Sorry wrong is not correct but a 2011 study that isn’t in DrugAge might be irrelevant. Here it’s a non-peer reviewed abstract report. If the result was so good, surely they would have published it?
Actually “Wrong” was probably the correct assessment:
Prior to this rigorously designed study conducted by the Interventions Testing Program, a 2011 report documented that glycine supplementation could enhance longevity in male Fisher 344 rats (Brind et al., 2011). Although glycine at different doses was reported to extend median lifespan by up to 28.4% and maximum lifespan by up to 30.8%, an analysis using the Wang/Allison method (Wang et al., 2004) found that maximum lifespan was only significantly extended by an 8% dose (Miller et al., 2019).
https://www.sciencedirect.com/science/article/pii/S1568163723000818
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The rat study was the basis for the ITP testing in mice. If the ITP team had seen no merit in the findings, they likely would not have prioritized glycine for formal testing. Although the subsequent ITP study was more rigorously designed and conducted across three independent testing sites, it was performed in mice, so it does not invalidate the earlier rat results. Moreover, rats are a valuable model for gerontological research because they are larger, have longer lifespans than mice, and often show stronger physiological parallels to humans. For example, cardiovascular and renal function. I did specify 8% glycine above.
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On the glycine discussion: among those of European descent, I believe 10-11% are BHMT-08 (rs651852 (A,A), as I am. This genotype may want to consider modifying its glycine and several related supplement parameters. I found the topic to be a deep dive contingent on so many specific related issues that it is better undertaken by the individual rather than posting a generic analysis here.
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Henagliflozin has shown some impressive benefits. I have been trying to obtain some for testing, but it only seems to be available in China. The drug shown in the chart is another “flozin”. Any ideas ?
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I agree. Henagliflozin does not seem to be available outside of China… unfortunately.
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Adding NAC to Glycine could be an entirely different story. Possible multiplier in a major way.
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The proven benefits for dapagliflozin and empagliflozin and waaaaaaaay better than one unreplicated Chinese paper showing benefits for henagliflozin. If correct, it is also likely to be a class effect.
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Wait, shouldn’t we be analyzing the drug itself? As a novel SGLT2 inhibitor , henagliflozin innovatively incorporates a fluorine atom into its structure and utilizes an L-proline co-crystal formulation. Moreover, in terms of both glucose-lowering and blood pressure-lowering efficacy, henagliflozin consistently ranks in the top two. True, it currently lacks cardiovascular outcome trials , but that’s simply because it’s a new drug. Furthermore, henagliflozin can significantly extend telomere length, and its anti-aging mechanisms are already well-established, so I won’t belabor the point here. Price-wise, it is also the most expensive per milligram. Clearly, this is one of the top drugs that anyone focused on anti-aging should be taking.
Furthermore, claiming it ‘lacks replicate validation’ is simply inaccurate. Henagliflozin is already backed by multiple clinical studies, and a recent paper detailing its ability to extend telomere length was published in a Cell sister journal.
Glycine might be a minor improver of lifespan, but it’s honestly really great for sleep, which is the main reason I take it. I found it increases the amount of slow wave sleep I get by about 20 minutes, up to a total of 2 hours on average, and that’s pretty good overall.
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I meant that unreplicated Cell paper. Half of papers are fraudulent/erroneous, so I take everything with a pinch of salt.
Anyway henagliflozin might end up being better than dapagliflozin and empagliflozin but as of today the best data we have is for those two.
Hopefully a team will look at telomere length extension in other SGLT2i.
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To contextualize henagliflozin within the broader SGLT2i landscape, its selectivity profile places it among the highly selective “pure” SGLT2 inhibitors, sitting slightly below empagliflozin but above dapagliflozin.
| Drug Molecule | SGLT2 IC50 (nM) | SGLT1 IC50 (nM) | Selectivity Ratio (SGLT2 vs SGLT1) | Primary Clinical / Structural Feature |
|---|---|---|---|---|
| Empagliflozin | 3.1 | ~8,300 | ~2,700-fold | Highest selectivity among major FDA-approved agents; robust CV/renal data. |
| Ertugliflozin | 0.88 | ~1,900 | ~2,200-fold | Highly potent absolute SGLT2 affinity at sub-nanomolar levels. |
| Henagliflozin | 2.38 | 4,324 | ~1,816-fold | Comparable to top-tier selective agents; minimal intestinal SGLT1 cross-inhibition. |
| Dapagliflozin | 1.2 | ~1,400 | ~1,200-fold | First approved highly selective C-glucoside archetype. |
| Canagliflozin | 2.2 | ~550 | ~250-fold | Low selectivity; cross-inhibits intestinal SGLT1 to delay local glucose absorption. |
| Sotagliflozin | ~1.8 | ~36 | ~20-fold | Intentionally designed dual SGLT1/2 inhibitor; alters proximal gut glucose dynamics. |
As mentioned, the drug is too young to have rigorous CV data, but some interesting studies are underway.
1. Myocardial Infarction and Infarct Size Resolution
A randomized, controlled clinical trial (NCT06187727 ) has been tracking henagliflozin’s direct impact on acute cardiac injury. The study evaluates 240 patients presenting with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI).
- The Endpoint: Patients receive henagliflozin or placebo for 6 months post-PCI. Investigators are measuring dynamic changes in myocardial enzymes, NT-proBNP, and echocardiographic variables to determine if early SGLT2i intervention minimizes definitive infarct size and mitigates adverse post-ischemic left ventricular remodeling.
2. Tissue-Level Myocardial Remodeling via Cardiac MRI
Another highly targeted study (NCT06059287 ) directly compares henagliflozin against metformin in obese type 2 diabetic cohorts over 24 weeks.
- The Endpoint: This trial bypasses broad clinical event tracking in favor of high-resolution Cardiac MRI protocols . It tracks structural changes at the tissue level, specifically mapping myocardial morphology, ejection fraction, and changes in myocardial fibrosis—a key driver of diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF).
3. Exploratory MACE Tracking in Prediabetes
The largest prospective trial evaluating henagliflozin’s broader vascular impact is a large-scale prediabetes trial (NCT06448130 ), which initiated enrollment across 50 Chinese medical institutions.
- The Endpoint: While the primary goal of this 984-patient study is evaluating the rate of normoglycemic remission over a 24-month horizon, the investigators have integrated tracking of long-term macrovascular and microvascular complications, including exploratory MACE rates, as secondary outcomes.
Relaxing standards a bit, the drug’s vitro selectivity profile and its pharmacodynamic structure are almost identical to empagliflozin. This suggests its cardioprotective actions will fall in this general area.
The company has not applied for US FDA approval and indications are that there is no interest in doing so. Given market conditions and possibly near duplication/overlap, I can understand the position.
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I think the Hena study was well documented:
https://www.reddit.com/r/ketoscience/comments/1napiw4/effect_of_henagliflozin_on_aging_biomarkers_in
Larry Cobb
I live in China. Currently, I am trying to use henagliflozin for anti-aging purposes, taking a daily dose of 5 milligrams.
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On henagliflozin and telomeres, @Kelman mentioned there: “Why would placebo group have a 65% increase in telomere, that is huge? and how was it measured?”
Wdyt @Cole?
This is because both groups of participants received lifestyle interventions, including diet control, regular exercise, and overall healthy habits. But even so, the telomere length in the henagliflozin group was still significantly longer than in the control group. I think that really speaks volumes. For us biohackers who already stick to a healthy lifestyle, this makes it an absolutely top-tier drug. Of course, empagliflozin is also an excellent anti-aging drug, with practically flawless performance in its cardiovascular outcome trials.
For telomere measurement, they used qPCR. Its reliability is relatively mediocre—while it isn’t state-of-the-art, it remains the most widely used method. Currently, the most advanced technique is arguably TeSLA.
I accept this paper, warts and all.
I’m sorry I didn’t read your whole response, but the telomere growth rate in the control group was actually 6.67%. Anyway, I support people taking whatever medications they want to take.
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Indeed @Kelman: the paper says 65.57% of placebo participants had any increase in measured leukocyte telomere length but the placebo arm’s increase was around +6–7%, not +65%. The henagliflozin arm was roughly +15%, with an incremental effect over placebo of about +0.06 T/S units.
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Longitudinal changes in leukocyte telomere length and mortality in elderly Swedish men
TL attrition did not predict all-cause or cancer mortality, but we found a 60% decreased risk for cardiovascular mortality in those who shortened their telomeres.
So is telomere lengthening the right metric?
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