What are the contraindications for Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors?

From the Guidelines

SGLT2 inhibitors are contraindicated in patients with severe renal impairment (eGFR below 30 ml/min/1.73m²), those on dialysis, pregnant or breastfeeding women, and individuals with a history of severe hypersensitivity reaction to the drug. According to the most recent and highest quality study 1, SGLT2 inhibitors should not be used in patients with eGFR <30 for glucose lowering, and are contraindicated in dialysis. The study also recommends that dapagliflozin and canagliflozin should not be initiated in patients with eGFR <25 and <30, respectively.

Key Contraindications

• Severe renal impairment (eGFR below 30 ml/min/1.73m²)
• Patients on dialysis
• Pregnant or breastfeeding women
• History of severe hypersensitivity reaction to the drug
• History of severe genital mycotic infections or recurrent urinary tract infections

Important Considerations

• SGLT2 inhibitors should be used with caution in patients with prior amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers or soft tissue infections 1.
• The medications may contribute to intravascular volume contraction, and patients should be monitored for signs of dehydration 1.
• Patients with a history of diabetic ketoacidosis should use these medications cautiously, and the medications should be temporarily discontinued before major surgical procedures and during acute serious medical illnesses due to increased risk of volume depletion and ketoacidosis during these periods.

Dose Modifications

• For patients with eGFR 30 to 59 ml/min/1.73m², the maximum dose of canagliflozin is 100 mg daily 1.
• For patients with eGFR <45 ml/min/1.73m², dapagliflozin is not recommended for glycemic control, and empagliflozin is not recommended for glycemic control in patients with eGFR <45 mL/min/1.73m² 1.

From the FDA Drug Label

CONTRAINDICATIONS History of serious hypersensitivity reaction to empagliflozin or any of the excipients in JARDIANCE (4) Severe renal impairment, end-stage renal disease, or dialysis (4)

CONTRAINDICATIONS History of serious hypersensitivity reaction to dapagliflozin or any of the excipients in DAPAGLIFLOZIN TABLETS (4)

The contraindications for SGLT2 inhibitors, such as empagliflozin and dapagliflozin, include:

• History of serious hypersensitivity reaction to the medication or its excipients
• Severe renal impairment, end-stage renal disease, or dialysis 2 Note that dapagliflozin is also not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2, as it is likely to be ineffective in this setting based upon its mechanism of action 3

From the Research

Contraindications of SGLT2 Inhibitors

• The provided studies do not explicitly state contraindications for SGLT2 inhibitors, but they do discuss the effects of these inhibitors on patients with chronic kidney disease (CKD) and diabetes 4, 5, 6, 7, 8.
• According to the studies, SGLT2 inhibitors can be beneficial for patients with CKD and diabetes, reducing the risk of kidney failure, cardiovascular events, and all-cause death 5, 6, 7, 8.
• However, the studies also mention that the effects of SGLT2 inhibitors may vary depending on the patient's baseline characteristics, such as estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) 4, 6, 7.
• The studies suggest that SGLT2 inhibitors may be less effective or have a higher risk of adverse events in patients with certain conditions, such as:
  • eGFR < 30 mL/min/1.73 m2 5, 6
  • Atherosclerotic cardiovascular disease 6
  • Heart failure 6, 8
• However, these findings are not necessarily contraindications, and the decision to prescribe SGLT2 inhibitors should be made on a case-by-case basis, taking into account the individual patient's characteristics and medical history.

Special Considerations

• The studies highlight the importance of careful patient selection and monitoring when prescribing SGLT2 inhibitors, particularly in patients with CKD and diabetes 4, 5, 6, 7, 8.
• Clinicians should be aware of the potential benefits and risks of SGLT2 inhibitors in different patient populations and adjust their treatment strategies accordingly.
• Further research is needed to fully understand the effects of SGLT2 inhibitors in patients with CKD and diabetes, particularly in those with more advanced kidney disease or other comorbidities.