Sodium-glucose cotransporter-2 inhibitors (SGLT2i) lower blood pressure (BP) and provide cardiovascular protection, but whether they modify the BP response to sodium intake in humans has not been explored. In an open-label, non-randomized study published in Cardiovascular Diabetology, 26 patients with type 2 diabetes (14 receiving SGLT2 inhibitors and 12 controls) completed controlled dietary sodium phases to evaluate the salt sensitivity of BP.

Participants underwent two sequential 7-day periods consisting of a very-low-sodium background diet supplemented with either high sodium (+4,800 mg/day) or low sodium (+1,200 mg/day). The median change in 24-hour systolic BP between high and low sodium intake was +5.6 mmHg in controls (IQR 2.0–20.3; p=0.005) compared with −1.2 mmHg in the SGLT2 inhibitor group (IQR −3.6 to 4.2; p=0.594), with a significant between-group difference (p=0.007). Diastolic BP changes followed a similar pattern (+4.6 [1.3–9.8] mmHg vs −1.2 [−3.1–1.4] mmHg; p = 0.002).

During high sodium intake, postprandial natriuresis was greater in the SGLT2 inhibitor group (55.0 [28.3–126.6] µEq/min vs −0.7 [−148.6–109.0] µEq/min; p = 0.049), and postprandial diuresis was also higher (0.52 [0.10–1.18] ml/min vs −0.21 [−0.58–0.45] ml/min; p = 0.041). During low sodium intake, renin and aldosterone increased in controls but not in treated participants. Hydration and glycosuria were unchanged and unrelated to natriuretic responses.

These findings describe associations between SGLT2 inhibitor therapy and a smaller BP difference between high and low sodium intake in patients with type 2 diabetes.