Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally developed to manage type 2 diabetes, have shown impressive protective effects for the heart and kidneys.
Now, new preclinical research suggests that combining SGLT2 inhibition with SGLT1 inhibition may offer even greater benefits—especially for individuals with salt-sensitive hypertension.
In healthy kidneys, SGLT2 reabsorbs about 97% of filtered glucose in the early sections of the proximal tubule, while SGLT1 picks up the rest in the later segment.
In a recent rat study, scientists found that blocking both SGLT1 and SGLT2 worked better than blocking SGLT2 alone for treating high blood pressure caused by too much salt and for preventing kidney damage. The findings will be presented at ASN Kidney Week 2025, held from November 5–9.
Salt-sensitive hypertension is a form of high blood pressure triggered by excess salt intake. It affects nearly half of those with high blood pressure and plays a major role in worsening kidney disease, increasing heart complications, and pushing patients toward kidney failure.
Researchers compared two treatments in rats: dapagliflozin, which selectively inhibits SGLT2, and sotagliflozin, which inhibits both SGLT1 and SGLT2. Both drugs significantly slowed the development of salt-induced hypertension. However, sotagliflozin had even stronger effects.
Specifically, dual inhibition with sotagliflozin led to greater reductions in mean arterial pressure and better protection against kidney injury than dapagliflozin.
It also lowered body weight, increased the amount of sodium and chloride passed in urine, and nearly doubled the amount of glucose excreted—without affecting blood pressure in normal-salt conditions.
Interestingly, neither drug changed overall kidney function. But SGLT2 inhibition did trigger region-specific changes in kidney metabolism. It especially affected fat metabolism and inflammation-related signals in certain kidney areas.
“Our study provides preclinical evidence supporting the expanded use of dual SGLT1/2 inhibitors beyond heart failure and diabetes, extending their potential into hypertension management, particularly in salt-sensitive patients,” said Olha Kravtsova, Ph.D., the study’s lead author from the University of South Florida.
She also emphasized that this research offers a solid starting point for exploring how kidney metabolism varies in different regions. The findings point to fat and inflammation pathways in the kidney as potential new treatment targets for high blood pressure.
These results suggest that future therapies might better control blood pressure and protect the kidneys by using dual SGLT1/2 inhibitors—especially for patients whose high blood pressure is tied to salt intake.
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