Interesting article by Saavedra, but perhaps too optimistic about ARBs than than the evidence suggests. Summarizer: “This is a useful compendium of the pleiotropic pharmacology of ARBs, and the core idea — that RAS dysregulation contributes to diverse pathology — is well-supported. But the leap from “ARBs do interesting things in cell cultures and rodents” to “ARBs should be used for Alzheimer’s, depression, and menopause” needs much more clinical trial evidence than currently exists. The review is better as a research roadmap than as clinical guidance.“
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Now you know that isn’t a fair statement - that olmesartan outperformed the other meds. At least based on what you quoted.
They weren’t compared to each other and the confidence intervals are overlapping - and not by just a little bit.
I do seem to remember there was one situation where olmesartan did outperform talmisartan but not in the data you quoted.
Look at table S4 “Adjusted Hazard Ratios for Dementia Risk Across Individual ARBs”. So this is within class of ARBs. Irbesartan was the reference (based on neutrality in previous studies), and olmesartan stood out for significance (p value >0.001). Within ARBs using Irb as reference (AHR 1.00) Olme was 0.55 Telmi 0.94 (NS). And the CI on Olme was 0.43-0.71, whereas Telmi was completely outside the Olme range 0.84-1.05.
For ACM see table S9 and the within class (ARBs) numbers - again Olme was the lowest 0.64 vs Telmi 0.91. And the CI were non overlapping with Olme 0.56-0.74 and Telmi 0.85-0.97.
Keeping in mind we are dealing with decent size cohorts, not a handful of subjects.
After all this time, 40 or 80 for longevity? 
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I don’t know that the thresholds are well understood for broader benefits. Taking 80 mg/day, the mean reduction in systolic blood pressure is approximately 12–13 mmHg and diastolic blood pressure is ~ 7–8 mmHg. For many, the limiting factor will be their baseline BP. A person with high normal BP can likely take a full 80 mg dose and still have adequate, perhaps optimal BP. That is my situation. A person with mid-normal or lower baseline BP will have to see if they can maintain adequate BP with 40 mg or 20 mg. Many normotensive people are reporting doing well and actually improving their BP profile taking either 20 or 40 mg/day. I do very well, with no dizziness or other symptoms with a mean BP of 104/62. Empirical. No hard formula and your minimums may vary.
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For anyone taking Telmisartan, preferably at 80 mg’s or above, look into cold exposure. I find they couple incredibly well, mood is vastly enhanced with their synergy. Gemini gave several rationales, perhaps this is relevant:
Shifting the Telmisartan BAT Engine into Gear
This is the most fascinating cellular synergy. Telmisartan upregulates UCP1 and alters fat-pad macrophages to “prime” your white fat tissue, turning it into metabolically active beige fat. However, without a physical stimulus, those newly created beige mitochondria are like a high-performance sports car sitting in neutral.
The Cold Shower Correction: Cold exposure is the physical key that turns that engine on. The cold activates the newly formed UCP1 channels to start aggressively burning those cleared fats to generate heat. Instead of your body feeling sluggish from telmisartan’s nutrient-clearing process, the cold exposure forces your body to cleanly consume that fuel for thermogenesis, completely optimizing your full-body energy expenditure.
Having just started taking cold showers, I am quite befuddled as the lack of attention to cold exposure for health- and lifespan promotion. We shower anyway, so why not optimise its effects on our physiology. Rhonda Patrick has a good overview of the literature.
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If you are going to do this for a while you should get a scan done and another after doing this for a few months.
Cold showers are not how you do CE (cold exposure). Back when the CRSociety website was active, we had a years long exploration of CE as a rival to CR (calorie restriction). CE can be an incredible longevity tool. There is a long list of interventions which increase BAT, but CE is the most reliable. If you want to do real CE, cold showers (or cold plunges) are not it (or only a tiny part for beginners), for real CE you need much longer exposure, on the order of hours. To do that in practical terms, you use a cold vest. There is a variety of designs, several available on Amazon, or make your own. It involves inserting ice packs into a specially constructed vest with the ice packs hitting key areas, such as trapezoids where BAT generation is most activated. You increase the time you wear the vest gradually, starting with a few minutes. Eventually you get it long enough to get substantial benefits.
Re: telmisartan and BAT, I am not familiar with this interaction, but I’m very familiar with CE, so I thought I’d chime in 
FWIW, I’ve mentioned CE as a longevity intervention in seversl threads here, but indeed it’s a topic almost never discussed on the site - strange, considering CE can rival CR for longevity. But of course, pharmaceuticals are more the focus here - it’s in the name 
!
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did you mean trapezius muscle/area? as I’m not familiar with a trapezoid area in human body, real question btw,
Sorry, yes, that’s what I meant, somehow my fingers went geometric😅.
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Thanks
I didn’t know about that. That is something I might try. For some reason, perhaps because I spent my youth in cold country and most of my adult life in the desert, I am very tolerant of heat and cold, but I’m not into cold showers.
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Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes
https://www.kidney-international.org/article/S0085-2538(16)30590-7/fulltext
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This is a very complex paper. I’m still digesting it. Thanks.
This really is a very nice paper looking at the kidney protection afforded by telmisartan vs enalapril so, you are looking at class effects ARBs vs ACEi (in diabetics). What’s very nice is that it is not a short term trial, but five years 
- and it’s randomly assigned, prospective, multicenter, double blind with 250 subjects. Telmisartan was the ARB and it was at a dose of 80mg (so, you are looking at max effects dose), while enalapril was at 20mg. Primary endpoint was GFR with several secondary endpoints. It’s also a very old trial and somehow it escaped my attention. Enjoy!
Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy
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My interpretation of the more recent findings on kidney health trajectories in aging is that there is no definite answer. The field displays the characteristics of a high flux focus.
Some may have missed that in the parent TRANSCEND renal-outcomes paper which specifically tested telmisartan versus placebo on the long-term eGFR trajectory we see a different trajectory. In adults with vascular disease without macroalbuminuria, over 4–5 years eGFR decreased more with telmisartan than placebo and the difference was not trivial. Moreover, doubling of serum creatinine was more frequent on telmisartan while albuminuria increased less with telmisartan. The overall composite renal outcome was neutral.
The population in which TM slowed decline was in the proteinuric diabetic nephropathy (RENAAL, IDNT, the ACE-inhibitor nephropathy trials), where the pathophysiology is hyperfiltration through a reduced, high-pressure nephron mass.
Even this looks to me like the tip of the iceberg and there are other dimensions to unpack and discuss when time permits.
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From the paper you cited:
“Twenty subjects in the telmisartan group and 30 in the enalapril group had adverse events necessitating discontinuation, despite the fact that all had received ACE-inhibitor therapy”
That was a fairly high percentage of dropouts.
Just a reminder to all who self-experiment with drugs, etc. Do only one at a time and try to keep other variables the same until you find out the effects of the new drug or supplement you are taking.
I recently had this experience with telmisartan when changing from 40 to 80 mg daily. I started experiencing muscle pain at night, mostly in my arms. It took me a little while to figure it out. But because I had only changed one variable in my daily routine, it didn’t take too long to figure out the problem. Who knew? I have been taking 40 mg of telmisartan daily for the better part of a decade with no adverse results. Apparently, changing to 80 mg a day pushed me over the edge.
Going back to 40 mg a day solved the problem.
I described my problem to Gemini Pro along with the meds and supplements that I take.
Gemini:
The most likely culprit is telmisartan. Temisartin belongs to a class of drugs called ARBs (angiotensin receptor blockers), which have side effects that closely match your experience:
- Muscle and Back Pain: Myalgia (muscle aches) and back pain are well-documented side effects of telmisartan.
- Dose Dependency: Because your prescription recently doubled from 40 mg to 80 mg, your body is processing a significantly higher amount of the active ingredient. Side effects often emerge or worsen when a dose is increased.
- Timing: Taking the medication in the evening means it reaches its peak concentration in your bloodstream while you are sleeping. This perfectly aligns with the pain waking you up a few hours after you go to bed and resolving shortly after you get up and the drug’s peak concentration begins to ebb.
Because you do regular resistance training, you know exactly what standard post-workout muscle fatigue feels like. Your instinct that this new, position-independent ache is something entirely different is spot on.
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This study has much going for it and a few important limitations. To employ the findings one would want to qualify for membership.
Strengths: Prospective, multicenter, double-blind, five-year study, 250 subjects with type 2 diabetes and early nephropathy. Randomization to telmisartan 80 mg or enalapril 20 mg, with the primary end point being change in GFR determined by plasma clearance of iohexol.
Weaknesses: No control arm. Both arms got RAS blockade. Telmisartan changed GFR by −17.9 mL/min/1.73 m^2 over five years versus −14.9 for enalapril, meeting the criteria for noninferiority. So “renoprotection” means “about as good as enalapril,” not “better than not taking it.” There is no counterfactual. The external comparison is that untreated diabetic patients with proteinuria decline at 10–12 mL/min/1.73 m^2 per year which is a historical benchmark, not a randomized one.
This study enrolled T2D with albuminuria and hypertension, mean age 60, entry GFR >69 – a hyperfiltering diabetic nephropathy cohort in late middle age which is a population where the intraglomerular-pressure story has held. The study has little to say about a large group of which I am an example – 70–80s, non-diabetic or non- or barely dysglycemic, metabolically healthy, largely non-proteinuric, age-appropriate mean eGFR 55–75.
I’ve posted this study in another thread a while ago, but seems relevant in the current discussion. CAUTION: Indian study!!!
Assessing Renoprotective Effects of Empagliflozin and Telmisartan Combination Therapy in Non-albuminuric Diabetic Nephropathy: A Retrospective Cohort Study
Bottom line combo therapy (tel + empa) was more effective compared to monotherapy in kidney protection.
And for good measure another study of tangential interest, but CAVEATS: (1) in rats (2) Chinese.
Note: henagliflozin is an SGLT2i cleared for use in China, but nowhere else.
Pharmacokinetic interactions between three SGLT2 inhibitors and telmisartan: A focus on empagliflozin, ertugliflozin, and henagliflozin
Bottom line telmi + empa don’t have significant DDI compared to telmi + ertu or telmi + hena.
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The obvious limitation of drug studies is that these drugs are naturally tested for primary indication, i.e. people who have the various morbidities the drug addresses. Meanwhile biohackers are trying to use the drugs for different purposes altogether, whether prevention, preservation or enhancement in the absence of those morbidities. As expected, there is going to be a huge margin of uncertainty about the effects of these drugs in healthy people. Here’s another study, again in frank diabetics with seriously compromised renal function (lowish GFR). Furthermore, renoprotective drugs work on different aspects of kidney health. Here’s one that focuses on albuminuria.
Optimization of Albuminuria-Lowering Treatment in Diabetes by Crossover Rotation to Four Different Drug Classes: A Randomized Crossover Trial
Several takeaways: different classes of drugs can work for different people - what might be effective in one, might not be in another. I was surprised to see the relative success of telmisartan purely in the number of respondents - I’d have expected the SGLT2i to be more broadly effective. I also thought it notable that RAS inhibitors have such a large percentage of non-responders. The takeaway is that for kindey protection, you should probably stack drug classes, because you might not be able to look at a study where, say, telmisartan is renoprotective and expect it to have the same effect for you - you might be a non-responder. And if you do use combo drugs, it might be advisable to carefully look at DDI (for example, perhaps if using telmisartan it is better to pair it with empagliflozin compared to, say, ertugliflozin etc. - per the study I posted in the previous post). Carefully measure your kidney health indicators, and then test the effect of every drug and drug combination to see how the numbers shift, and that way you may be able to arrive at the best drug stack for your physiology.
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Continuing with the theme of drug combinations for renal protection we can add statins. This here is in rats - CAVEAT: Chinese paper!!! These are spontaneously hypertensive rats - so renal damage is due to HT and not diabetes - important to show broad applicability, as we’ll see in the paper after this one. The arms were: telmisartan treated, pitavastatin treated, and telmisartan + pitavastatin treated.
Adjunctive therapy with statins reduces residual albuminuria/proteinuria and provides further renoprotection by downregulating the angiotensin II-AT1 pathway in hypertensive nephropathy
“The combination treatment with telmisartan and pitavastatin displayed a more effective decrease in albuminuria and proteinuria, even to the normal level. Enhanced nephroprotection was also observed in this combination group, which was independent of the cholesterol-lowering effects. Further mechanistic studies revealed that the combination therapy greatly attenuated the expression of intrarenal Ang II and AT1, thereby decreasing the activation of TGF-β-Smad and NF-κB and inhibiting fibrosis and inflammation.”
“Adjunctive therapy with pitavastatin dramatically reduced residual albuminuria/proteinuria and enhanced nephroprotection, likely by downregulating the expression of intrarenal Ang II and AT1. It could be concluded that statins might be a promising adjunctive therapeutic agent to conventional ARB treatment in hypertensive renal damage.”
The next paper is a little crazy, as it puts together both ACEi and ARB before adding a statin. Here in turn, we are dealing with rats with induced diabetes renal damage, so different from the strictly HT nephropathy in the previous paper. And yet, the addition of a statin was protective. This tells us that statins are broadly renoprotective in combination therapy regardless of the way nephropathy has been achieved.
Adding a statin to a combination of ACE inhibitor and ARB normalizes proteinuria in experimental diabetes, which translates into full renoprotection
https://journals.physiology.org/doi/full/10.1152/ajprenal.00045.2010
FWIW, my drug stack has all three drugs in it: telmisartan 80mg/day, empagliflozin 25mg/day, pitavastatin 4mg/day. My kidney markers have been excellent, but I cannot stress enough that everyone needs to develop their own stack based on rigorous testing extended in time. The time element is super important because there are many counterintuitive short term effects vs long term effects (as in an SGLT2i and telmisartan sometimes initially dropping GFR numbers before recovering within a year or so).
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