The ability of sodium-glucose transporter-2 (SGLT2) inhibitors to reduce systolic blood pressure has been recognized ever since this class of drugs was launched for the treatment of type 2 diabetes. However, the mechanisms underlying the improvements in blood pressure (BP) and congestive heart failure outcomes following treatment with dapagliflozin are not fully understood. Therefore, researchers of the State University of New York at Buffalo conducted a study to examine whether dapagliflozin decreases systolic blood pressure and modulates vasoactive factors.

It was a prospective, double-blind and placebo-controlled study of 52 type 2 diabetes patients (T2DM) with HbA1c <8%. Researchers randomly assigned the patients to receive either dapagliflozin 10 mg (n= 26) daily or placebo(n=26) for 12 weeks. They monitored half the patients for 6 hours following their first dose for acute effects on BP. They also measured the levels of angiotensinogen, angiotensin II, renin, aldosterone, endothelin‐1, Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), Cyclic adenosine monophosphate (cAMP), Cyclic guanosine monophosphate (cGMP) and neprilysin in the blood and urine samples. They used circulating mononuclear cells (MNC) to measure the expression of angiotensin-converting enzyme, guanylate cyclase and phosphodiesterase 5 (PDE5).

Key findings of the study were:

• Among 52 patients, 24 and 23 patients receiving dapagliflozin and placebo completed the 12-week study.
• The researchers noted that individuals in the dapagliflozin group had a significant reduction in systolic blood pressure, during a single dose of dapagliflozin at baseline, and also after 12 weeks of the study.
• They found that dapagliflozin suppressed angiotensin II and angiotensinogen (by 10.5 ± 2.1 pg/mL and 1.45 ± 0.42 μg/mL, respectively) and increased ANP and cGMP (by 34 ± 11 pg/mL and 29 ± 11 pmol/mL, respectively) compared to the placebo group.
• They also found that the cGMP levels also increased acutely following a single dose of dapagliflozin.
• They observed that dapagliflozin also suppressed PDE5 expression by 26 ± 11% in MNC.

The authors concluded, "Dapagliflozin administration to T2DM resulted in both acute and chronic reduction in systolic BP, a reduction in vasoconstrictors and an increase in vasodilators. These changes may potentially contribute to its anti‐hypertensive effects and its benefits in congestive cardiac failure."

For further information:

https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14377