If you want to learn from the experts on GLP’s and 12.5mg every other week is very high and many of us have started to transition to Retatrutide which is the next level of GLP’s than come over the the group at Jaycampbell.com . You can also see youtube videos of his partner Hunter Williams on youtube on GLP’s .
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No thanks, not interested in taking underground experimental drugs.
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Do you wear a sleep tracker and have you noticed sleep disturbances with tirzepitide?
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Hmm as someone with a couple of years experience prescribing a fair bit of these, I’d not assess 12.5 mg of Tirzepatide every other week high dose (given that 15 mg/week is the maximum).
I have 2 comments/queries:
#1 Taking Tirzepatide which has a 6 day half life every other week will not be near as effective as doing weekly dosing. My suggestion is 5 mg/week would be as effective as 12.5 mg every other week.
#2 Is the reason for this dosing use of a fixed pen (Mounjaro) and cost? If so, my suggestion is to get your prescriber to issue 15 mg pens, split that into 3 x 5 mg doses and do that weekly. You’ll likely have the same efficacy and a smoother serum level, and you’ve just saved 50% off your costs as 1 pen now will give 3 weeks of meds rather than 2.
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Who are the “many of us”?
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Haha, nice spamming. That website is a clown show.
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It’s not spamming and i’m sorry if you don’t see the value.
Yikes. So much disinformation on that site. Anyone purporting to claim to be in possession of Retatrutide are being disingenuous at best. Retatrutide is in clinical with Eli Lilly and has been for over a year. If your ‘source’ is claiming to have Retatrutide it is a compounded adjacent peptide that’s been wholly untested and is not the same Retatrutide being investigated currently.
I’m all for peptides and bioregulators but you can see for yourself, using the wayback machine that your buddies spam site was setup for sale of the peptide within a few days of the Retatrutide information being shared by Eli Lilly.
What are you actually injecting?
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What do you mean by “compounded adjacent peptide”?
I mean that in the sense that Retatrutide is a research chemical. However, the Retatrutide being run in clinical trials is almost CERTAINLY different than the one being pimped by the shady poster above. Eli Lilly owns the specific formulation and clinical application being trialed.
A compounding pharmacy may have a similar compound they’re actively marketing as Retatrutide. It’s not.
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A molecule is a molecule, but trusting the source in the “Wild West” of peptide research can definitely be a gamble.
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I would suspect many compounding pharmacies are making legitimate copies of GLP1 drugs, but if they are making Retatrutide, it would be illegal.
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Congratulations on a great result.
What you have achieved requires a huge amount of drive in addition to the medications listed.
Just one point to consider: I feel that the 40mg testosterone cypionate every second day might be considered to be a regular dose of TRT, but at about 140mg per week it can come with problems and at a lighter dose you will probably get very similar results but remove the risk of these SEs.
I would do blood tests for estrodiol, FSH, LH and also a full blood count to show your MCV (haematocrit).
If the FSH and LH are down to levels of 0.5 or less then it suggests you may be overdoing the testosterone and will get equivalent results at a lower dose.
If the estradiol is raised (>80 pmol/L) then you are converting too much testosterone into Estrogen which will cause weight gain amongst other issues.
If your MCV is greater than 0.49 then the testosterone is stimulating your bone marrow to thicken your blood which can worsen your clotting risk.
In our clinic we have moved away from the regular doses of TRT and have developed a protocol of what we call ‘micro-dosed testosterone replacement’ and found it to be both safe and beneficial.
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Yes, but the work around is occurring at all of the peptide companies with “not for human use” - yet, groups like peptidesciences have Retatrutide. They seemed to have pulled their Tirzepatide - not sure why and have Semaglutide. I have easy accessibility to quality PharmD produced Semaglutide and Tirzepatide from groups like Empower or Olympia.
https://www.peptidesciences.com/retatrutide-6mg
Interestingly groups like Peptide Sciences must be making huge profits as it seems like 60 mg of Tirzepatide probably costs less than $20 for pharma to produce - yet my compounders will give me 34 mg for $300 or 68 mg for $575. It’s still way cheaper than buying from the online “not for human use” outfits.
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Empower is a 503B also and has a lot more stuff than Olympia.
Their 17 mg/mL Tirzepatide 2 mL delivered cold with needles ends up being ~$325 … I use Empower a lot more - I find Olympia has a good deal on a 15 mg vial of Semaglutide but is more expensive on Tirzepatide. Yes on the BUD I don’t get that excited … and just make sure good cleaning of vial and sterile technique on drawing up - but yes - 30 days post first puncture is the rule.
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+1 for naproxen, if I had to choose an nsaid
Summary of the Matt Kaeberlein Video above:
I. Executive Summary
A large-scale retrospective pharmaco-epidemiological analysis evaluated the association between 406 commonly prescribed medications and all-cause mortality across 501,169 participants in the UK Biobank followed over 40 years (Morin et al., 2024). After adjusting for key survival confounders (age, sex, smoking status, prior cancer diagnosis, and diabetes) and enforcing a false discovery rate threshold (FDR < 0.05), 169 compounds significantly altered all-cause mortality. Of these, 155 medications were associated with increased mortality hazard ratios, reflecting confounding by indication, underlying disease severity, and polypharmacy toxicity. Conversely, 14 medications demonstrated statistically significant associations with reduced all-cause mortality, identifying candidate geroprotective compounds.
The 14 protective compounds clustered into specific pharmacological classes: phosphodiesterase-5 (PDE5) inhibitors, exogenous estrogens and hormone replacement therapy (HRT) formulations, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin receptor agonists, antimicrobial agents, and specific vaccines. PDE5 inhibitors demonstrated class-wide survival advantages in men (sildenafil HR 0.85; pooled class HR 0.86, p = 1e-5), mechanistically supported by systemic vasodilation, cyclic GMP (cGMP)–protein kinase G (PKG) pathway activation, and endothelial restoration. Exogenous estrogens dominated the protective signals in women across oral, transdermal, and localized vaginal delivery routes, yielding a pooled class HR of 0.76 (p = 5e-6), driven by cardiovascular risk reduction, bone density maintenance, and neuroendocrine preservation. Pooled sodium-glucose cotransporter 2 (SGLT2) inhibitors yielded an HR of 0.64 (p = 0.01), corroborating male lifespan extension data from the National Institute on Aging Interventions Testing Program (ITP).
Observational pharmaco-epidemiology contains inherent structural limitations. The non-linear dose response observed with atorvastatin (survival advantage restricted to low doses <= 20 mg/day) and the contradictory elevated mortality observed with ACE inhibitors (HR 1.10) demonstrate how observational cohorts can diverge from randomized controlled trials due to unmeasured confounding and disease severity. Canonical candidate geroprotectors like metformin demonstrated no mortality benefit (HR 1.00), while rapamycin and testosterone lacked sufficient statistical power for inclusion. These findings provide hypothesis-generating targets that require validation in randomized clinical trials.
II. Insight Bullets
- Cohort Scale and Electronic Health Architecture: The study analyzed 501,169 participants (ages 37–73) from the UK Biobank across 56,213,339 prescription events, highlighting the analytical power of nationalized electronic health registries compared to fragmented health data architectures (Morin et al., 2024).
- Prescription Filtering Thresholds: Evaluation was restricted to the top 406 prescribed drugs that met strict criteria: a minimum sample size of 500 patients and a minimum prescription duration of 3 continuous months.
- Control Cohort Matching Protocol: Drug-treated cohorts were matched against untreated controls using five dominant survival variables: chronological age at recruitment, biological sex, current smoking status, history of malignancy, and diagnosed diabetes.
- Correction for Multiplicity (FDR Control): Stringent False Discovery Rate (FDR < 0.05) corrections were applied across all 406 drugs to eliminate type I false-positive discoveries, which would otherwise generate approximately 20 false positives at standard p < 0.05 thresholds.
- Mortality Skew in Prescription Cohorts: Of the 169 statistically significant drugs, 155 (91.7%) were associated with elevated mortality, establishing that prescription drug usage in observational datasets generally serves as a proxy for baseline morbidity.
- Confounding by Indication and Polypharmacy: Elevated mortality across the 155 compounds is primarily driven by the lethal risks of the underlying diseases being treated and the compounding toxicity of polypharmacy in older populations.
- The Geroscience Premise: The 14 protective medications provide epidemiological evidence that specific approved molecules may modulate fundamental biological mechanisms of aging across multiple organ systems rather than solely addressing isolated symptoms.
- Atorvastatin Non-Linear Dose Response (#14, HR 0.91): Atorvastatin was associated with a 9% reduction in all-cause mortality, with the survival benefit concentrated at low-to-moderate doses (<= 20 mg/day), while higher doses exhibited loss of survival advantage or elevated hazard ratios.
- Diminishing Statin Dose-Efficacy Kinetics: The observed low-dose statin advantage aligns with clinical pharmacology showing that approximately two-thirds of maximal LDL reduction occurs at one-quarter of maximum dosage (~20 mg), after which incremental lipid lowering diminishes while adverse effect risks rise (CTT Collaboration, 2012).
- Murine ITP Statin Disconnect: Simvastatin failed to extend lifespan in the NIA Interventions Testing Program in mice, likely reflecting species-specific causes of death (mice predominantly die of lymphoma/sarcoma rather than atherosclerotic vascular occlusions) or suboptimal dosing protocols.
- Naproxen Divergence from Aspirin (#13, HR 0.90): Naproxen showed a 10% mortality reduction, whereas ibuprofen showed no significant effect (HR 0.99) and prescription aspirin showed increased mortality (HR 1.17), the latter driven by high-risk vascular baseline indications.
- NSAID Chronic Toxicity Trade-Offs: Despite naproxen’s statistical association, chronic systemic NSAID use carries well-documented risks of gastrointestinal ulceration, nephrotoxicity, and adverse cardiovascular events, accounting for over 15,000 deaths annually in the US (CNT Collaboration, 2013).
- Otomize Ear Spray Indication Bias (#12, HR 0.84): The apparent survival advantage of this topical dexamethasone/neomycin/acetic acid formulation likely reflects demographic selection bias (younger, higher socioeconomic status individuals presenting with uncomplicated otitis externa) rather than systemic geroprotection.
- Sildenafil Single-Agent Efficacy (#11, HR 0.85): Sildenafil demonstrated a statistically significant 15% reduction in all-cause mortality in men, reinforcing growing evidence that PDE5 inhibition exerts systemic vascular and metabolic protection.
- PDE5 Inhibitor Class-Wide Concordance: Parallel survival trends were observed across the entire PDE5 inhibitor class, including tadalafil (HR 0.86), vardenafil (HR 0.89), and branded Cialis (HR 0.77), culminating in a pooled class HR of 0.86 (p = 1e-5).
- PDE5 Mechanistic Targets: PDE5 inhibitors prolong nitric oxide-mediated cGMP signaling, activate protein kinase G (PKG), restore endothelial flow-mediated dilation, suppress systemic inflammation, and reduce myocardial hypertrophy (Andersson et al., 2017).
- Sumatriptan and Serotonergic Signaling (#10, HR 0.76): Sumatriptan (a 5-HT1D/1B receptor agonist) showed a 24% mortality reduction; while human aging mechanisms remain uncharacterized, serotonin receptor modulation extends lifespan in C. elegans and Drosophila models.
- Estradiol Systemic Geroprotection (#9, HR 0.75): Systemic estradiol used in postmenopausal hormone replacement therapy (HRT) was associated with a 25% mortality reduction in women, driven by skeletal preservation, metabolic homeostasis, and cardiovascular risk reduction (Manson et al., 2017).
- Translational Divergence in Estrogen Stereoisomers: While 17-beta estradiol demonstrates survival benefits in human females, 17-alpha estradiol (a non-feminizing enantiomer) selectively extends median lifespan by up to 19% exclusively in male mice in the NIA ITP (Harrison et al., 2014).
- Estriol Low-Potency Consistency (#8, HR 0.74): Oral/topical estriol—a weaker estrogen metabolite—demonstrated a concordant 26% reduction in all-cause mortality, reinforcing the receptor-mediated nature of estrogenic protection.
- Vagifem Local Formulation Benefit (#7, HR 0.73): Localized vaginal estradiol tablets demonstrated a 27% mortality reduction, suggesting that treating localized postmenopausal urogenital atrophy prevents ascending urinary tract infections and related systemic complications.
- Estraderm Transdermal Delivery (#4, HR 0.67): Transdermal estradiol patches showed a 33% reduction in mortality hazard, avoiding first-pass hepatic metabolism and reducing hepatic pro-thrombotic clotting factor synthesis compared to oral routes.
- Ovestin Vaginal Estriol Replication (#3, HR 0.63): Local vaginal estriol cream demonstrated a 37% mortality reduction, replicating the strong protective signal observed with Vagifem.
- Marvelon Extreme Effect Size (#1, HR 0.18): The 82% mortality reduction observed with Marvelon (ethinylestradiol/desogestrel) is driven by immortal time and healthy user bias in young, reproductive-age women with an extremely low baseline incidence of death.
- Pooled Estrogen Class Robustness: Aggregating all prescription estrogen modalities in women yielded a pooled HR of 0.76 (p = 5e-6), establishing estrogen replacement as the most statistically resilient pharmacological signal in the entire dataset.
- Avaxim Hepatitis A Vaccination (#6, HR 0.71): The inactivated Hepatitis A vaccine was associated with a 29% mortality reduction, reflecting infection prophylaxis and potentially broader non-specific trained innate immunity benefits.
- Revaxis Booster Vaccine Advantage (#2, HR 0.59): The diphtheria, tetanus, and inactivated poliomyelitis booster vaccine demonstrated a 41% mortality reduction, acting as a marker of proactive preventive healthcare utilization and pathogen prevention.
- Lymecycline and the Mitohormesis Hypothesis (#5, HR 0.69): The 31% mortality reduction associated with the tetracycline antibiotic lymecycline is hypothesized to involve low-grade mitochondrial ribosomal inhibition, triggering the mitochondrial unfolded protein response (UPRmt) and mitohormetic resilience.
- SGLT2 Inhibitor Pooled Signal (HR 0.64): Pooled analysis of SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin; n = 563) revealed a 36% all-cause mortality reduction (p = 0.01) despite individual drugs lacking individual sample power (Baigent et al., 2022).
- Canagliflozin ITP Concordance: The human SGLT2 inhibitor signal aligns with NIA ITP results, where canagliflozin extended median male mouse lifespan by 14% via blunting postprandial glucose excursions and attenuating renal/cardiac fibrosis (Miller et al., 2020).
- Metformin Epidemiological Neutrality (HR 1.00): Metformin demonstrated no mortality benefit (HR 1.00), aligning with contemporary clinical analyses showing that metformin does not extend lifespan in non-diabetic populations and fails to replicate longevity claims outside of hyperglycemic control.
- ACE Inhibitor Registry Paradox (HR 1.10): ACE inhibitors exhibited an elevated hazard ratio (HR 1.10), directly conflicting with Level A randomized trials demonstrating a 10% mortality reduction in hypertensive cohorts (Savarese et al., 2013), demonstrating residual confounding by baseline cardiovascular pathology in observational cohorts.
- Critical Evidence Gaps (Rapamycin & Testosterone): Direct human longevity candidates such as rapamycin (mTORC1 inhibitor) and testosterone replacement therapy had insufficient prescription volume (n < 500) to meet inclusion thresholds, remaining unevaluated.
- Prescription Data Limitations: Over-the-counter medication usage, adherence rates, and granular sub-phenotypes were untracked in prescription records, requiring cautious interpretation of raw hazard ratios.
IV. Actionable Protocol (Prioritized)
`========================================================================
CLINICAL EVIDENCE HIERARCHY FOR CANDIDATE GEROPROTECTIVE PROTOCOLS
=========================================================================
[HIGH CONFIDENCE TIER] ──> Level A/B Evidence (RCTs, Meta-Analyses)
[EXPERIMENTAL TIER] ──> Level C/D Evidence (Cohort / Mechanistic / High Safety)
[RED FLAG ZONE] ──> Debunked / Net Harm / Safety Data Absent
==========================================================================
1. High Confidence Tier (Level A/B Evidence)
Interventions validated by randomized controlled trials and meta-analyses for reducing all-cause/cardiovascular mortality in defined clinical indications.
-
Low-to-Moderate Dose Statin Therapy:
- Compound & Dosing: Atorvastatin (10–20 mg daily) or Rosuvastatin (5–10 mg daily).
- Evidence Level: Level A (CTT Collaboration, 2012).
- Clinical Directive: Target Apolipoprotein B (ApoB) and LDL-C reduction using the minimum effective dose. Titration beyond 20 mg yields diminishing lipid-lowering returns while increasing risks of new-onset dysglycemia and transaminitis.
-
SGLT2 Inhibition for Metabolic and Cardiorenal Protection:
- Compound & Dosing: Empagliflozin (10 mg daily) or Dapagliflozin (10 mg daily).
- Evidence Level: Level A (Baigent et al., 2022).
- Clinical Directive: Indicated for type 2 diabetes, chronic kidney disease (eGFR 20–60 mL/min/1.73m²), and heart failure (HFrEF/HFpEF) to lower cardiovascular and all-cause mortality.
-
Menopausal Hormone Replacement Therapy (Timing Hypothesis):
- Compound & Dosing: Transdermal 17-beta estradiol (0.025–0.05 mg/day patch) combined with oral micronized progesterone (100–200 mg/day) for women with an intact uterus.
- Evidence Level: Level A/B (Manson et al., 2017).
- Clinical Directive: Initiate within 10 years of menopause onset or prior to age 60 for vasomotor symptoms and bone mineral density maintenance; transdermal route minimizes hepatic thrombotic risk.
-
Routine Adult Vaccine Series:
- Formulations: Tdap/Td boosters (every 10 years), Hepatitis A/B, and age-appropriate respiratory/shingles immunizations.
- Evidence Level: Level A.
- Clinical Directive: Prevents lethal infectious complications and stabilizes baseline immune homeostasis.
2. Experimental Tier (Level C/D Evidence, Favorable Safety Margin)
Hypothesis-generating interventions with strong mechanistic rationale, animal longevity replication, and low risk of adverse events.
-
Low-Dose PDE5 Inhibition:
- Compound & Dosing: Tadalafil (2.5–5.0 mg orally once daily).
- Evidence Level: Level C (Andersson et al., 2017; Morin et al., 2024).
- Target Mechanisms: Endothelial nitric oxide availability, downstream cGMP-PKG phosphorylation, microvascular perfusion, and suppression of mild pelvic/prostatic inflammation.
- Safety Screen: Absolute contraindication with organic nitrates (nitroglycerin) or soluble guanylate cyclase stimulators due to severe hypotension.
-
Localized Vaginal Estrogen Therapy:
- Compound & Dosing: Vaginal estradiol tablets (10 mcg) or estriol cream (0.1%) 2–3 times weekly.
- Evidence Level: Level B/C.
- Target Mechanisms: Alleviates Genitourinary Syndrome of Menopause (GSM), prevents recurrent urinary tract infections, and preserves pelvic floor tissue architecture with minimal systemic absorption.
3. Red Flag Zone (Debunked / Unfavorable Risk-to-Reward / Safety Data Absent)
Practices lacking safety data, unverified in human longevity trials, or carrying documented toxicity.
-
Chronic Off-Label NSAID Consumption for Geroprotection:
- Status: Net Harm / Toxic (CNT Collaboration, 2013).
- Risk Profile: Chronic use of naproxen, ibuprofen, or high-dose aspirin causes peptic ulcer disease, upper GI hemorrhage, acute renal failure, and elevated major adverse cardiovascular events (MACE).
-
Off-Label Antibiotic Cycling for “Mitohormesis”:
- Status: Safety Data Absent / High Risk.
- Risk Profile: Chronic or cyclical use of tetracyclines (e.g., lymecycline, doxycycline) disrupts the gut microbiome, promotes antimicrobial resistance, and induces photosensitivity and hepatotoxicity without clinical longevity evidence.
-
Metformin for Lifespan Extension in Non-Diabetic, Healthy Individuals:
- Status: Debunked / Neutral.
- Evidence: Human observational registries (Morin et al., 2024) show HR 1.00. RCT data demonstrate that metformin blunts cardiorespiratory fitness gains (VO2 max) and skeletal muscle hypertrophy adaptations in healthy exercising adults.
-
Unmonitored High-Dose Oral Estrogens or Synthetic Progestins:
- Status: Net Harm.
- Risk Profile: Oral synthetic estrogens (ethinylestradiol) carry elevated risks of deep vein thrombosis, pulmonary embolism, and stroke compared to transdermal bioidentical 17-beta estradiol.
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I’m not too excited with the idea of taking another unhealthy medication (different if you have had a previous heart attack or stroke) to “cancel” out the negative effects of the first. It seems overly optimistic (see my other comment just above)
The current Mounjaro pens are single dose. They cannot be split up the way Ozempic pens can be.
I think the every other week strategy is pretty good given the shortages. I go 8 to 9 days on Mounjaro doses so that I can stretch it out and have a pen or two on reserve to wait out the shortages.
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Umm I have patients who split the doses, primarily in California as getting compounded stuff sent to CA is challenge.
Magnified glasses on. 1 mL syringe with plunger fully pulled out, facing upwards. Mounjaro autoinjector, unlock, cap off, with Mounjaro autoinjector facing down, very carefully put opening of 1 mL syringe over the needle, and press the button on the autoinjector.
Your 1 mL syringe now contains just over 0.5 mL (50 units on an insulin syringe).
So if you are using the 15 mg/0.5 mL Mounjaro pen, and you need 5 mg, then 0.16-0.17 mL per dose which is 16-17 units on an insulin syringe. So you have your 3 insulin syringes - wait 2-3 minutes for the foam to go down in the 1 mL syringe then carefully advance the plunger until the mounjaro solution is need the tip of the syringe and stepwise, pull a little into the insulin syringe, then advance the plunger, repeat until you have 16-17 units, do likewise with insulin syringe 2 and 3 …
In this fashion - 3 x 5 mg doses from a 15 mg autoinjector. Naturally, just like Mounjaro - keep the insulin syringes in the fridge.
Anyway - have patients who have been doing this for a long time … it’s quick and easy - but need to take care that plunger is pulled down to 1 mL on the 1 mL syringe to the syringe to accept the solution, and that the needle is in the 1 mL syringe from the autoinjector. I’ve had people mess up these steps and end up simply spraying the Mounjaro onto the surface …
Hope that helps … but it is easy once you’ve done it one time.
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Thanks. I will explore that. In my case, I’m pretty happy just using a single pen and calling it a day. But. . . while I have you, I’m collecting opinions from anyone with experience with these drugs. Please weigh in if you are comfortable offering an unofficial opinion. I’m trying get a pulse on whether it is better to pursue the biggest tolerable dose or Mounjaro or to go with the smallest effective dose.
I’m taking Mounjaro to control blood sugar, not for weight loss. I have an unusual form of diabetes where I have good insulin sensitivity, but seem to produce relatively little insulin. No antibodies for autoimmune response. I switched from Ozempic a few weeks ago, on the hopes that GIP would help me attain a lower average glucose. Indeed, I’m getting slightly better glycemic control with Mounjaro than Ozempic. Now I’m wondering whether a bigger dose would get me an even better response versus whether it is preferable to get by on a smaller dose. I tolerate the drug really well. No side effects. I’m on the 10mg / .5ml dose.
My average blood sugar is around 110 to 115. I would love to get my A1c in the arena of 5.5 or lower.
BTW, when I say I’m collecting opinions, I am under the care of a good primary care doctor and he pays good attention to me. His advice is to stick with a dose for 4 to 8 weeks and then try upping it or lowering it and seeing how results change. So, I’m really just curious to know what anyone else thinks based on experience with other patients.
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