Diabetes and your kidneys: what the big trials show about the four pillars of kidney protection

Diabetes is the leading cause of kidney failure in the United States. The encouraging news is that, over the last several years, large studies have given kidney doctors more tools to slow kidney damage than ever before.

Welcome to the November issue of Kidney Health Monthly. Last month we walked through Medicare Open Enrollment and how to keep your kidney care team covered for next year. This month we turn from the insurance paperwork to the medicines themselves, because November is National Diabetes Month, and diabetes and the kidneys are closely tied.

Here is why it matters. According to the American Diabetes Association, kidney disease caused by diabetes is the leading cause of kidney failure in the United States. The National Institutes of Health estimates that about 1 in 3 adults with diabetes has kidney disease, and most people feel nothing at all in the early stages.

That can sound worrying, so here is the hopeful part. Over the last several years, a series of large, carefully run studies have shown that several kinds of medicine can slow kidney damage in people with diabetes. Kidney doctors sometimes call them the “four pillars” of kidney protection. This article is a plain-English tour of what those studies found, who was in them, and what it may mean for you.

A quick word before we start: this is general education, not a prescription. Every medicine below has its own side effects and reasons it may or may not fit a particular person. Please do not start, stop, or change any medicine on your own. Bring your questions to your KHC nephrologist or your diabetes doctor.

The short version

If you remember only three things from this article, make them these:

• Ask for two tests every year: a urine albumin test (UACR) and a kidney blood test (eGFR). They are how kidney disease from diabetes is found early.
• There are now four kinds of medicine shown in big trials to help protect the kidneys in diabetes: ACE inhibitors or ARBs, SGLT2 inhibitors, finerenone, and GLP-1 medicines such as semaglutide.
• Not everyone needs all four. Your doctor chooses based on your tests, your other health conditions, your blood work, and your goals.

First, the two yearly tests

Before any talk of medicines, there is a simple step that comes first: finding out how your kidneys are doing. The American Diabetes Association’s 2026 Standards of Care recommend checking two things at least once a year for everyone with type 2 diabetes, and for people who have had type 1 diabetes for 5 years or more:

• UACR (urine albumin-to-creatinine ratio). A small urine sample that checks for albumin, a protein that should mostly stay in your blood. Albumin leaking into the urine is often the earliest sign that diabetes is affecting the kidneys. You can read more in our article on what protein in the urine means.
• eGFR (estimated glomerular filtration rate). A blood test that estimates how well your kidneys filter. Our guide to eGFR explains the numbers.

The ADA notes that changes in the urine albumin test can show up before the eGFR changes. That is why the urine test matters so much: a blood test alone can miss early kidney disease. If you already have kidney disease, the ADA recommends checking these tests more often, from 1 to 4 times a year depending on your stage.

Doctor’s tip: many people have had an eGFR without ever having a UACR. At your next diabetes visit, ask: “Have I had my urine albumin checked this year?”

The foundation under the pillars

Pillars need a solid floor. A joint report from the American Diabetes Association and KDIGO (Kidney Disease: Improving Global Outcomes, the international group that writes kidney guidelines) describes kidney protection as medicines layered on a foundation of healthy lifestyle. That foundation includes not smoking, staying active, eating well, managing blood sugar, and controlling blood pressure. For most people with diabetes and kidney disease, the ADA recommends a blood pressure goal below 130/80, if it can be reached safely. Our article on high blood pressure and kidney damage explains why.

Now, the four pillars.

Pillar 1: ACE inhibitors and ARBs

What they are: Blood pressure medicines that, in people with diabetes and kidney disease, also help protect the kidneys. ACE inhibitor names usually end in “-pril” (such as lisinopril), and ARB names usually end in “-sartan” (such as losartan).

What the studies showed: Two landmark trials published in 2001 studied people with type 2 diabetes and kidney disease:

• In RENAAL (about 1,500 people), losartan lowered the risk of the main kidney outcome by 16 percent compared with placebo, and lowered the risk of reaching kidney failure by 28 percent.
• In IDNT (about 1,700 people with high blood pressure), irbesartan lowered the risk of the main kidney outcome by 20 percent compared with placebo.

In both trials, the kidney benefit was more than blood pressure lowering alone would explain.

Who they are for: The ADA recommends an ACE inhibitor or an ARB for people with diabetes and high blood pressure who have albumin in the urine, and strongly recommends it when albuminuria is high or eGFR is below 60. Your doctor usually raises the dose to the highest amount you can comfortably take. The ADA also says these medicines are not recommended just to prevent kidney disease in people with diabetes whose blood pressure, urine albumin, and eGFR are all normal.

What to know: Your doctor will check your potassium and kidney function after starting. A small rise in creatinine (a waste product measured in the blood) can be expected at first, and the ADA notes that a rise of up to about 30 percent is not, by itself, a reason to stop. That is a judgment for your doctor, not something to decide at home.

Pillar 2: SGLT2 inhibitors

What they are: Pills that were first developed to lower blood sugar by helping the kidneys release extra sugar into the urine. Researchers then discovered that they protect the kidneys and heart in ways that go beyond blood sugar. Examples include canagliflozin, dapagliflozin, and empagliflozin.

What the studies showed:

• CREDENCE (2019) studied about 4,400 people with type 2 diabetes and kidney disease who were already taking an ACE inhibitor or ARB. Canagliflozin lowered the risk of the main kidney and heart outcome by 30 percent, and the risk of kidney failure by 32 percent, compared with placebo. The trial was stopped early because the benefit was clear.
• DAPA-CKD (2020) studied about 4,300 people with kidney disease, with or without diabetes. Over about 2.4 years, the main outcome (a large drop in kidney function, kidney failure, or death from kidney or heart causes) happened to 9.2 percent of people taking dapagliflozin compared with 14.5 percent taking placebo. The benefit was similar whether or not people had diabetes.
• EMPA-KIDNEY (2023) studied about 6,600 people with a wide range of kidney disease, again with or without diabetes. Empagliflozin lowered the risk of kidney disease getting worse or death from heart causes by 28 percent compared with placebo.

Who they are for: The ADA recommends an SGLT2 inhibitor with proven benefit for people with type 2 diabetes and kidney disease. It can be started when eGFR is 20 or higher and can be continued until kidney failure. Because these medicines also work in people without diabetes, you may hear about them for other kinds of kidney disease too.

Pillar 3: Finerenone

What it is: A once-daily pill in a newer class called nonsteroidal mineralocorticoid receptor antagonists (that is a mouthful, so many people just say “finerenone”). It is a different kind of medicine from the other three pillars, and it was studied as an add-on to an ACE inhibitor or ARB.

What the studies showed: Two companion trials studied people with type 2 diabetes and kidney disease who were already on the highest tolerated dose of an ACE inhibitor or ARB:

• FIDELIO-DKD (2020, about 5,700 people, mostly with more advanced kidney disease) found that finerenone lowered the risk of the main kidney outcome by 18 percent compared with placebo, and also lowered the risk of heart problems.
• FIGARO-DKD (2021, about 7,400 people, including many with earlier kidney disease) found a 13 percent lower risk of heart events, mainly from fewer hospital stays for heart failure. In this trial, the kidney outcome leaned in favor of finerenone but did not reach statistical significance on its own.

What to know: The main side effect to watch is a high potassium level. In FIDELIO-DKD, 2.3 percent of people on finerenone stopped the medicine because of high potassium, compared with 0.9 percent on placebo. That is why your doctor checks potassium before starting and with follow-up blood work. The ADA recommends this kind of medicine for people with kidney disease and albuminuria when their kidney function and potassium allow it.

Pillar 4: GLP-1 medicines (semaglutide)

What they are: Diabetes medicines that lower blood sugar and, as researchers have found, can also protect the heart and kidneys. Semaglutide is one well-known example.

What the study showed: The FLOW trial, published in the New England Journal of Medicine in 2024, was the first large trial designed specifically to test a GLP-1 medicine on kidney outcomes. It studied about 3,500 people with type 2 diabetes and kidney disease, who took a once-weekly 1 mg semaglutide injection or a placebo injection for a median of about 3.4 years. Semaglutide:

• lowered the risk of major kidney disease events by 24 percent,
• lowered the risk of death from heart causes by 29 percent, and
• slowed the yearly decline in eGFR.

The trial was also stopped early at a planned check because the benefit was clear.

Who they are for: The ADA’s 2026 Standards now recommend a GLP-1 medicine with proven benefit for people with type 2 diabetes and kidney disease, to slow kidney disease and lower heart risk.

How to read these numbers without getting the wrong idea

A few honest cautions, because we never want to oversell:

• “Percent lower risk” is a comparison, not a guarantee. In DAPA-CKD, for example, a “39 percent lower risk” meant the main outcome happened to about 9 in 100 people on the medicine versus about 15 in 100 on placebo. That is a real and meaningful difference, but the medicine did not prevent every problem.
• Who was studied matters. CREDENCE, FIDELIO-DKD, FIGARO-DKD, and FLOW all studied people with type 2 diabetes and kidney disease. If you have type 1 diabetes, your doctor will talk with you about what the evidence does and does not show for you.
• The pillars stand together. In nearly all of these trials, people were already taking an ACE inhibitor or ARB. The newer medicines were tested as add-ons, not replacements.
• Every medicine has trade-offs. Side effects, other health conditions, other medicines, pregnancy plans, and cost all matter. The ADA specifically advises that some kidney-protecting medicines should be avoided in pregnancy, so tell your doctor if you are planning a pregnancy or could become pregnant.
• Guidelines keep changing. The KDIGO 2022 diabetes guideline is still the current version, and KDIGO is finishing a 2026 update after a public review of the draft. We follow these changes so you do not have to.

From our physicians

We chose diabetes for November because it is the story we see most often in our clinics. Many of our patients come to us after years of living with diabetes, and many of them never had a urine albumin test until their kidney function had already dropped.

What has changed in the last few years is real, and it is worth celebrating. As recently as 2019, the CREDENCE researchers wrote that few effective long-term treatments were available for kidney disease in type 2 diabetes. Today, there is strong evidence for four pillars. For many patients, combining these medicines, along with good blood pressure and blood sugar control, can meaningfully slow kidney damage.

But more medicine is not automatically better medicine. Some patients need all four pillars; some need one or two; some have reasons not to take a particular one. Our job is to look at your tests, your blood work, your other medicines, and your goals, and to build a plan with you. That is a conversation, not a prescription you find on the internet.

So here is what we are asking this November. If you have diabetes, find out whether you had a UACR and an eGFR this year. If you have not, ask for them. If your results show kidney disease, ask your doctor which of the four pillars might fit you, and whether you should see a nephrologist.

Questions to bring to your next visit

• “Have I had a urine albumin (UACR) and an eGFR test in the last 12 months? What were my results?”
• “What stage is my kidney disease, if I have it?”
• “Am I on an ACE inhibitor or ARB? Is it at the right dose for me?”
• “Would an SGLT2 inhibitor, finerenone, or a GLP-1 medicine make sense for me? Why or why not?”
• “What side effects should I watch for, and what blood work will I need?”
• “Which of my medicines should I pause if I get sick, and who should I call?”

Patient resources

• Learn the language of your lab results: what protein in the urine means and what eGFR is.
• Understand where you are: the stages of kidney disease.
• Blood pressure matters too: how high blood pressure damages the kidneys.
• From the National Institutes of Health: the NIDDK’s page on diabetic kidney disease is written for patients and families.

Let’s protect your kidneys together

If you have diabetes and want to know how your kidneys are doing, or you would like to talk through which kidney-protecting medicines might fit you, we are here to help. Book an appointment with a KHC nephrologist, and bring your latest lab results and your list of medicines.

This article is for general education and is not a substitute for personalized medical advice. Talk with your doctor or nephrologist about your specific situation.