SGLT2 Inhibitors exhibit greater BP lowering effect compared to DPP-4 Inhibitors: Study

A recent study published in the International Journal of Molecular Sciences revealed that patients initiating sodium–glucose cotransporter 2 (SGLT2) inhibitors experienced greater reductions in blood pressure, with approximately 2.3% systolic and 2.1% diastolic decreases when compared to propensity score–matched new users of DPP-4 inhibitors. 

Originally developed to reduce hyperglycemia by promoting urinary glucose excretion, drugs like Empagliflozin, Dapagliflozin, and Canagliflozin have already demonstrated cardioprotective and nephroprotective effects. Thus, this study highlight their additional “pleiotropic” actions—most notably on blood pressure, body weight, and lipid metabolism.

Clinical data show that SGLT2 inhibitors consistently reduce blood pressure (BP), although the magnitude of effect varies depending on a patient’s background characteristics and baseline cardiovascular risk. Both systolic and diastolic BP levels decline, with benefits also observed in 24-hour ambulatory BP measurements. These reductions are generally modest but clinically meaningful, particularly in individuals with coexisting hypertension.

This research attribute these BP-lowering effects to several physiological mechanisms. Natriuresis plays a central role, along with osmotic diuresis resulting from glycosuria. Together, these processes decrease plasma volume and vascular resistance. Additional proposed contributors include improvements in endothelial function, reduced arterial stiffness, lower sympathetic nervous system activity, and decreased serum uric acid levels. Body weight reduction may further enhance BP control.

Patients treated with SGLT2 inhibitors typically experience a weight reduction of 1 to 2 kilograms within the first few months of therapy. While the initial decline is largely attributed to glycosuria-induced calorie loss, investigators suggest that more complex metabolic adaptations are also involved.

Fat mass reduction occurs in both visceral and subcutaneous compartments, improving cardiometabolic risk profiles. Emerging research indicates that these agents may promote a process in which energy-storing fat cells adopt characteristics of energy-burning brown fat. This shift may enhance energy expenditure and contribute to sustained weight control beyond simple caloric loss.

SGLT2 inhibitors also produce small but measurable changes in lipid parameters. Reported effects include reductions in triglyceride levels and slight increases in total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol. Although the rise in LDL has prompted scrutiny, the overall lipid profile changes are modest and may reflect shifts toward less atherogenic particle composition.

Overall, the findings reinforce the expanding role of SGLT2 inhibitors in cardiometabolic medicine. Beyond their established benefits in glucose control, heart failure, and chronic kidney disease, these agents appear to exert integrated effects on hemodynamics, adipose tissue biology, and lipid regulation. 

Reference:

Katsimardou, A., Theofilis, P., Vordoni, A., Doumas, M., & Kalaitzidis, R. G. (2024). The effects of SGLT2 inhibitors on blood pressure and other cardiometabolic risk factors. International Journal of Molecular Sciences, 25(22), 12384. https://doi.org/10.3390/ijms252212384