BP Lowering Effects of SGLT2 Inhibitors
September 1, 2014 2 minutes read
Sodium-glucose cotransporter type 2 (SGLT2) inhibitors are the newest class of agents available to treat diabetes. In the United States, only canagliflozin and dapagliflozin are FDA approved. SGLT2 inhibitors work by blocking the receptors in the proximal renal tubules from reabsorbing glucose back into circulation. As a result, glucose is excreted in the urine, calories are lost from the body, and we see not only reductions in plasma glucose and A1c, but reduced body weight and reduced blood pressure (BP).
To date, expert opinion has been that the BP reduction is a direct reflection of the diuresis associated with SGLT2 inhibition, but this continues to be debated. In any case, BP reduction is critical in diabetics, who suffer a greater burden of cardiovascular (CV) disease than non-diabetics and worse outcomes when CV events occur. Currently, less than 50% of diabetics with hypertension have attained BP control.
A meta-analysis of placebo-controlled trials (n = 21 trials) with SGLT2 inhibitors found a mean change in systolic BP of approximately 4 mmHg. While at first glance this might seem small, remember that the patient populations selected for SGLT2 treatment were based on presence of diabetes, not hypertension, so the mean baseline BP levels in these trials would not reach the threshold for the diagnosis of hypertension.
SGLT2 inhibitors do not work to reduce glucose in persons with significant CKD (GFR < 45-60 mL/min) because they are dependent on good glomerular filtration rates to induce meaningful amounts of urinary glucose excretion. It is heartening to see a class of diabetic pharmacotherapy that not only produces improved glycemia, but also is associated with weight reduction and lower systolic BP.
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