What are the side effects of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors?

From the Guidelines

SGLT2 inhibitors can cause several side effects, including genital mycotic infections, urinary tract infections, volume depletion, diabetic ketoacidosis, and increased risk of lower limb amputations and bone fractures, as reported in the most recent study 1.

Common Side Effects

• Genital mycotic infections (yeast infections), particularly in women, due to increased glucose in the urine 1
• Urinary tract infections may also occur more frequently 1
• Volume depletion leading to symptoms like dizziness, lightheadedness, and orthostatic hypotension, especially when starting treatment 1

Rare but Serious Side Effects

• Diabetic ketoacidosis, which can occur even with normal blood glucose levels 1
• Increased risk of lower limb amputations and bone fractures in some patients 1
• Fournier's gangrene, a rare but serious infection of the genital area, has been reported 1

Minimizing Side Effects

• Patients should maintain adequate hydration 1
• Practice good genital hygiene 1
• Temporarily stop the medication during severe illness or surgery 1
• Be vigilant for signs of ketoacidosis such as nausea, vomiting, abdominal pain, or unusual fatigue 1

From the FDA Drug Label

Patients treated with JARDIANCE who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with JARDIANCE may be present even if blood glucose levels are less than 250 mg/dL JARDIANCE can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. There have been reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving JARDIANCE. In adult patients, the risk of hypoglycemia may be increased when JARDIANCE is used in combination with insulin secretagogues (e.g., sulfonylurea) or insulin. Reports of necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in patients with diabetes mellitus receiving SGLT2 inhibitors, including JARDIANCE. 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.

The side effects of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors include:

• Ketoacidosis: a serious life-threatening condition requiring urgent hospitalization
• Volume Depletion: intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine
• Acute Kidney Injury: post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis
• Urinary Tract Infections: serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization
• Hypoglycemia: increased risk of hypoglycemia when used in combination with insulin secretagogues or insulin
• Necrotizing Fasciitis of the Perineum (Fournier's Gangrene): a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention
• Genital Mycotic Infections: increased risk for genital mycotic infections
• Hypersensitivity Reactions: postmarketing reports of serious hypersensitivity reactions (e.g., angioedema) 2

From the Research

Side Effects of SGLT2 Inhibitors

The side effects of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors include:

• Urinary tract infections (UTIs) 3, 4
• Genital mycotic infections 5, 3, 6, 4
• Increased risk of hypoglycemia when used with other antidiabetic medications 6
• Euglycemic ketoacidosis 6
• Polyuria 4
• Nausea 4
• Hypotension 4
• Dizziness 4
• Acute coronary event 4
• Worsening of glycemic control status 4
• Rapid deterioration of renal function, especially in patients with evidence of volume depletion and/or receiving other medications which can adversely affect kidney function 4

Benefits and Risks

While SGLT2 inhibitors have been shown to have several benefits, including reducing hemoglobin A1c (HbA1c) levels, body weight, and blood pressure 5, 7, 6, 4, they also carry certain risks. The increased risk of UTIs and genital mycotic infections is a significant concern, particularly in patients receiving dapagliflozin, canagliflozin, and empagliflozin 3. Additionally, the risk of euglycemic ketoacidosis and rapid deterioration of renal function should be carefully monitored 6, 4.

Patient Considerations

Patients receiving SGLT2 inhibitors should be carefully selected and monitored, particularly those with chronic kidney disease, fragile elderly patients, and those receiving other medications that can adversely affect kidney function 6, 4. The benefits and risks of SGLT2 inhibitors should be weighed carefully, and patients should be educated on the potential side effects and the importance of regular monitoring 4.