People with BD have a certain ACM, as do people with other morbidities. It’s very hard to group them together with all SGLT2i and try to compare ACMs across all these disparate cohorts.
And also, if you look at ACM itself, what is that composed of? They try to separate cause specific to BD, such as suicide, death from unnatural causes etc., but really we should just look at deaths from “natural causes”, here given as - (RR = 1.90, 95% CI: 1.75–2.06, k = 17).
Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus
https://www.sciencedirect.com/science/article/abs/pii/S0954611124002944
SGLT-2 Inhibitors and the Risk of Chronic Obstructive Pulmonary Disease Exacerbations and Mortality in Chronic Obstructive Pulmonary Disease Patients
The clinical effectiveness of sodium-glucose co-transporter-2 inhibitors on prognosis of patients with chronic obstructive pulmonary disease and diabetes
https://www.nature.com/articles/s41467-025-60582-y
Sodium–Glucose Cotransporter 2 Inhibitor Use and Risk of Liver-Related Events in Patients With Type 2 Diabetes: A Meta-analysis of Observational Cohort Studies
Here is a list of top 10 causes of death in the USA in 2024:
Try to evaluate how many of these are impacted by SGLT2i. Question: should SGLT2i be added to the water supply?
New paper (pay walled), mouse model, apparently shows damage and scarring of distal renal tubules due to the high concentration of glucose being excreted from the kidneys.
Sounds like you should hydrate well if on an SGLT2i - at least you can try to dilute the kidney output. I figured as much anyway.
Interesting paper but one surprising bit: “Empagliflozin induced hyperglucosuria that persisted post-cessation”
This is not something that happens in humans so the results might not be translatable to humans. Even more so as they go against the massive amount of evidence showing SGLT2i renal benefits. Including preclinical literature showing that SGLT2i reduce, not worsen, renal inflammation/fibrosis/EMT pathways. For instance: Renal protective effects of empagliflozin via inhibition of EMT and aberrant glycolysis in proximal tubules - PMC
The paper you linked is in proximal tubules. Has anyone examined empagliflozin’s effects on distal tubules in humans?
Could this be because to date they’ve only been looking at proximal as opposed to distal renal tubules, and/or overall renal function as opposed to zooming in specifically on the distal tubules?
Holly molly are these convos ever scientific where I have no clue what to make of them. I started Empa about year ago on suggestions from these boards and do 1/2 pill =12.5mg per day. Are we still in agreement that SGLT2i are beneficial or should I damn stop all the meds and never look at anything until I’m in my death bed LOL. Btw, I started it more so for benefits to other organs (and hopefully as synergetic to rapa) than to lower my glucose which is a bit high mid 90’s but still within normal range.
@jnorm @Davin8r: it’s true that most papers looked at proximal rather than distal tubules but some did:
Surely the above would have noticed if fibrosis was present?
One point in favor of the 2026 paper: “This study is the first to show that acute empagliflozin treatment induces senescence in distal tubular cells of wild-type mice, but not in diabetic mice. Additionally, the long-term effects of empagliflozin promote senescence, EMT, and renal interstitial fibrosis in the distal tubules of both wild-type and diabetic mice.”
Maybe previous papers only looked at diabetic mice and therefore missed “senescence in distal tubular cells”? However, the second sentence applies to both types. Also, ITP found life extension in wild type with canagliflozin and a Chinese paper replicated the result with empagliflozin (but smaller effect).
It’s also surprising that the 2026 paper did not cite or discuss the three papers above. When you make such an extraordinary claim vs all previous literature, you should discuss it a bit, shouldn’t you?
What about ARBs used either alone or in conjunction with SGLT2i wrt. distal tubular cell impact? I haven’t performed any extensive literature search, but I might try later, time allowing. A very general look at kidneys:
Observations of the Effects of Angiotensin II Receptor Blocker on Angiotensin II-Induced Morphological and Mechanical Changes in Renal Tubular Epithelial Cells Using Atomic Force Microscopy
“Renal fibrosis, characterized by increased extracellular matrix (ECM) accumulation on the kidney parenchyma, is the final common manifestation of chronic kidney disease (CKD), regardless of the primary causes [1, 2]. Previous studies reported that renal tubular epithelial cells (TECs) played an important role in the development of renal tubulointerstitial fibrosis [3]. TECs release chemokines and profibrogenic cytokines and undergo epithelial to mesenchymal transition (EMT) in pathological conditions [4–6]. Therefore, understanding the changes of TECs are important for the prevention and effective treatment of renal fibrosis.”