Combining SGLT2 inhibitors — a newer class of diabetes treatments that reduces blood sugar — with older diabetes meds may help to halt the onset of diabetic kidney impairment, according to a mouse study led by Washington University School of Medicine in St. Louis. Dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Canagliflozin) are some of the most commonly prescribed SGLT2 inhibitors (Invokana).

Kidney disease is the largest cause of death in the United States, impacting 37 million people, many of whom are unaware that their kidneys are failing. There is no cure, and the only therapies for end-stage renal disease are dialysis and kidney transplantation.

A mouse study headed by Washington University School of Medicine in St. Louis reveals that combining SGLT2 inhibitors — a newer class of diabetes treatments that reduces blood sugar — with older diabetes drugs may help to halt the course of diabetic kidney impairment.

Dapagliflozin (Farxiga), empagliflozin (Jardiance), and canagliflozin (Canagliflozin) are some of the most commonly prescribed SGLT2 inhibitors (Invokana). Janssen Pharmaceuticals, whose experts cooperated on this study, produces the latter.

Diabetic kidney disease affects roughly 40% of type 2 diabetes patients, resulting in renal failure, cardiovascular disease, and early death. Diabetes, renal disease, and kidney failure are more common in African Americans, Native Americans, and Hispanics than in Caucasians.

Diabetes harms the kidneys by preventing them from filtering waste and extra fluids from the body adequately. Most people don’t recognise they have kidney disease until irreversible organ damage occurs since symptoms including nausea, vomiting, sleep difficulties, and swelling limbs are common and nonspecific.

SGLT2 inhibitors, also known as sodium-glucose cotransporter-2 inhibitors, cause the kidneys to excrete excess sugar from the blood, which is then excreted through urine. Humphreys, who is also the Joseph Friedman Professor of Renal Diseases in Medicine, added, “This family of medications is also very protective for heart disease.”

Although most patients with type 2 diabetes are prescribed only one medicine, the findings of this study show that combination therapy may be more successful since different drug classes target different cell types in the kidney.

The researchers examined how mouse kidneys respond to five diabetes therapy regimens administered to people using mice that had developed diabetic kidney damage. The researchers used single-cell RNA sequencing to look for alterations in the kidneys at the cellular and molecular level as a result of the various therapies. Researchers can use this knowledge to better target certain cells in order to improve medication therapy.

They focused on the impact of three kinds of drugs: SGLT2 inhibitors, angiotensin converting enzyme inhibitors (ACE inhibitors), such as Lisinopril, and Thiazolidinediones (TZD, also known as insulin sensitizers). A common TZD is rosiglitazone.

The study’s first author, Haojia Wu, PhD, an assistant professor in the Division of Nephrology, said, “We structured this study to try to understand how combination medicines affect the kidney differently than single therapies.” “We discovered that each of the distinct classes of medications targeted different cell types, offering a biological justification for combination therapy to help diabetic kidney disease advance more slowly.”

The study discovered that combining SGLT2 inhibitors with Lisinopril showed superior kidney protection than either of the standalone treatments.

SGLT2 inhibitors also appeared to mislead the kidney into initiating a starvation response, similar to how the body slows down its metabolism while fasting for long periods of time, according to the researchers.

This could lower the kidney’s overall energy consumption, allowing it to perform more efficiently and putting less strain on it in the long run, which could explain why this family of medications is so effective,” Humphreys added.

“Treatments for diabetic kidney disease are at an all-time high,” he noted. “Our research adds to the growing body of data that combining medicines has significant benefits for patients.” Such techniques, we believe, should be used in ordinary clinical practise.”

Future observational studies in persons using combo medicines, according to Humphreys, should provide more data.

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