We file GLP-1s under “diabetes drugs” or “weight-loss drugs.” Both labels are true. But data from the last 24 months show that these are kidney drugs.
“Picture the kind of patient most of us see every week. They have type 2 diabetes (T2D) and a BMI in the mid-30s. They’re on metformin and an angiotensin II receptor blocker (ARB), and their estimated glomerular filtration rate (eGFR) is around 52 mL/min/1.73 m². Their urinary albumin-to-creatinine ratio has been climbing for 3 years. A1c is at goal. They feel fine. Five years ago, we’d tell the patient to keep doing what they’re doing. Today, that advice is wrong. We have a drug class that we were not reaching for, but we should be:”
That’s all wonderful. But every drug needs to be matched to the patient. If for example we have a patient with cancer and the cancer harms the kidneys as a side effect, then a medication X that helps with the cancer can also help the kidneys. Do we at that point announce that the cancer drug X is a kidney drug? And then - continuing with this scenario - if there is an actual kidney drug Y which when administered to that cancer patient somewhat slows down the kidney decline, do we now announce that the cancer medication X is a better kidney drug than Y because X reverses the kidney damage while Y only slows down the decline?
My point here is that we must be cognizant of what we are looking at in drawing any conclusions. If we are dealing with massively obese and/or diabetic population with compromised kidney function then that is a very specific population. There, perhaps a GLP-1RA results in all sorts of benefits including weight loss and blood sugar control and a very nice recovery of GFR in kidneys that are spilling protein. What do we conclude here? That these are fantastic kidney drugs? Perhaps they are - what we can show is that in that specific population, reta has a very good effect on the kidneys… whether directly or as a result of affecting something upstream (and so the kidneys are “accidental” beneficiaries), we can clearly establish kidney benefis.
Now that’s fantastic for that population. A more difficult question is what does that mean for your average biohacker who is not overweight, does not suffer from diabetes, already has excellent kidney function (probably a significant percentage of the readers of this site). Would taking reta for such a person provide some additional protection for the kidneys, or be some kind of preventative in decline of kidney function? Are these “kidney drugs” for such people?
This is where SGLT2i might be of interest. This exact concern was raised about SGLT2i when it was discoverd that these drugs significantly slowed down kidney decline in diabetics with kidney disease. Does that only work for diabetic kidneys? And then, fortunately, we had studies that showed that even in patients who didn’t have diabetes, their kidneys also benefitted from SGLT2i to a similar degree. So we have at least a partial answer in the case of SGLT2i and kidneys - these do appear to likely be “kidney drugs”. Now, what if SGLT2i are like the drug Y in the scenario described above - “true” kidney drugs that “merely slow” the decline of kidney function - although if you start off with kidneys that are completely healthy, maybe that’s as good as it gets; we can posit that reta will somehow boost the kidney function even more, so better than already excellent, but that seems unlikely - more likely seems that in a sick population (as decribed) reta is super helpful. And maybe reta does nothing for fully healthy kidneys - who knows.
I’m not claiming anything about GLP-1RA vs kidney function one way or another. I’m just cautious in pronouncing these drugs as “kidney drugs” in general - it’s possible that they are kidney drugs in a very specific population, but not otherwise. I guess we can wait for more studies - given how widely they are used, far outside of their original indication, we should have some answers fairly soon. The variety of people on GLP-1RA is far greater than SGLT2i, so we can actually end up knowing far more about these drugs effectiveness in various populations than we will ever know about SGLT2i. I look forward to more data!
It certainly would be nice to have another resource for kidney protection, especially if they work along a different MOA than other drugs such as SGLT2i.
Many of the renal benefits demonstrated with GLP-1 agonists have occurred in overweight populations with diabetic kidney disease and significant albuminuria. It does not apply to everyone though. As an example, with bmi 19.5, no diabetes, no albuminuria, I would not benefit even though I do have CKD (due to transplanted kidney).