The difference between empagliflozin, dapagliflozin, canagliflozin and ertugliflozin. 😵😵😵

Nowadays, the pros and cons of hypoglycemic drugs are no longer based on the hypoglycemic value as an evaluation criterion, but whether they have heart and kidney protection while reducing blood glucose as the evaluation criterion. SGLT2 inhibitors are a new type of oral hypoglycemic drugs that have received great attention in recent years. In addition to the treatment of type 2 diabetes, it is also used for the treatment of chronic heart failure and chronic kidney disease. Empagliflozin, dapagliflozin, canagliflozin and ertugliflozin are very commonly used SGLT2 inhibitors. What is the difference between them?

1. Hypoglycemic mechanism.

The full name of SGLT2 inhibitors is sodium-glucose cotransporter 2 inhibitor. Normally, the glucose filtered through the glomerulus per day is about 180g/d, but all glucose will be reabsorbed by the sodium-glucose cotransporter (SGLT1, SGLT2) on the renal tubules. SGLT2 inhibitors reduce the reabsorption of glucose and sodium by the kidneys by inhibiting SGLT2. It can excrete 70~80g/d glucose from the urine, thereby exerting a hypoglycemic effect, and has a certain hypotensive effect. 

2. Other effects.

SGLT2 inhibitors can reduce glycosylated hemoglobin (HbA1c) 0.5-1.2%, weight 0.6-3.0kg, systolic blood pressure 3-5mmHg, and blood uric acid about 50μmol/L. They are all good for heart failure. SGLT2 inhibitors have shown cardiovascular and renal benefits in a series of large cardiovascular and renal outcomes studies. Among them, only empagliflozin and canagliflozin are beneficial to atherosclerotic vascular disease. Empagliflozin, canagliflozin and dapagliflozin are beneficial for delaying chronic kidney disease.

3. Clinical application.

The 2022 edition of "ADA Diabetes Medical Diagnosis and Treatment Standards" recommends:

For patients with atherosclerotic vascular disease, heart failure and/or diabetic kidney disease, it is recommended to use GLP-1 receptor agonists or SGLT-2 inhibitors as the initial treatment. According to the patient's blood sugar status, metformin is combined or not combined.

ASCVD/high-risk factors: It is recommended to use GLP-1 receptor agonist or SGLT2 inhibitor. Choose GLP-1 receptor agonists that have proven cardiovascular benefits: dulaglutide, liraglutide and semaglutide. Choose SGLT2 inhibitors that have proven cardiovascular benefits: empagliflozin and canagliflozin.

Heart failure: It is recommended to choose SGLT2 inhibitors that have been proven to be beneficial for heart failure: empagliflozin, canagliflozin, dapagliflozin and ertugliflozin.

Chronic kidney disease: 

Patients with chronic kidney disease and proteinuria should first choose SGLT2 inhibitors that can delay the progression of chronic kidney disease: canagliflozin, empagliflozin and dapagliflozin. If SGLT2 inhibitors are contraindicated/intolerant, choose GLP1 receptor agonists with cardiovascular benefits: dulaglutide, liraglutide and semaglutide. 

Patients with chronic kidney disease who do not have proteinuria should choose GLP-1 receptor agonists or SGLT2 inhibitors that have cardiovascular benefits.

4. Dosage.

SGLT2 inhibitor has diuretic effect. To avoid excessive nocturia, it is recommended to take it in the morning. They are not affected by meals.

Empagliflozin: It has a peak time of 1.5 hours and a half-life of 12.4 hours. Its recommended dosage is 10 mg once a day. The maximum dose is 25 mg once a day.

Dapagliflozin: It has a peak time of 2 hours and a half-life of 12.9 hours. Its recommended dosage is 5 mg once a day. The maximum dose is 10 mg once a day.

Canagliflozin: It has a peak time of 1-2 hours and a half-life of 10.6-13.1 hours. Its recommended dosage is 100 mg once a day. The maximum dose is 300 mg once a day.

Ertugliflozin: It has a peak time of 1 hours and a half-life of 16.6 hours. Its recommended dosage is 5 mg once a day.

5. Adverse effects.

Urinary and reproductive tract infections: SGLT2 inhibitors play a hypoglycemic effect mainly by promoting urinary glucose excretion. Due to the increased concentration of glucose in urine, SGLT2 inhibitors can significantly increase the risk of urinary tract infections and genital fungal infections. During the medication, you should increase the amount of drinking water and keep the vulva clean. If urinary tract infections and reproductive tract infections occur, symptomatic treatments such as antibacterial drugs (including antifungal drugs) are required.

Hypovolemia: SGLT2 inhibitors have an osmotic diuretic effect, which can lead to a decrease in blood volume. Elderly patients or those taking loop diuretics (such as furosemide) are at increased risk of hypovolemia. The main manifestations of hypovolemia are dehydration, orthostatic hypotension or hypotension.

Fracture risk: Patients with type 2 diabetes are more likely to fracture than the general population. The main fracture sites are the hip, foot and proximal femur. SGLT inhibitors can inhibit the reabsorption of sodium in the renal tubules and increase the reabsorption of phosphorus. This leads to increased blood phosphorus levels, stimulates parathyroid hormone secretion, and increases bone resorption. Canagliflozin can increase the risk of fractures.