From the Guidelines
SGLT2 inhibitors can cause several adverse effects, including genital mycotic infections, urinary tract infections, volume depletion, diabetic ketoacidosis, and increased risk of lower limb amputations and bone fractures, particularly with canagliflozin, and patients should be closely monitored for these effects, as recommended by the most recent guidelines 1.
Adverse Effects of SGLT2 Inhibitors
The most common side effects of SGLT2 inhibitors are:
- Genital mycotic infections, particularly in women, due to increased glucose in the urine creating an environment favorable for fungal growth
- Urinary tract infections, which may occur for similar reasons
- Volume depletion, which can lead to dizziness, lightheadedness, and orthostatic hypotension, especially in elderly patients or those taking diuretics
Serious but Rare Complications
A serious but rare complication is diabetic ketoacidosis, which can occur even with near-normal blood glucose levels (euglycemic DKA) 1. Patients should be educated to temporarily discontinue these medications during acute illness, surgery, or prolonged fasting.
Risk Mitigation Strategies
Risk mitigation strategies for SGLT2 inhibitor side effects should include:
- Hygienic counseling to avoid genital mycotic and urinary tract infections
- Sick day rules and insulin guidance for reducing risk of “normoglycemic” ketoacidosis
- Reduction of diuretics for patients at risk for hypovolemia or hypotension, as recommended by the most recent guidelines 1
Monitoring and Management
Patients starting an SGLT2 inhibitor should be informed about the higher risk of genital mycotic infections and advised to seek immediate care if they develop symptoms potentially associated with diabetic ketoacidosis 1. Monitoring of renal function in the first several weeks of therapy is reasonable, particularly in patients with impaired renal function at baseline.
Benefits of SGLT2 Inhibitors
Some SGLT2 inhibitor side effects are beneficial, such as reducing risks of hyperkalemia, without causing hypokalemia, and mitigating fluid retention, which can facilitate initiation and persistent use of other guideline-directed medical therapies 1.
From the FDA Drug Label
In some but not all cases, factors predisposing to ketoacidosis such as insulin dose reduction, acute febrile illness, reduced caloric intake due to illness or surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients receiving SGLT2 inhibitors, including JARDIANCE; some reports involved patients younger than 65 years of age There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors, including JARDIANCE. The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin JARDIANCE increases the risk for genital mycotic infections There have been postmarketing reports of serious hypersensitivity reactions, (e.g., angioedema) in patients treated with JARDIANCE. Increases in LDL-C can occur with JARDIANCE
The adverse effects of SGLT2 inhibitors, such as empagliflozin, include:
- Ketoacidosis: increased risk due to factors like insulin dose reduction, acute illness, and pancreatic disorders
- Acute kidney injury: increased risk due to factors like hypovolemia, chronic renal insufficiency, and concomitant medications
- Urosepsis and pyelonephritis: increased risk of serious urinary tract infections
- Hypoglycemia: increased risk when used with insulin secretagogues or insulin
- Genital mycotic infections: increased risk, especially in patients with a history of chronic or recurrent infections
- Hypersensitivity reactions: risk of serious reactions, such as angioedema
- Increased LDL-C: potential increase in low-density lipoprotein cholesterol levels 2
From the Research
Adverse Effects of SGLT2 Inhibitors
- SGLT2 inhibitors are associated with an increased risk of genitourinary infections, including urinary tract infections (UTIs) and genital infections (GIs) 3, 4, 5, 6, 7.
- The incidence of UTIs and GUIs is higher in patients treated with SGLT2 inhibitors compared to those treated with placebo or other antidiabetic agents 3, 7.
- Genital mycotic infections are a common adverse effect of SGLT2 inhibitors, with a higher risk observed in patients treated with these agents compared to other antidiabetic agents 4, 6.
- Euglycemic ketoacidosis is a rare but serious adverse effect of SGLT2 inhibitors, highlighting the need for careful monitoring and patient management strategies 4, 6.
- SGLT2 inhibitors may also be associated with a low risk of hypotension and hypoglycemia, although these effects are less common compared to genitourinary infections 4, 6.
Risk Factors and Patient Management
- Patients with type 2 diabetes mellitus (T2DM) are more prone to experiencing UTIs and recurrent UTIs compared to individuals without T2DM, highlighting the need for careful risk assessment and monitoring in clinical decision-making 5.
- The management of diabetes and lifestyle modifications with a patient-centric approach are essential for preventing critical long-term complications, including genitourinary manifestations of diabetes 5.
- Healthcare providers should be aware of the potential risks associated with SGLT2 inhibitors and take steps to minimize these risks, including careful patient selection, monitoring, and education 3, 4, 6, 7.