A modern drug originally developed for the treatment of diabetes, empagliflozin, may, in the right combination, also help people with high blood pressure who do not have diabetes. A new study from IPHYS, published in the journal Biomedicine & Pharmacotherapy, shows that a well-chosen combination, in this case blood-pressure-lowering drugs together with empagliflozin, can improve fat and sugar metabolism, reduce inflammation and decrease fat accumulation in organs, thereby protecting the heart and other organs from damage.
Empagliflozin belongs to the modern antidiabetic drugs known as gliflozins and is commonly used in patients with type 2 diabetes. It lowers blood sugar levels by promoting its excretion in the urine and has a mild diuretic effect. “Empagliflozin was originally developed to treat diabetes. We had already shown that it protects the heart and kidneys, even in experimental animals that do not suffer from diabetes. We have now investigated how this drug interacts with other medicines commonly used to lower high blood pressure. For our research we used an animal model of hypertension without diabetes,” explains Ivana Vaněčková, corresponding author of the study and Head of the Laboratory of Experimental Hypertension.
Which Combinations the Scientists Tested
The scientists used a special experimental model of hypertensive rats carrying the Ren-2 gene, in which high blood pressure is linked to mechanisms similar to those in some patients with severe hypertension. The animals first received either a modern targeted treatment with an ACE inhibitor (trandolapril), which blocks the renin–angiotensin system, or an older type of combination treatment, so-called “triple therapy” (hydralazine, hydrochlorothiazide, reserpine). After four weeks of this treatment, both groups additionally received empagliflozin, which was administered for a further two months. The researchers monitored body weight, fat and sugar metabolism, kidney and heart function, and also signs of inflammation.
When the Combination Helps: Empagliflozin + Trandolapril
In the group treated with trandolapril, adding empagliflozin brought a number of beneficial changes, particularly with regard to sugar and fat metabolism. At the same time, empagliflozin in this combination slightly reduced blood pressure and the levels of inflammatory markers in the blood. A completely different picture emerged in the animals treated with the older triple combination of antihypertensives, where adding empagliflozin led to a worsening of glucose tolerance as well as insulin sensitivity. In this group, deterioration of kidney function was also observed. The study therefore highlights that not every drug combination is safe and beneficial.
Significance for Medicine
The study supports the current trend of prescribing gliflozins not only to patients with diabetes, but also to people without diabetes who have high blood pressure and therefore an increased cardiovascular risk. The results show that the benefit of empagliflozin in patients without diabetes depends greatly on the antihypertensive treatment with which it is combined. At the same time, it warns against its indiscriminate use in combination with multiple diuretics, which may limit the drug’s positive effect on metabolism and kidney function, or even turn it to the patient’s disadvantage.
Reference: Hojna S., Malinska H., Huttl M., Markova I., Vanourkova Z., Miklankova D., Hrdlicka J., Papousek F., Neckar J., Behuliak M., Rauchova H., Arora M., Kadlecova M., Zicha J., and Vaneckova I.: Empagliflozin in combination with trandolapril but not with triple therapy improves glucose and lipid metabolism in non-diabetic hypertensive model. Biomed Pharmacother 196, 119045 (2026). IF = 7.5; DOI: 10.1016/j.biopha.2026.119045
