Non-diabetics taking SGLT2 inhibitors (Jardiance, Invokana, etc.)—what is your experience?

#35

Deborah_Hall,

In answer to your question about SGLT-2s and bone remodeling I asked ChatGPT. Keep in mind that you can not have complete trust in this particular AI program which regularly gives me wacky answers. Here is my question, followed by ChatGPT’s answer:

SGLT-2 drugs can cause problems with bone remodeling: Search for evidence of this for each type of SGLT-2 drug. Note whether evidence indicates an increase or a decrease in bone density for each SGLT-2 type. Note whether there could be an increase or decrease in fracture risk due to bone remodeling for each SGLT-2 type. Put data in a table and use the minimum number of words to clearly answer each point.

Evidence is strongest for canagliflozin; for the other SGLT-2 inhibitors, bone effects are generally neutral or uncertain. Class-level meta-analyses show no significant reduction in BMD and no significant increase in fracture risk overall.

SGLT-2 drug Bone remodeling / BMD evidence BMD direction Fracture risk from bone effects
Canagliflozin Most evidence for altered mineral metabolism; some long-term studies reported modest hip BMD loss. CANVAS fracture signal observed. ↓ slight (hip; not consistently all sites) Possible ↑; evidence mixed, not confirmed in later meta-analyses.
Dapagliflozin Studies generally found no effect on bone turnover markers or BMD. ↔ no meaningful change ↔ no clear increase; isolated renal-impairment trial reported more fractures.
Empagliflozin Clinical trials and pooled analyses found no meaningful BMD or fracture signal. ↔ no meaningful change ↔ no increase detected.
Ertugliflozin Limited data; cardiovascular outcomes trial found no significant fracture increase. ↔/unknown ↔ no increase detected.
Sotagliflozin Very limited direct bone-remodeling data. Unknown Unknown; no established signal.
Drug Bottom-line assessment
Canagliflozin Weak evidence for ↓ BMD and possible ↑ fracture risk; strongest concern in class.
Dapagliflozin Neutral BMD; fracture risk generally neutral.
Empagliflozin Neutral BMD; fracture risk neutral.
Ertugliflozin Neutral/insufficient BMD data; fracture risk neutral.
Sotagliflozin Insufficient evidence.

Overall class conclusion: SGLT-2 inhibitors do not appear to decrease BMD or increase fracture risk as a class; concern is mainly limited to canagliflozin, and even that signal remains debated.

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#36

I started Jardiance 12.5 mg with breakfast about 9 months ago. It consistently lowers my post meal glucose spikes and it brought my HbA1C down from 5.7 to 5.4. I notice no side effects except possibly a slight decrease in energy level, but I don’t want to take the time to test that theory.

Yes, glucose in the urine is a very slim potential problem, but highly unlikely for anyone maintaining regular hygiene. Having said that I suggest you look up SGLT-2 inhibitors and Fournier’s gangrene (necrotizing fasciitis of the perineum), a rare but potentially life-threatening infection.

#37

Jay, thank you so much for the information. Looks like empagliflozin might still be something to consider.

#38

Empagliflozin actually raised my glucose levels, slightly. I’m 46, relatively lean (14-15% body fat), and already have pretty low fasting glucose. My fasting glucose taken from blood panels has ranged from 67 to 83 mg/dL since 2023, my A1c has ranged from 5.4 to 5.1 during this time as well. My A1c goes up or down primarily depending on how much I eat and how many carbs I eat; same for my fasting insulin levels, which go low the less carbs I eat. So, I decided to experiment taking 10mg of empagliflozin daily, typically at night for about 90 days. During the last two weeks I put on a Stelo CGM and recorded my glucose values, then stopped taking it, and put on another CGM. I suspected that the empagliflozin was raising my glucose levels already, because when I used a finger prick in the mornings while on it, it was always in the 90s whereas usually its in the 80s.

The results were that empagliflozin did raise my average glucose by about ~4mg/dL, mostly by raising the low end/floor: my average on empagliflozin was 95.76 versus off at 91.95. Comparing the medians gave similar results, and as you might suspect, though, empagliflozin lowered the standard deviation a little bit, 9.70 compared to 11.27 normally. Interestingly, the highs, maximums and upper percentiles were almost identical. So it didn’t do anything to reduce spikes. So it seems to have prevented really low dips overnight, where most of my lower readings (in the 60s and 70s) occur.

To be thorough, I then performed a regression, adjusting for total daily calories and total daily carbohydrates (taken from my Chronometer app), just in case I was eating more while on empagliflozin. To my surprise, I was actually eating slightly more carbs off of it. The nutrition-adjusted efect was slightly larger than the unadjusted effect, about 4.65 mg/dL. Presumably this is due to a counteracting homeostatic effect, where my liver produces more glucose in response.

So for background, at the time I had been on 500mcg of semaglutide weekly and had been taking emiglimin daily, 1,000 mg, once at night also, about half the prescribed dose. These were unchanged though.

My question: are there any plausible benefits to taking something like SGLT2 inhibitors (or other drugs like imeglimin or acarbose) when your blood sugar is already really low? Another question is might these drugs be more effective for people on high carb diets? Right now, I am on a very high protein diet, 150mg to 200g daily out of my 3,000 calories, and usually about 100 grams of carbs. I realize this isn’t recommended by a lot of people, like Valter Longo, etc. But when I used to eat a lot of fruit and breads, my A1c would go up higher, albeit in ‘normal’ range, up to 5.4 for example. So now I’m thinking, perhaps you could get the best of both worlds, by eating healthy complex carbs, while also minimizing their negative effects by taking these drugs. What do you all think? I’ve since stopped taking empagliflozin, but might do an acarbose experiment next. But since my blood sugar is already very low, what biomarkers would I assess to see if they are having any benefit?

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#39

John, if I’ve learned anything from this thread, it’s that you need a robust insulin baseline to harness any longevity value from an SGLT-2 inhibitor. Taking it when your insulin is already depleted is a terrible ROI. Your insulin is the only thing keeping you out of ketosis. If that baseline is already near zero, adding an SGLT-2 inhibitor creates a massive, unbalanced risk. You are trading highly speculative, long-term longevity benefits for the immediate, real-world danger of DKA some have reported. When I receive my Jardiance, I will start with the baby dose, 5 mg. Since I am on OMAD (11th years) and Metformin, I will take it with meal and maintain my fluid balance by incorporating electrolytes i.e., sodium and potassium, throughout the day.

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#40

Whole thread here about SGLT-2 inhibitors and their various benefits, independent or not of their blood sugar lowering abilities: Canagliflozin - Another Top Longevity Drug

Very useful to read. Very briefly :

  • heart failure and cardiovascular protection
  • kidney protection
  • uric acid lowering
  • anti inflammation and anti fibrotic effects

And more.

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#41

A major clinically validated benefit is, perhaps the most critical for us on this forum: Klotho upregulation and preservation through both direct and indirect mechanisms. This is what motivates me to experiment with SGLT-2.

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#42

You humble me. Do you think Jardiance helped you with (stubborn) fat loss?

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#43

Hey Steve… I think my initial weight loss for muscle came with TRT for a year.

Then, I started rapamycin 6 mg weekly… -and after 3 months of weekly 6mg lost 25 pounds of visceral fat… just vanished. DEXA showed no fat there. Body used it.

Veins popped and I can eat non-stop

I think Jardiance is protecting me from my sugar and salt intake. Feeling great :+1: _

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#44

Yes, but it has a double nature. An antioxidant in the blood, it can turn into an oxidant in the cells. High levels are linked to gout, inflammation, and worse.

I use febuxostat to keep my uric acid at 4.5. The stuff I get from India is legit.

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#45

I took 12.5 mg Empagliflozin daily. I started losing weight each week. My body compensated with greater appetite. I switched to Dapagliflozin and this went away. My HBA1C did not change under either treatment. I have not had any noticeable side effects other than sometimes it burns when I pee. I assume there is some increased bacterial count accounting for this.

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#46

And just to add to that:

by nature of the clinical trials available, the best evidence exists for kidney protection and non-ASCVD related heart failure (i.e. heart failure not caused by ApoB/LDL related heart attacks). We got hard clinical outcome data out of RCTs.

For most people in this forum, the heart failure aspect may not be that interesting. The prevalence according to most recent NHANES data for the USA is 1,5% in the general population - reaching up to 13% in the very elderly >80 years of age. But these are almost all people with decades of exposure to known risk factors such as high blood pressure. A person with average blood pressure, not obese etc. has a very low lifetime risk up to age 100.

More interesting for everyone is the kidney protection aspect:

even in people doing everything right (in the “normal” range of things), kidney function is declining by about 50% from mid age around 40 to old age above 80. And there doesn’t seem to be a floor - centenarians experience continued decline, eGFR qualifying for kidney transplants in your regular 60 year olds.

So most people (almost all) in this forum can expect to experience this development. The mechanisms of kidney protections seems plausible, too - essentially reducing wear-and-tear in the kidneys through a mechanism specific for the kidneys. Similar to lowering LDL and blood pressure to very low levels to stop ASCVD.

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#47

…its primary indication of glycemic control in diabetes which can be extended to prevention of prediabetes progression to diabetes (we have studies) and glycemic control in general. For people here this too is useful, as quite a few here have prediabetes (myself included) or are struggling with glycemic control.

Stepping outside of RCT trials and looking at multiple obsevational studies, some pretty large scale, I personally am intrigued by persistent and strong associations with neurological health. I roll the dice with these drugs (empagliflozin in my case) betting on this association being actionable in NDD prevention and/or amelioration. I hope my bet pays off.

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#48

Did you ever get your Cystatin-C checked? It’s an easy add-on and will actually give you a valid measure of eGFR (kidney function). Creatinine is essentially worthless for guys like you and me who resistance train and take creatine every day.

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#49

Creatinine is essentially worthless for guys like us!

Exactly :100:.

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Killing it at 68 years. At the gym now. :laughing:

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#50

@Agetron You’re killing it man. Simply killing it. Great job!!!

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#51

I’ll let you all know in a few months. I started taking dapagliflozin 5mg in the am. Arcarbose 25mg at evening meal and 500mg metformin at bedtime. update; I looked it up after I wrote this. my last eGFR in Dec was 90 but is varies from test to test. somethimes it’s in the low 90’s and sometimes in the high 80’s. Not sure why it would vary so much (67 yr male)

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#52

My uric acid was touching 7, After 1 spoon of Allulose daily it has dropped to 4.7.

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#53

This is interesting. I’ll have to look into it. Thanks.

Well, I looked and it’s too good to be true. Compared to fructose and other sugars, which spike uric acid, allulose does nothing. It neither raises or lowers uric acid, at least at the somewhat modest doses of 25 g. At higher doses, however, allulose can induce a laxative effect. It is not a sugar alcohol, but it acts like one in the gut. When used as a sugar substitute, it can result in a transient reduction in uric acid, but that’s because of the reduction in sugar consumption.

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#54

It makes really good ice cream. Inulin works good for ice cream too. Smooth.

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