SGLT2 Inhibitors vs. DPP4 Inhibitors: Study reveals new benefits of SGLT2i for prevention of hypertension

In the realm of hypertension management, the emergence of novel pharmacotherapies has sparked interest in their comparative effectiveness. Among these, sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have gained prominence for their potential benefits beyond glycemic control.

The analysis used a nationwide large-scale health check-up and insurance claims dataset, including approximately 20,000 patients with diabetes, and compared the subsequent risk of hypertension development between SGLT2i and DPP4i users after propensity score matching. The administration of SGLT2 inhibitors was associated with a decreased risk of developing hypertension compared with DPP4i administration

"To our knowledge, this is the first study to demonstrate the possible advantage of SGLT2 inhibitors in incident hypertension using a large-scale epidemiological database," the researchers wrote.

SGLT2 inhibitors act by inhibiting renal glucose reabsorption, leading to glycosuria and natriuresis. Beyond glycemic control, they exhibit favorable effects on cardiovascular and renal outcomes. Conversely, DPP4 inhibitors enhance insulin secretion while reducing glucagon levels, primarily targeting glycemic control by inhibiting the degradation of incretin hormones.

Although several randomized clinical trials (RCTs) have reported the potential benefit of SGLT2 inhibitors in reducing blood pressure (BP), whether SGLT2i can reduce incident hypertension is unknown. Therefore, Hidehiro Kaneko, The Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan, and colleagues analyzed individuals with diabetes who were newly prescribed SGLT2i or DPP4i in a large-scale epidemiological database.

The primary outcome was the incidence of hypertension. To compare the subsequent development of hypertension between the SGLT2i and DPP4i groups, a propensity score matching algorithm was employed. After propensity score matching, 5708 well-balanced pairs of SGLT2i and DPP4i users were identified.

The findings of the study were as follows:

• SGLT2i administration was associated with a reduced risk of hypertension (HR 0.91).
• The advantage of SGLT2i use over DPP4i use for incident hypertension was generally consistent in several sensitivity analyses, and subgroup analyses revealed that SGLT2i use was significantly associated with a lower risk of hypertension in men, patients with baseline HbA1c of <7.5%, and baseline systolic blood pressure ≥127 mmHg.

In conclusion, in real-world practice, there was a reduced risk of developing hypertension in individuals with diabetes who were newly prescribed SGLT2i compared to those who were newly prescribed DPP4i.

The study findings shed light on the new benefits of SGLT2 inhibitors as a hypertensive preventive medication.

Reference:

Suzuki, Y., Kaneko, H., Okada, A., Komuro, J., Fujiu, K., Takeda, N., Morita, H., Ako, J., Nishiyama, A., Yano, Y., Ieda, M., Node, K., Yasunaga, H., & Komuro, I. (2024). Comparison of incident hypertension between SGLT2 inhibitors vs. DPP4 inhibitors. Hypertension Research, 1-8. https://doi.org/10.1038/s41440-024-01649-z