Dagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2) in humans, was originally introduced as a new oral hypoglycemic agent and has been approved for the treatment of type 2 diabetes in China, the United States, and Europe. However, dagliflozin is now increasingly being used in the treatment of patients with heart failure, and why is this?
- How does dagliflozin lower blood sugar?
It turns out that this protein, called SGLT2, plays an important role as a “transporter” in the body’s kidneys. It transports more than 90% of the glucose in the initial urine back to the blood, so that the final urine contains almost no glucose.
Dagliflozin, an inhibitor of SGLT2, selectively acts on SGLT2 so that SGLT2 can no longer do its job, thus blocking the reabsorption of glucose into the bloodstream and allowing it to be excreted from the urine into the body. In this way, the level of glucose in the blood drops. This effect of dagliflozin, which promotes urinary glucose excretion and lowers blood glucose, has made it a star drug for the treatment of type 2 diabetes.
- Does Dagliflozin treat heart failure?
With further research on dagliflozin, it has been found that it promotes the excretion of glucose from the urine while also increasing the excretion of sodium and water, which has many effects beyond “glucose excretion” such as sodium excretion and diuresis, mildly lowering blood pressure, and improving myocardial viability. These effects are ideal for addressing tissue edema, cardiac overload, and abnormal myocardial metabolism in patients with heart failure. The available clinical findings also support the use of dagliflozin in the treatment of heart failure patients, as dagliflozin not only improves quality of life by improving symptoms such as chest tightness, shortness of breath, and edema, but also significantly reduces cardiovascular death and hospitalization for heart failure, and has a protective effect on renal function [1].
Based on the clinical benefit of dagliflozin therapy in patients with heart failure, the US regulatory approval of dagliflozin for the treatment of heart failure with reduced ejection fraction and its availability in non-diabetic patients in May 2020, dagliflozin has become the first SGLT2 inhibitor approved for heart failure treatment. Recently, another SGLT2 inhibitor, engramine, has also shown promising results in studies for the treatment of heart failure with reduced ejection fraction [2].
- What to look for when taking dagliflozin in patients with heart failure.
Although dagliflozin has a high safety profile and a relatively low incidence of adverse reactions, there is still a need to be concerned about possible renal function, hypotension, and hypoglycemia due to the unique nature of heart failure patients.
1. Renal function
Patients with severe renal insufficiency (glomerular filtration rate valuation: eGFR <30 ml/min/1.73 m2) or end-stage renal disease and those requiring dialysis are not currently eligible for dagliflozin. Patients with heart failure are often combined with renal insufficiency, and acute exacerbation of heart failure is often accompanied by deterioration of renal function, which is followed by improvement of renal function after stabilization of heart failure. Therefore, renal function needs to be assessed before starting dagliflozin therapy and monitored dynamically thereafter so that dagliflozin dosage can be adjusted at any time.
2. Hypotension
Dagliflozin diuresis, which mildly lowers blood pressure and reduces blood volume, may cause symptoms of hypotension in patients with heart failure. When patients with heart failure, especially the elderly, those with significantly reduced ejection fraction, and those on high-dose diuretics take dagliflozin, they need to be closely monitored for symptoms such as dizziness, panic, and weakness, and have their blood pressure measured regularly. If the blood pressure is low, the doctor should be informed promptly.
3. Hypoglycemia
The risk of hypoglycemia with dagliflozin is small, and hypoglycemia occurs mainly in association with other basal hypoglycemic therapy and is not a concern in normoglycemic individuals. The occurrence of hypoglycemia is increased when dagliflozin is combined with sulfonylureas or insulin, so it may be necessary to reduce the dose of sulfonylureas or insulin to avoid hypoglycemia when combined in patients with diabetes.
4. Genitourinary tract infections
Dagliflozin inhibits renal reabsorption of glucose, which increases the concentration of glucose in the urine and creates a “suitable” environment for bacterial growth, thus triggering urinary tract infections. Patients with low eGFR and a history of previous genitourinary tract infections are more likely to develop genitourinary tract infections, a problem that requires attention. During the use of Dagliflozin, you need to pay attention to personal hygiene of the vulva, drink an appropriate amount of water, and keep urine flowing smoothly to reduce the occurrence of infections. If an infection occurs during use, you can suspend use of the drug and receive anti-infection treatment first.
5. Ketoacidosis (DKA)
The incidence of DKA from taking dagliflozin is actually very low and is mainly in patients with diabetes. The incidence of DKA is actually low and mainly in patients with diabetes mellitus. To avoid DKA, diabetic patients should not consume excessive amounts of alcohol while using dagliflozin and should not reduce or stop insulin too quickly. It may be necessary to discontinue dagliflozin in the event of stressful situations such as the need for major surgery or severe infection.
Dr. Zhang Qian of Beijing Anzhen Hospital, Capital Medical University, contributed to this article