How safe and effective is dapagflozin in patients with type 2 diabetes based on blood pressure levels?

This study analyzed the safety and effectiveness of dapagliflozin (Farxiga) in patients with type 2 diabetes (T2D) across different ranges of baseline systolic blood pressure (SBP; blood pressure when the heart beats). The data suggested that dapagliflozin reduced the risk of hospitalization for heart failure (HHF) and kidney-related outcomes and was safe for use across different levels of SBP without causing an increase in short-term (acute) kidney injury, dehydration, or amputations in patients.

Many patients with T2D often have hypertension (high blood pressure; BP). These patients commonly have high risks of cardiovascular disease (CVD). Consistently high SPB (upper value of BP measurement) increases the risk of heart failure (HF) and acute kidney injury. Dapagliflozin is a drug that lowers blood glucose (sugar) levels. It reduces glucose and sodium resorption in the kidneys while promoting the elimination of glucose in urine. It has also been shown to reduce BP.

Dapagliflozin belongs to a class of drugs called sodium-glucose co-transporter 2 inhibitors (SGLT2i). On average, large decreases in BP do not occur after the administration of SGLT2i. However, there are safety concerns about using SGLT2i in patients with low to normal SPB. There is a need to investigate the safety and benefits of dapagliflozin use in patients with T2D across differing baseline levels of SBP.

This study involved a total of 17,160 patients with T2D. Patients were randomly assigned to receive either 10 mg of once-daily dapagliflozin or a placebo. Patients were then assigned to groups according to their average baseline SBP. The groups were defined based on patients' average SBP: normal group (SBP<120mmHg), elevated (SBP=120-129mmHg), stage I (SBP=130-139mmHg), stage II (SBP=140-159mmHg), and severe hypertension (SBP>=160mmHg). Patients were followed for an average of 48 months.

Overall, at 48 months, dapagliflozin reduced SBP by 2.4 mmHg compared to placebo. This reduction was seen across all groups and regardless of the BP-lowering drugs used. 

Dapagliflozin significantly reduced the risk of HHF and kidney outcomes across all groups. Particular benefits with dapagliflozin were seen in the normal and elevated groups regarding HHF and kidney injury outcomes. Overall, no differences were observed in dehydration symptoms, amputation, and acute kidney injury across groups.

The study indicated that the administration of dapagliflozin may be beneficial to patients with T2D at high risk of heart disease regardless of their baseline blood pressure.

The study was not specifically designed to determine the protective effects of dapagliflozin based on blood pressure reduction. This study received funding from AstraZeneca, the manufacturer of dapagliflozin.