Diabetes and Kidney Stones? This Drug Could Help

Diabetes, unfortunately, can cause kidney stones. High blood sugar levels — the signature feature of both type 1 and type 2 diabetes — lead to a significant increase in the risk of kidney stone formation. Kidney stones are well known to be one of the most painful common maladies, and if you’ve ever had one, you’ve probably thought about how to prevent another from forming.

A recent study has some good news for people who experience both diabetes and kidney stones. The evidence now shows that the class of drugs known as SGLT2 inhibitors may significantly reduce the risk of kidney stones.

Kidney Stones & Diabetes

There are multiple types of kidney stones. Diabetes is closely linked with one specific variety, the uric acid stone.

Uric acid is a waste product that naturally circulates through the bloodstream, according to the Cleveland Clinic. It is the job of the kidneys to filter out waste like uric acid and remove it from the body through the urine. But when your body has too much uric acid, the kidneys may be unable to keep up — the uric acid can collect and form crystals. If these uric acid crystals cannot pass out of your body, they may get stuck in the urinary system, causing excruciating pain and other symptoms. Diabetes and related metabolic conditions, such as obesity and metabolic syndrome, appear to raise the acidity of the bloodstream, making uric acid stones more likely to form.

Uric acid “urolithiasis” may be a consequence of insulin resistance, a signature feature of type 2 diabetes. It is less clear to what extent type 1 diabetes triggers kidney stone formation, though at least one study has suggested that type 1 also increases the likelihood of kidney stone formation.

New Evidence

In late January 2024, the medical journal JAMA Internal Medicine published a new study showing that SGLT2 inhibitors could reduce the risk of kidney stone formation in people with type 2 diabetes. The work was a collaboration between Massachusetts area experts in diabetes and nephrology, led by Julie Paik, MD, ScD, MPH.

The study examined the insurance records of over one million American adults with type 2 diabetes. They found that those who had begun using an SGLT2 inhibitor were about 30 percent less likely to experience a kidney stone than those who used alternative glucose-lowering medications. The positive effect took hold very quickly — most patients only participated in the study for about six months.

It’s also worth noting that SLGT2 inhibitors outperformed the blockbuster GLP-1 receptor agonist class, which includes the world’s most hyped drug, semaglutide (Ozempic). Although early evidence suggests that semaglutide can also protect kidney health, the JAMA study shows that it is not nearly as effective at preventing kidney stones. GLP-1 users were about 40 percent more likely to receive treatment for a kidney stone.

Dr. Paik told Diabetes Daily that the results were clinically significant: “The risk of kidney stones in a patient might be one additional consideration for a clinician to take into account when choosing among the different glucose-lowering agents for patients with type 2 diabetes.”

SGLT2 Inhibitors

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are pills that help lower blood glucose levels by stopping the kidneys from reabsorbing the sugar in your bloodstream. Extra sugar leaves the body through the urine. They are approved for use in type 2 diabetes, and are also frequently prescribed off-label for people with type 1 diabetes.

There are four SGLT2 inhibitors available today in the United States:

 Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)

SGLT2 inhibitors lead to improved blood sugar levels and modest weight loss, but diabetes experts are really excited about their ability to protect against cardiovascular and kidney disease. A review of major outcome trials found that drugs in the SGLT2 class have powerful protective effects on kidney health, significantly slowing the decline of glomerular filtration rate (GFR) and the development of macroalbuminuria, two of the signature indications of kidney decline. They do this by improving blood flow reducing scarring and inflammation within the kidneys.

Kidney stones are more than just a short-term misery. Paik said that “in addition to being quite painful, they can cause kidney damage and increase the risk of other sequelae, like urinary tract infections, cardiovascular disease, and fractures.”

Type 1 Diabetes?

Paik declined to speculate on whether SGLT2 inhibitors might have the same effect on people with type 1 diabetes. Though these drugs are not officially approved for use in type 1, they are commonly prescribed off-label to help with glucose control and weight loss. There is encouraging evidence that SGLT2 drugs also protect the kidneys of patients with type 1 diabetes, though they also carry a significant risk of triggering diabetic ketoacidosis (DKA).

 

Uric Acid Stones. Cleveland Clinic. August 19, 2021.

Nerli R et al. Type 2 Diabetes Mellitus and Renal Stones. Advanced Biomedical Research. August 31, 2015.

Kacem B. Study of Urinary Crystals for Type 1 Diabetics. UroToday. 2008.

Paik J et al. Sodium-Glucose Cotransporter 2 Inhibitors and Nephrolithiasis Risk in Patients With Type 2 Diabetes. JAMA Internal Medicine. January 29, 2024.

Groop P et al. Effect of Dapagliflozin as an Adjunct to Insulin Over 52 Weeks in Individuals With Type 1 Diabetes: Post-hoc Renal Analysis of the Depict Randomised Controlled Trials. The Lancet Diabetes & Endocrinology. October 2020.

Danne T et al. International Consensus on Risk Management of Diabetic Ketoacidosis in Patients With Type 1 Diabetes Treated With Sodium–Glucose Cotransporter (SGLT) Inhibitors. Diabetes Care. June 1, 2019.

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