The FDA issued a warning message on August 29, 2018:
Cases of rare, severe genital and genital area infections of sodium-glucose cotransporter 2 (SGLT2) inhibitors have been received.
This rare and serious infection is called perineal necrotizing fasciitis, also known as Funeral gangrene.
The FDA believes that new warnings about this risk need to be added to all SGLT2 inhibitor prescription information and patient medication guidelines.
1. Patients should pay attention to:
If the genitals or areas from the genitals to the rectum are tender, red, swollen, and have a fever of more than 38 ° C or a general discomfort, see a doctor immediately.
These symptoms worsen quickly and you must see your doctor immediately.
2. Medical staff should pay attention to:
If the patient has the above symptoms, consider whether it is Funeral gangrene. If suspected, broad-spectrum antibiotics and surgical debridement should be used immediately.
Stop SGLT2 inhibitors, closely monitor blood glucose levels, and provide appropriate replacement therapy for glycemic control.
The currently approved SGLT2 inhibitors for clinical use are dapagliflozin, englitavir, and calpagliflozin.
The hypoglycemic mechanism of SGLT2 inhibitors:
The SGLT2 inhibitor promotes urinary glucose excretion by inhibiting sodium-glucose cotransporter 2 (SGLT2) in the kidney, thereby reducing glucose levels in the blood circulation.
SGLT2 inhibitors reduce HbA1c by approximately 0.5% to 1.0%; weight loss by 1.5 to 3.5 kg, and reduction of systolic blood pressure by 3 to 5 mmHg.
Among them, Engleet is also approved by the FDA to reduce the risk of heart disease and stroke in adults with type 2 diabetes and heart disease.
The hypoglycemic effect of SGLT2 is comparable to metformin. SGLT2 inhibitors do not increase the risk of hypoglycemia when used alone, and may increase the risk of hypoglycemia when combined with insulin or sulfonylureas.
Adverse reactions of SGLT2 inhibitors:
Common adverse effects of SGLT2 inhibitors are genitourinary tract infections, and rare side effects include ketoacidosis (mainly in patients with type 1 diabetes).
Possible adverse reactions include acute kidney injury (rare), fracture risk (rare), and toe amputation (see Kagliel).
1. Low blood pressure risk
SGLT2 inhibitors cause osmotic diuresis, which causes a decrease in blood volume and dose-dependent hypotension: orthostatic dizziness, orthostatic hypotension, syncope, and dehydration.
After starting treatment, patients may experience symptomatic hypotension, especially in patients with renal impairment, elderly patients, patients receiving diuretics, ACEI, ARB antihypertensive drugs, or patients with lower systolic blood pressure.
2. Incidence of genital fungal infections
SGLT2 inhibitors, mainly by increasing the excretion of urine glucose, can cause genital fungal infections such as vaginal fungal infections, vaginal infections, genital fungal infections, vulvovaginal candidiasis and vulvitis.
Patients with a history of genital fungal infections are more susceptible to genital fungal infections during the study period.
Genital fungal infections can also occur in male patients, such as candidal balanitis, foreskin balanitis, etc., but the incidence is generally lower than in female patients.
3. Risk of lower extremity amputation – Cagliflozin:
In two large, randomized, placebo-controlled trials (CANVAS and CANVAS-R) for patients with type 2 diabetes who had previous history of cardiovascular disease (CVD) or CVD risk factors, lower extremity amputation was observed after taking calpagliflozin The risk has increased by about double.
The risk of lower extremity amputation was observed in both 100 mg and 300 mg once daily dosing regimens.
In the CANVAS trial, the number of amputations per year for patients receiving and receiving placebo was 5.9 and 2.8 per 1000 patients, respectively.
In the CANVAS-R trial, the number of amputations per year for patients receiving this product and those receiving placebo was 7.5 and 4.2 per 1000 patients, respectively.