models, this prevents the differentiation of vascular fibroblasts into myofibroblasts (the scar-forming cells), effectively halting the structural remodeling that leads to “old,” stiff vessels.
- Reversing Arterial Stiffness (Pulse Wave Velocity): Clinical data backs the mechanism. In a study of hypertensive type 2 diabetics, Telmisartan significantly reduced **Carotid-Femoral Pulse Wave Velocity (cf-PWV)**by 0.95 m/s compared to placebo. A reduction in PWV is a functional biomarker of “vascular rejuvenation,” indicating that the arteries have become more compliant (elastic).
- MMP Regulation: As hinted at in the provided PDF, Telmisartan modulates Matrix Metalloproteinases (MMPs). By balancing MMP activity (specifically inhibiting pathological MMP-2 and MMP-9 in some contexts while modulating MMP-1), it preserves the structural integrity of the extracellular matrix, preventing the “saggy” and “stiff” phenotype of aged tissues.
3. The PPAR-gamma “Goldilocks” Effect
The defining feature of Telmisartan in longevity research is its Partial PPAR-gamma Agonism.
- Metabolic Synergy: Full PPAR-gamma agonists (like the diabetes drug Rosiglitazone) are powerful metabolic regulators but come with dangerous side effects like weight gain, fluid retention, and heart failure. Telmisartan activates the receptor to only ~25–30% of its maximum potential.
- The Sweet Spot: This partial activation is sufficient to improve insulin sensitivity, boost mitochondrial biogenesis, and lower inflammation, but it avoids the severe side effects associated with full agonism. It acts as a “metabolic modulator,” improving the way the body handles glucose and lipids without the toxic overhead.
Full Gemini Analysis: https://gemini.google.com/share/769856293e99
I am on 160 mg Of Telemisartan for nearly a year now. I am taking it for the PPAR agonism. Monitored potassium - initially it went upto 5, now it has settled at 4.75. Pleased with it. I am experimenting to increase my insulin sensitivity but no clear cut outcome. I am also on Pioglitazone 7.5mg and the polypharmacy muddles the picture and now the peptides are muddling it more. There will be light at the end of the tunnel!
I have read that telmisartan is used to prevent kidney decline in those with CKD (chronic kidney disease) even with a normal BP. Based on graphs I’ve seen of kidney function over time, specifically Cystatin C with age, basically everyone gets CKD eventually without any intervention.
Activation of the renin-angiotensin-aldosterone system (RAAS), especially angiotensin-2 is involved in CKD pathogenesis and its cardiovascular complications.[10] Drugs interfering with the renin-angiotensin system, i.e. angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARBs) are of choice as they have a blood pressure-independent antiproteinuric effect. During therapy with ACE inhibitors, angiotensin II escape prevents complete RAAS inhibition, due to alternative non-ACE pathways. However, ARBs overcome this limitation by selective blockade of the AT1 receptor and therefore angiotensin II escape observed with an ACEI do not occur with an ARB.[11,12] They are used to maximize RAAS inhibition and more effectively reduce proteinuria and decrease in GFR in diabetic and nondiabetic renal disease.[10] ARBs reduce protein excretion by approximately 35% to 40%, which is greater than other antihypertensive agents.[13] As CKD continues to rise, measures to prevent disease progression is an important goal. Among RAAS inhibitors, ARBs are preferred because of advantage discussed earlier and also because of the fact that ACE inhibitors are known to cause dry cough in a higher proportion of the Asian population. Literature search did not reveal specific study with telmisartan carried out in real-life setting in Indian patients. The aim of the present study was to examine the effects of telmisartan in patients with CKD.
Telmisartan is used to prevent kidney decline in CKD? But it can also cause renal injury? Does anyone know if a drug like this could be preventative to try and slow down kidney aging / EGFR decrease over time independent of BP effects? I know Peter Attia had trouble some while ago finding a nephrologist working in prevention.
Thanks. No sources provided by Gemini so hard to comment. Telmisartan is indeed a great drug, probably the best antihypertensive. I’m taking 80 mg.
That’s interesting. I am currently on 80mg/day of telmisartan and interested in 160mg. I was going to pair it with pioglitazone 7.5mg/day, but all my plans went out the window because of unexpected surgery coming up (ACDF) involving fusion of a couple vertebra in my neck with titanium plate and screws. The bone fusion is critical and can take up to 18 months. Since pioglitazone is a negative for bone health (suppresses osteoblasts, can enhance osteoclasts), I don’t want to risk poor bone fusion in my cervical spine. This means at least an 18 month delay of the pioglitazone for me.
Can you speak to your experiences/results of the 160mg telmisartan dose? Thx.
I too had a cervical fusion, except no Ti plates but bone graft from iliac crest. I had broken C5 and C6 at the age of 18! Anyways many moons ago!
I am afraid other than my potassium levels I cannot speak to anything. My BP did not change between 80 and 160 other than day to day fluctuations, nothing ascribable. Tell me what I should be looking for and I will respond. My Hba1c is around 7.2, had been as high as 12, but this decrease is due to Semaglutide and Tirzapetide. I am continuing with 160 because I did not experience anything negative and I can tolerate the added cost.
Among other good things, combining Telmisartan and an SGLT2 inhibitor creates a “bookend” geroprotective for aging kidneys. Telmisartan acts primarily at the efferent arteriole (glomerular exit), while SGLT2 inhibitors act at the proximal tubule and afferent arteriole (glomerular entrance). The two create synergistic hemodynamic and metabolic protection. It is a combination worth considering by older adults, including those whose BP is at least toward the middle of the normal range. My long term mean systolic BP was 118 before initiating telmisartan but the standard deviation was high. Adding 80 mg. Telmisartan lowered the mean to ~108 and significantly lowered the SD below the equivalence of the lower mean (another discussion but adding 250 mg. aged black garlic dropped my mean systolic further to ~104 – I’m leaving it there). Currently, I’m taking 5 mg. Canagliflozin but may increase that to 10 mg. at some point after re-assessing kidney function metrics.
After controlling for major modifiable lifestyle factors such as diet and physical activity, ARB use was linked to a significantly reduced risk of dementia compared with ACEI use (hazard ratio [HR] = 0.72; 95% confidence interval [CI]: 0.65-0.80, p < 0.001). In exploratory agent-level analyses, compared with lisinopril, olmesartan (HR = 0.32; 95% CI: 0.16-0.62), candesartan (HR = 0.41; 95% CI: 0.24-0.69), telmisartan (HR = 0.42; 95% CI: 0.25-0.71), irbesartan (HR = 0.45; 95% CI: 0.27-0.75), and perindopril (HR = 0.52; 95% CI: 0.31-0.87) were associated with a significantly lower risk of dementia, while captopril showed a significantly increased risk (HR = 4.9; 95% CI: 1.04-23.4).
Thanks for that study - no paywall! this is an Australian 250k cohort followed for 11 years. Also in there is a statistically significant reduction in all cause mortality with ARB vs ACEi. And what seems to be a decent look at compliance - an issue since ACEi have more annoying side effects than ARB so there could be a significant compliance effect on outcome.
Does make you wonder why everyone hasn’t switched entirely to ARBs?
The Captopril number is based on only 36 events and the confidence interval is so wide. They mention that in the discussion.
Also, all the various ARB confidence intervals overlap quite a lot. So their overall interpretation is class effect rather than any particular drug which seems reasonable to me. But then so much for talmisartan being unique here although I know there are other studies.
The olmesartan signal is pretty interesting. Not even for the dementia effect, but the much bigger and in my eyes more significant effect of ACM. From the paper:
“All-cause mortality risk
Results indicated a significant reduction in the risk of death for ARB users compared to ACEI users (HR = 0.77; 95% CI: 0.73–0.82, p < 0.001). In exploratory agent-level analyses, olmesartan showed the greatest risk reduction (HR = 0.64; 95% CI: 0.56–0.74), followed by telmisartan (HR = 0.91; 95% CI: 0.85–0.97) and candesartan (HR = 0.92; 95% CI: 0.86–0.98) compared with irbesartan (Table S9).
ARBs showed varied mortality risk compared to lisinopril. Olmesartan was associated with the greatest reduction in mortality risk (HR = 0.34; 95% CI, 0.24–0.48) (Table S9). Perindopril was linked to the lowest risk of death among ACEIs (HR = 0.70; 95% CI: 0.50–0.86) compared with lisinopril (Table S9). After excluding patients whose hypertension diagnosis was based solely on AHM records, ARBs were significantly associated with the reduction of all-cause mortality compared with users of ACEIs (HR = 0.80; 95% CI: 0.75–0.85) (Table S9).”
For dementia the HR difference between olmesartan and telmisartan is a more modest 0.32 vs 0.42, but look at that giant chasm in ACM - 0.64 vs 0.91! That is huge! And to me the most important aspect of this is not even the size of the difference, but the fact that in the case of the other ARBs like telmisartan the ACM lowering is barely there at 0.91, whereas the impact of olmesartan is a hefty, substantial, meaningful 0.64. You could almost say that olmesartan lowers ACM and telmisartan does not(of course we are talking comparatively here!). Again, all this is comparatively, important not to forget.
What good is it to natter on about ppar-gamma, glucose, lipid control and pleiotropic effects of telmisartan if it doesn’t lower ACM? Well, olmesartan may have no impact on ppar-gamma, but so what, it impacts what ultimately really matters, all cause mortality.
Of course, there’s a giant asterisk to all of this. The ACM effect here is observed in hypertensive subjects. Additionally, we don’t know if this is down to the BP lowering effect - and let us note, olmesartan is a more powerful BP lowering agent among ARBs than any other including telmisartan. And this - BP lowering size effect - was not controlled for in this study (Strengths and Limitations section):
“Finally, the lack of blood pressure (BP) measurements and longitudinal data prevented adjustment for differences in baseline BP, achieved targets, or treatment intensity. As BP management is central to vascular and brain ageing, class- or agent-specific dementia protection reported in this study should be interpreted cautiously without such data.”
Nonetheless olmesartan is an interesting drug, and deserves more attention from biohackers who mostly hyperfocus on telmisartan - ACM is what matters. I have posted about olmesartan before on this site, it has a different pleiotropic profile than telmisartan, and slightly more side effects (though that’s not saying much, seeing as telmisartan has virtually none!).
Obviously nobody should make decisions about picking a drug based on one observation study, but the study can still identify a drug worth further exploration, in this case olmesartan. YMMV.
Angiotensin II–Stimulating Antihypertensive Medications and Dementia-Related Neuropathology
https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2844919
“In this cohort study with 756 decedents, cumulative angiotensin II–stimulating exposure was associated with lower risk for some types of neuropathology relative to angiotensin II–inhibiting exposure. Long-term angiotensin II–stimulating exposure (≥15 years) was associated with a 24% lower risk for arteriolosclerosis.”
“In this community-based autopsy cohort study, angiotensin II–stimulating antihypertensive medications were associated with lower risk of neuropathological burden, supporting findings from epidemiologic dementia studies. Additional mechanistic research examining the effects of individual antihypertensive classes on Alzheimer disease–related biomarkers is warranted.”
Another win for ARBs.
For comparison some mortality and morbidity data for other HT med classes.
Mortality and Morbidity Among Individuals With Hypertension Receiving a Diuretic, ACE Inhibitor, or Calcium Channel Blocker
“A total of 32 804 participants (mean [SD] age, 66.9 [7.7] years; 17 411 men [53.1%]; and 11 772 Black participants [35.9%]) were followed up for all-cause mortality and a subgroup of 22 754 participants (mean [SD] age, 68.7 [7.2] years; 12 772 women [56.1%]; and 8199 Black participants [36.0%]) were followed up for fatal or nonfatal CVD through 2017 (mean [SD] follow-up, 13.7 [6.7] years; maximum follow-up, 23.9 years). Cardiovascular disease mortality rates per 100 persons were 23.7, 21.6, and 23.8 in the diuretic, CCB, and ACE inhibitor groups, respectively, at 23 years after randomization (adjusted hazard ratio [AHR], 0.97 [95% CI, 0.89-1.05] for CCB vs diuretic; AHR, 1.06 [95% CI, 0.97-1.15] for ACE inhibitor vs diuretic). The long-term risks of most secondary outcomes were similar among the 3 groups. Compared with the diuretic group, the ACE inhibitor group had a 19% increased risk of stroke mortality (AHR, 1.19 [95% CI, 1.03-1.37]) and an 11% increased risk of combined fatal and nonfatal hospitalized stroke (AHR, 1.11 [95% CI, 1.03-1.20]).”
I don’t know how to link, but table 3 is especially interesting, with ACM a big nothing in difference between these classes, which makes the ARB result in the other study quite interesting.
Say more please… My BP was always between 105-110/65-75 until last year or so now it is usually 115-125/75-80 still good but I’d like to start a BP lowering drug. Did we establish which one of these drugs is best in terms of overall benefits (not just blood pressure lowering effects) with least side effects. I was thinking low doses of either Telmisartan, Captopril, or Nebivolol. Any insight is greatly appreciated.
I’d prefer an ARB like telmisartan if I only needed one med to bring down BP by a relatively small amount. Not medical advice, just what I’d do personally.