Grandpa Wang's son said to the doctor dissatisfied: Did you prescribe the wrong medicine to my father, I checked on the Internet, and dapagliflozin is obviously for the treatment of diabetes, and my father does not have diabetes!
Let's take a look at Grandpa Wang's case.
Grandpa Wang, 83, went to a nearby hospital accompanied by his son because he felt poor appetite, fatigue, chest tightness and shortness of breath for a long time. He described to the doctor: I felt chest tightness, breathlessness, coughing, and my blood pressure was a little high after a little movement.
Grandpa Wang's son added on the side: My dad always forgot to take blood pressure medicine, I often called him to remind him, and finally always forgot to take it.
The doctor first examined Grandpa Wang's basic vital signs: body temperature of 37°C, pulse of 115 beats/min, breathing of 20 breaths/min, and blood pressure of 168/89mmHg. Then the doctor did a physical examination of Grandpa Wang, and the chest percussion found that the heart was enlarged, indicating that the heart was enlarged, and the auscultation found a murmur in the apical area, and the doctor judged that it might be mitral valve (relative) regurgitation. Because Grandpa Wang had chest tightness, in order to rule out an acute myocardial infarction, the doctor did an electrocardiogram for him in the consultation room, and the results showed that the QRS complex voltage in lead V5 was increased and the time limit was prolonged, indicating left ventricular hypertrophy and no signs of myocardial infarction.
At this time, the doctor had already come to a preliminary conclusion: Grandpa Wang was very likely to have heart failure.
Because Grandpa Wang did not take antihypertensive drugs regularly as prescribed by the doctor, his blood pressure was not well controlled, and the prolonged increase in blood pressure led to difficulty in ejection from the left ventricle of the heart. In order to pump blood from the left ventricle throughout the body, the body initiates a compensatory mechanism that makes the left ventricle hypertrophied, resulting in the enlargement of the ventricular cavity, which can lead to mitral regurgitation, which can easily lead to left heart failure in the long run. In order to refine the diagnosis and guide treatment, the doctor prescribes a number of auxiliary tests.
The results of the examination came out quickly: white blood cells 7.1×109/L, hemoglobin 116.00g· L-1↓, platelets 79×109/L↓, C-reactive protein 27.20mg· L-1↑, normal blood glucose and lipids.
Three items of myocardial infarction were normal, NT-proBNP: 14843.00 pg·mL-1↑, and elevated NT-proBNP was indicative of heart failure, which was also confirmed by cardiac ultrasound: decreased ejection fraction, increased left ventricular end-diastolic diameter, marked left ventricular enlargement, and moderate mitral regurgitation.
Therefore, the doctor gave a diagnosis: hypertension class II., chronic heart failure, cardiac function class III (NYHA classification), mitral regurgitation. Grandpa Wang wanted to be treated with medication, so the doctor prescribed spironolactone, dapagliflozin, and benazepril. And then there's the conversation that happened at the beginning, let's take a look at how the doctor explained it to them.
1. Dapagliflozin can only be used for diabetes?
Grandpa Wang's son's doubts are understandable. Because dapagliflozin was originally developed to treat diabetes, researchers later discovered that drugs like dapagliflozin can also treat heart failure, high blood pressure and kidney failure.
Such a wide range of effects are mainly related to the unique mechanism of action of the drug, such as dapagliflozin and other drugs containing the word Liflozin are SGLT-2 inhibitors, which is a transporter located on the proximal convoluted tubule of the renal tubule of the kidney.
Its function is mainly to reabsorb glucose back into the body, and it is difficult for non-professionals to understand the meaning of reabsorption here, so let's take a closer look.
Ordinary people know that the kidneys have the function of filtration, so it is not difficult to understand that blood flows into the kidneys every moment to remove metabolic waste products through screening.
About 180 liters of plasma flow through the kidneys every day, but we don't have 180 liters of urine per day, mainly because most of the components filtered by the kidneys are reabsorbed back into the body except for metabolic wastes.
At this point, it is easy to understand that glucose is the body's energy supply, so it must be reabsorbed and reused. SGLT-2 is responsible for the reabsorption of glucose, and dapagliflozin can inhibit it, so it can prevent glucose reabsorption.
But it still can't explain that it has anti-heart failure, high blood pressure and kidney failure, so let's take a look at them one by one.
2. How does dapagliflozin act on heart failure?
A 2023 study involving 14,032 participants found that dapagliflozin reduced hospitalizations in patients with heart failure (RR = 0.76, 95% CI: 0.70-0.84, P>0.001), with no statistical heterogeneity (I2 = 0%).
In addition, a growing number of studies support the use of SGLT-2 inhibitors in the treatment of heart failure, and the addition of SGLT-2 inhibitors such as dapagliflozin to standard treatment can further reduce the risk of cardiovascular death and hospitalization for heart failure.
As a result, many countries, including China, have included dapagliflozin in their guidelines as a new treatment for heart failure.
The principle of dapagliflozin in the treatment of heart failure is mainly to reduce the workload of the heart, improve cardiac energy metabolism and ventricular remodeling.
It can be inferred that heart failure is due to the heavy load on the heart, lack of energy, and ventricular remodeling (ventricular remodeling can be understood as the deformation of the heart). For example, if you don't take antihypertensive drugs on time, your blood pressure will be too high, which will increase the resistance of the heart to eject blood, a phenomenon called increased afterload of the heart.
The increase in afterload causes the heart to remain in the ventricles with the amount of blood that should have been ejaculated every time it contracts, and the extra blood will cause a certain amount of pressure on the heart, which is called preload, so in general, the load on the heart is aggravated.
In addition, because the ejection volume of the heart decreases, the blood volume of the tissues of the whole body decreases, and the body will compensate for the ischemia caused by insufficient contraction by stimulating the sympathetic nerve to increase the heart rate, and at the same time, it will cause the myocardial oxygen consumption to increase and lack energy.
The body can also hypertrophy the left ventricle to improve myocardial contractility, but over time these compensatory mechanisms fail, and the heart's ability to eject blood is further reduced.
Due to insufficient stroke volume, the whole body is in a state of ischemia, and the body will judge that it is in a state of volume depletion at this time, and the RAAS system will be activated, which is manifested by vasoconstriction and water and sodium retention, which increases the pre- and post-load of the heart, and further aggravates the cardiac load.
SGLT-2 inhibitors can reduce cardiac workload by inhibiting not only glucose reabsorption but also sodium reabsorption, and water reabsorption due to the higher osmolarity of glucose and sodium.
Therefore, it can reduce the reabsorption of water, so that the urine output increases, the blood pressure decreases, and it can also reduce the workload of the heart by preventing the hardening of the arteries and dilating the blood vessels.
In contrast to traditional diuretics, which passively reduce water reabsorption by directly reducing sodium reabsorption, SGLT-2 inhibitors may have a stronger ability to clear free water.
SGLT-2 inhibitors can promote the production of ketone bodies from fatty acids in fat cells in the liver, increasing the rate of cardiac ketone oxidation, thereby improving the energy supply of the failing heart. In addition, it exerts cardioprotective effects by inhibiting inflammation-related molecular processes, alleviating vascular oxidative stress, slowing down the process of myocardial fibrosis, and normalizing ejection fraction, and it can also exert a protective effect on the kidneys.
3. How does dapagliflozin protect the kidneys?
SGLT-2 inhibitors such as dapagliflozin reduce the risk of deteriorating kidney function, end-stage renal disease, or death from kidney disease by 45%, with and without atherosclerotic cardiovascular disease and heart failure.
Therefore, in the latest expert consensus on the treatment of chronic kidney disease in nephrology, dapagliflozin, its anti-renal failure effect has been included, and the main discussion here is anti-chronic renal failure, because it is more common. Chronic renal failure is often secondary to various chronic diseases, such as hypertension and diabetes. Its main features are proteinuria, anemia, and decreased glomerular filtration rate (GFR).
High blood pressure causes damage to the small arteries in the kidneys, and the constriction and hardening of these blood vessels can cause blood flow to slow down, causing kidney ischemia.
After ischemia, some nephrons are damaged, and due to the compensatory mechanism, the other part of the nephron will work in place of the damaged nephron, so that these nephrons have a hypermetabolic state of high stress, hyperperfusion, and high filtration.
This injures endothelial cells, increases platelet aggregation, and causes inflammatory cell infiltration and mesangial cell apoptosis.
The main reason why SGLT-2 inhibitors can treat chronic renal failure is that they reduce glomerular filtration rate and reduce stress, perfusion, and filtration.
One of the specific mechanisms is that SGLT-2 inhibitors can inhibit the activation of the RAS system in the kidney to exert a renal protective effect. The second is that the SGLT-2 inhibitor hinders Na+ reabsorption in the proximal convoluted tubule, resulting in an increase in Na+ flowing downstream to the dense spot of the distal convoluted tubule. When dense plaques feel an increase in Na+, they initiate tubular feedback, which constricts the glomerular entry and diastolic arteries, and thus decreases the glomerular filtration rate.
One question worth exploring here is whether reducing glomerular filtration rate worsens renal impairment?
Dapagliflozin has been shown to reversibly alter renal hemodynamics. Glomerular filtration rate decreases during dapagliflozin administration, but renal function does not deteriorate, or glomerular filtration rate returns to baseline after discontinuation of the drug.
The greater damage lies in endothelial cell damage, which can lead to the production of proteinuria, and long-term proteinuria leads to hypoproteinemia, weakened immune system, anemia, edema, and other problems.
A prospective, multicenter clinical study in Japan showed that the urine albumin to creatinine ratio decreased by 0.37±0.73 in 86 participating patients at 24 weeks (P<0.001).
In addition, the changes from baseline in morning and night home blood pressure measurements were as follows: systolic/diastolic blood pressure decreased by 8.32 ± 11.42 mmHg in the morning (P<0.001) and decreased by 9.57 ± 12.08 mmHg at night (P<0.001).
Therefore, dapagliflozin can reduce urine protein and systolic blood pressure, so it can improve the problem of hypoproteinemia and hypertension in patients. In addition to improving the problem of proteinuria, SGLT-2 inhibitors such as dapagliflozin can also have anti-inflammatory, antioxidative stress, anti-fibrosis, reduce blood sugar, body weight, blood pressure and other effects, so that the patient's systemic metabolic status can be improved, and finally the development of chronic renal failure can be delayed.
Although dapagliflozin has so many benefits, there are still some side effects like infections of the urinary and reproductive systems, manifestations of volume depletion such as dehydration, possible hypoglycemia when used in combination with insulin medications, etc.
Also, note that it is generally not recommended to use with quinolones and some β receptor antagonists.
Therefore, it is not recommended to use it on your own and should be used under the guidance of a doctor. But you still don't need to worry too much about its safety, as studies have shown that dapagliflozin is safer.
brief summary
Dapagliflozin, an SGLT-2 inhibitor, is used not only to treat diabetes, but also heart failure, high blood pressure and kidney failure. It can reduce the workload of the heart, improve cardiac energy metabolism and ventricular remodeling, thereby reducing the risk of cardiovascular death and hospitalization for heart failure, reduce the reabsorption of water and sodium, help lower blood pressure, and finally reduce the glomerular filtration rate, reduce the pressure on the kidneys in patients with chronic renal failure, thereby delaying the development of chronic renal failure.
While dapagliflozin has a variety of therapeutic benefits, there are also some side effects, such as urinary tract infections and dehydration, so it should be used under the guidance of a doctor.
Bibliography:
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