Empagliflozin

Common name: empagliflozin

Product name: Jardiance

All names: Empagliflozin, Ou Tangjing, Empagliflozin, Jardiance

Indications:

Suitable for the treatment of type 2 diabetes.

Used in combination with metformin hydrochloride

When metformin hydrochloride alone cannot control blood sugar, empagliflozin can be used in combination with metformin hydrochloride to control blood sugar in patients with type 2 diabetes on the basis of diet and exercise.

Used in combination with metformin hydrochloride and sulfonylureas

When the combined use of metformin hydrochloride and sulfonylureas still fails to control blood sugar, empagliflozin can be used in combination with metformin hydrochloride and sulfonylureas to control blood sugar in patients with type 2 diabetes on the basis of diet and exercise.

Usage and dosage:

The recommended dose is 10 mg once a day in the morning, on an empty stomach or after food. In patients who tolerate empagliflozin, the dose may be increased to 25 mg.

Patients with kidney damage

It is recommended to assess renal function before starting empagliflozin and periodically thereafter. Patients with eGFR (glomerular filtration rate) less than 45mL/min/1.73㎡ should not use empagliflozin. Patients with eGFR greater than or equal to 45mL/min/1.73㎡ do not require dose adjustment. If eGFR continues to be lower than 45mL/min/1.73㎡, empagliflozin should be discontinued.

Patients with liver damage

No dose adjustment is required in patients with hepatic impairment. Empagliflozin exposure is increased in patients with severe hepatic impairment. There is limited experience in treating patients with severe hepatic impairment, and therefore, its use is not recommended for this population.

Adverse reactions:

>10%

Urinogenital system: urinary tract infection (9%; women: 18%; men: 4%)

1%—10%

Endocrinology and metabolism: dyslipidemia (4%), increased thirst (2%)

Gastrointestinal: Nausea (2%)

Urinogenital system: increased urine output (3%)

Hematology and Oncology: Increased hematocrit (3%-4%)

Infection: urogenital fungal infection (2%-6%)

Frequency undefined: Endocrinology and Metabolism: Elevated LDL cholesterol

<1%

Postmarketing or case reports: Acute renal failure, angioedema, decreased estimated GFR (eGFR) (glomerular filtration rate), allergic reactions, hypovolemia, increased serum creatinine, ketoacidosis, necrotizing fasciitis (perineal), phimosis, pyelonephritis, rash, urinary tract infection with sepsis, urticaria

Taboo:

History of severe allergy to empagliflozin or any of its ingredients

Severe renal impairment, end-stage renal disease, or dialysis

Notes:

Fractures: An increased incidence of fractures has been observed with other SGLT-2 inhibitors in some clinical trials. However, a meta-analysis of empagliflozin trial data did not show an increased risk of fractures.

Reproductive tract fungal infection: May increase the risk of genital tract fungal infection (such as vulvovaginal fungal infection, vulvovaginal candidiasis, vulvovaginitis, candidal balanitis, balanitis). Patients with a history of these infections or uncircumcised men are at greater risk.

Hypersensitivity Reaction: Hypersensitivity reactions (e.g., angioedema, cutaneous urticaria) have been observed; if a hypersensitivity reaction occurs, discontinue immediately and treat as directed. It is contraindicated in those with severe allergies to empagliflozin.

Hypotension: Symptomatic hypotension can be caused by reduced intravascular volume, especially renal damage (i.e. eGFR<60 mL/min/1.73㎡), the elderly, patients taking other antihypertensive drugs (such as diuretics, ACE inhibitors, angiotensin receptor blockers [ARBs]) or patients with low systolic blood pressure. Assess the volume status of patients at risk for hypotension before initiating therapy and correct if depleted; monitor for signs and symptoms of hypotension after initiating therapy.

Ketoacidosis: Cases of ketoacidosis (some fatal) have occurred in patients with type 1 and type 2 diabetes treated with sodium-glucose cotransporter 2 (SGLT-2) inhibitors; in some cases, patients experienced normal or mildly elevated blood glucose (<250 mg/dL). Before initiating treatment, consider risk factors that may lead to ketoacidosis (such as pancreatic insulin deficiency, reduction or discontinuation of insulin dose, caloric restriction, alcohol abuse, heavy exercise, myocardial infarction, stroke, serious infection, surgery, any other extreme stressful event). The American Association of Clinical Endocrinologists and the American College of Endocrinology recommend considering not using SGLT-2 inhibitors for at least 24 hours before an event that could lead to diabetic ketoacidosis occurs, while others recommend not using SGLT-2 inhibitors for 3 to 5 days. Patients who develop nausea, vomiting, abdominal pain, general malaise, or shortness of breath should be evaluated immediately for ketoacidosis; if ketoacidosis is suspected, treatment should be discontinued and treated immediately.

Lipid abnormalities: can cause an increase in low-density lipoprotein cholesterol (LDL-C); monitor LDL-C and treat as needed.

Kidney Effects: Acute kidney injury has been reported. Before initiating, consider risk factors for acute kidney injury (e.g., hypovolemia, chronic renal insufficiency, heart failure, use of concomitant medications (e.g., diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or nonsteroidal anti-inflammatory drugs)). Temporarily discontinue use if oral intake or fluid loss is reduced; discontinue use if acute kidney injury occurs. Other abnormalities of renal function (decreased eGFR, increased serum creatinine) and adverse reactions related to renal function may occur. In the EMPA-REG Outcome Study, administration of empagliflozin resulted in an early decrease in eGFR (glomerular filtration rate) that stabilized after approximately 4 weeks. Assess renal function before starting treatment and periodically during treatment.

Absorption changes: Absorption may be altered due to anatomic and transport changes caused by gastric bypass and sleeve gastrectomy.

Dehydration: Assess, correct, and maintain postoperative fluid requirements and volume status before initiating treatment and monitor patients closely during treatment; volume depletion and related adverse events (e.g., hypotension, orthostatic hypotension, syncope). Fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric banding.

Diabetic ketoacidosis: Stop treatment 3-5 days before surgery. Assess volume status, caloric intake, and need for diabetic treatment postoperatively, and discontinue antidiabetic medications if type 2 diabetes remits. Ketoacidosis has been reported in patients with type 1 and type 2 diabetes taking SGLT-2 inhibitors. In some cases, blood glucose is normal or mildly elevated (<250 mg/dL). Risk factors include significant decreases in insulin, caloric restriction, surgical stress, and infection.

Kidney function impairment: In the event of kidney function damage, blood glucose efficacy may be reduced. Assess renal function before starting treatment and periodically during treatment. It is prohibited for patients with severe renal impairment (eGFR<30ml/min/1.73㎡), ESRD (end-stage renal disease) and dialysis. According to the manufacturer: Empagliflozin should not be used in patients with eGFR <45ml/min/1.73m2 and should be discontinued when eGFR continues to be <45ml/min/1.73m2. In the EMPA-REG Outcomes trial, empagliflozin reduced the odds of incident or worsening nephropathy (secondary endpoint) and high cardiovascular risk in patients with diabetes with eGFR ≥30ml/min/1.73m2 who received standard of care. Post hoc analyzes suggested that renal benefit may persist in patients with baseline renal impairment (eGFR 30 to <60 ml/min/1.73 m2). An additional post hoc analysis showed that cardiovascular mortality was consistent among subgroups with eGFR 30 to <45, 45 to <60, and ≥60 ml/min/1.73 m2. However, further trials may be necessary to determine whether outcomes in patients with renal impairment can be improved.

Drug-drug interactions: Significant interactions are possible that may require dose or frequency adjustment, additional monitoring, and/or the selection of alternative therapies.

Elderly: Elderly patients may be at increased risk for intravascular volume failure, renal impairment, and urinary tract infection.

Pregnancy: Based on animal data showing renal adverse reactions, use of this product in the second and third trimesters of pregnancy is not recommended. Data on the use of this product in pregnant women are limited and insufficient to determine the drug-related risk of major birth defects and miscarriage. Poorly controlled gestational diabetes can pose risks to both mother and fetus.

Disease-related maternal and/or embryo/fetal risks: Poorly controlled gestational diabetes increases the maternal risk of diabetic ketoacidosis, preeclampsia, spontaneous abortion, prematurity, stillbirth, and delivery complications. Poorly controlled diabetes increases the risk of major birth defects, stillbirth, and macrosomia-related morbidities in the fetus.

Pediatric use: The safety and effectiveness of this product in pediatric patients younger than 18 years of age have not been established.

Lactation period: Empagliflozin can be secreted in the milk of nursing rats. Because human renal maturation is completed in utero and during the first 2 years of life (when lactational exposure may occur), there may be risks to human renal development. Because of the potential for serious adverse reactions in nursing infants receiving this product, women should be informed that use of this product during breastfeeding is not recommended.

Scope of application: Not suitable for patients with diabetic ketoacidosis or type 1 diabetes.

Store:

Store at 25°C (77°F); drift allowed between 15°C to 30°C (59°F to 86°F).

Mechanism of action:

Sodium glucose co-transporter 2 (SGLT-2) is the main transporter that reabsorbs glucose from the glomerular filtrate into the blood circulation. Empagliflozin is an SGLT2 inhibitor that reduces renal glucose reabsorption, lowers the renal glucose threshold, and promotes glucose excretion from the urine.

Safety and efficacy:

Empagliflozin has good safety and can reduce the risk of cardiovascular events and the progression of kidney disease in patients with diabetes. It is the world's first type 2 diabetes drug proven to reduce the risk of cardiovascular death by a large cardiovascular outcome study (EMPA-REG OUTCOME®).

A large amount of medical evidence-based evidence confirms that empagliflozin can quickly excrete sugar, effectively lower blood sugar, stabilize sugar control, improve β-cell function, and can also reduce weight. It has additional benefits such as fat reduction and liver fat reduction. It has good safety and is currently the preferred anti-diabetic drug recommended by authoritative guidelines at home and abroad. It is an ideal choice for patients with T2DM (type 2 diabetes). It is reported that Empagliflozin (Ou Tangjing®) recently won the "Best Drug" award at the Prix Galien International 2018. Globally, the award is considered the equivalent of the Nobel Prize in pharmaceutical research and innovation.