#11

So, it’s pick your poison time: high blood glucose or bad sleep (which will give you high blood glucose)? Maybe a third option is called for in this situation. I take metformin.

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#12

Yes - its now the SGLT2 inhibitors work, you pee out the sugar instead of digesting it. Its also why the risk of urinary tract infections is higher; because bacteria in the urinary tract love sugar and can really increase in number (for some people, in some situations).

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#13

Stopping the SGLT2, unless your diabetic will not cause high blood glucose. It isn’t necessarily the SGLT2 that is causing your nocturia. Stop it and see what happens. And, I’ve never seen Fournier’s gangrene in a non diabetic.

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#14

All true, but how many patients do you see taking SGLT2 inhibitors that aren’t diabetic? That number, close to zero I would imagine, is a possible reason why you haven’t seen Fourniers gangrene in a non-diabetic.

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#15

You are correct. Patient count of zero. But to say that Fournier’s would happen in a SGLT2 user would imply that glucosuria is the cause which I don’t think is true.
Btw, although I’ve never seen it, Fournier’s does happen in non diabetics.

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#16

Really? You’re concerned if 13 people out of 135,000 get a side effect? I can’t imagine I’d leave the house much if I was afraid of hazard ratios like that.

Among 138,158 SGLT-2 inhibitor users, there were 13 cases of hospitalization for Fournier gangrene (unadjusted incidence rate, 15.0 per 100 000 person-years) compared with 24 cases (unadjusted incidence rate, 9.7 per 100 000 person-years) among 360 685 DPP-4 inhibitor users, corresponding to an adjusted rate difference of 6.7 excess hospitalizations per 100 000 person-years (95% CI, –2.8 to 16.1 per 100 000 person-years) and an adjusted hazard ratio of 1.73 (95% CI, 0.87-3.42) (Table 2).

Seriously - this is in a sample of largely obese, diabetics who already have a significantly higher risk of the issue (though still low). I’m not a medical professional, but this doesn’t seem to be a concern that I would rationally want to spend a lot of time worrying about.

Diabetes mellitus (DM) is a common comorbidity in Fournier’s gangrene with a higher risk of mortality and longer hospital stays in these patients due to the microvasculature of many soft tissues and organs being affected

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846449/

The main risk factors for Fournier’s gangrene are diabetes, obesity, immunosuppression (such as HIV), alcoholism, smoking, male sex, and the use of cytotoxic drugs [2]. Although many of the associated comorbid risk factors are common diseases, FG is rare. The published literature on its incidence in men and women is quite limited. Therefore, analysis from the US Inpatient Database of 593 civilian hospitals in 13 states in 2001 and 21 states in 2004 report that Fournier’s gangrene occurs in 1.6 of every 100,000 males per year, primarily between 50 and 79 years (3.3 of every 100,000).

The risk of Fournier’s gangrene in healthy people (i.e. you’re not an overweight, smoking diabetic) seems to be much less than 1 in 100,000. If it increases risk slightly while making 99,999 people live 15% longer, I think that is a trade-off most societies would take. Your own risk calculations may vary.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9141785/

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Rapamycin and Skin Abscess infection vulnerability
#17

Yes, gangrene is usually a symptom of serious diabetes. If I were pre-diabetic or non-diabetic, I wouldn’t be worried about it. Although anything is possible.

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#18

Thanks for presenting these data. Fourniers gangrene is not the only side effect of these medications as you know, just one of the most catastrophic when it does occur. I’m a bit biased because I have seen this occur in the hospital where I’m employed.

That said, I didn’t suggest that the OP stop the SGLT2 inhibitor because of this risk. I suggested it due to his self reported problems with waking up to void multiple times a night. Might be worth it to see if his sleep improves off of the drug no?

#19

Just thinking out loud here but if the SGLT2 inhibitor pushes glucose into urine doesn’t that potentially feed any tumours which might be growing in the prostate?

#20

I don’t think the prostate is directly exposed to urine normally, but maybe this could happen if you have a tear in the urethra or if one was urinating while upside down, causing some urine to travel up the vas deferens.

Perhaps your concern is relevant to bladder cancer, but I think the risk of bacterial infection is much more relevant as discussed above. Maybe it would be good to combine a UTI inhibitor like cranberry juice with SGLT2i’s, even if one doesn’t get full blown gangrene, it would be beneficial to limit bacterial growth that can cause inflammation/infection.

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#21

Brilliant, thank you. I understand now :slightly_smiling_face:

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#22

@sluggerT80 you’re still assuming that the Fournier’s is a side effect of the SGLT2. We don’t know if it was causation or correlation. List of Medication side effects are fraught with errors.

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#23

Yes - I definitely experience increased urination when on SGLT2 inhibitors. And yes - it might be worth trying a break to see how sleep improves.

Or perhaps try the lowest dose. The half life is about 12 hours, so you’re still going to be getting some effect even in the evening.

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#24

With all due respect, the FDA has known about this with SGLT2 inhibitors for years. No other class of diabetes medication has this warning. It is a class effect.

That said, I understand it is rare. I wasn’t telling OP to stop the medication due to the risk of Fornier’s. It was for the possibility of him getting better sleep without having to wake up multiple times a night with a urine glucose > 1000.

Do you agree that that level of glycosuria would cause poliura as a result?

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#25

Probably. I couldn’t tell if the op had nocturnal before starting the SGLT2.

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#26

Another side effect of SGLT2’s:

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival

https://www.nature.com/articles/s41416-023-02177-2

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#27

Thank you all for your input. I have stopped the Empagliflozin and will monitor the urine glucose but to answer KarlT’s question, yes I have had this issue for close to 20 years and have not solved the problem. Been to four urologists, had cystoscopy twice (camera sent up urethra… fun), prostate is normal for someone my age, tried multiple medications, botox injections in the bladder, electrical stimulation, etc. When this doc found the glucose in the urine test he said “we have to eliminate this before we go any further”. So I am but I have no belief that this is the issue because I just started taking the Empag a few months ago.

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#28

Sleep apnea makes you get up and pee frequently. When your heart gets stressed it puts out a diuretic that then makes it feel like your bladder is full. You have to get up and pee. This is the main symptom.

The other thing is to not drink anything after about 6:00pm

#29

I don’t have sleep apnea. A little about me… I’m 67, very fit for my age (resistance train 6 days a week plus zone 2 cardio), eat a healthy diet (mostly mediterranean, low carb). I do enjoy a drink with dinner (which I’m sure exacerbates the issue, but even when I don’t drink alcohol I have the problem). We eat dinner early and are usually done by 6.

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#30

It’s a bother for sure. I’ve heard and tried various things. Eat a little salt before bed. Don’t drink fluids after 1pm. Exercise to lose a lot of sweat late in day. I only don’t wake up to pee if I’m dehydrated which I don’t recommend. I do it if I need a good nights sleep. I think the key is figuring out how to go back to sleep after peeing. Good luck.

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