From the Guidelines
The safest SGLT inhibitors are generally considered to be empagliflozin (Jardiance), dapagliflozin (Farxiga), and canagliflozin (Invokana), with empagliflozin often cited as having the strongest cardiovascular safety profile. These medications are typically started at lower doses (empagliflozin 10mg daily, dapagliflozin 5mg daily, or canagliflozin 100mg daily) and may be increased if needed and tolerated. All SGLT inhibitors work by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine, which helps lower blood sugar levels.
While generally safe, patients should be aware of potential side effects including:
- Genital mycotic infections
- Urinary tract infections
- Volume depletion These medications should be used cautiously in patients with reduced kidney function, and patients should be well-hydrated and monitored for ketoacidosis, particularly when starting therapy. Patients with type 1 diabetes should generally avoid SGLT inhibitors due to increased risk of diabetic ketoacidosis. For optimal safety, regular monitoring of kidney function, maintaining adequate hydration, and practicing good genital hygiene can help minimize risks while benefiting from these medications' glucose-lowering, cardiovascular, and renal protective effects 1.
Key considerations for the use of SGLT inhibitors include:
- Initiating therapy at a low dose and titrating as needed and tolerated
- Monitoring for signs and symptoms of ketoacidosis, particularly in patients with type 1 diabetes
- Maintaining adequate hydration to minimize the risk of volume depletion
- Practicing good genital hygiene to reduce the risk of genital mycotic infections
- Regularly monitoring kidney function to adjust therapy as needed.
Overall, the benefits of SGLT inhibitors in reducing cardiovascular risk and improving glycemic control make them a valuable treatment option for patients with type 2 diabetes, and their safety profile is generally favorable when used appropriately 1.
From the Research
Safe SGLT Inhibitors
The safety of Sodium-Glucose Linked Transporter (SGLT) inhibitors has been evaluated in several studies. Some of the safest SGLT inhibitors include:
- Empagliflozin: shown to reduce the risk of heart failure hospitalization and cardiovascular death in patients with type 2 diabetes mellitus (T2DM) 2, 3, 4, 5
- Dapagliflozin: reported to reduce heart failure hospitalization and cardiovascular death in patients with heart failure with reduced ejection fraction (HFrEF), regardless of the existence or absence of T2DM 2, 4
- Canagliflozin: found to reduce glycated hemoglobin, with a minimal risk of hypoglycemia, and exert favorable effects beyond glucose control, including consistent body weight, blood pressure, and serum uric acid reductions 3, 6
- Sotagliflozin: also reported to reduce heart failure hospitalization and cardiovascular death in patients with HFrEF, regardless of the existence or absence of T2DM 2
- Ertugliflozin: shown to decrease the risk of heart failure hospitalization across a range of patients with and without atherosclerotic cardiovascular disease in patients with T2DM 2
Adverse Events
Common adverse events associated with SGLT inhibitors include:
- Genital mycotic infections: approximately 10% of women treated with canagliflozin experienced a genital mycotic infection compared with 3% treated with placebo 6
- Urinary tract infections: approximately 9% of women treated with canagliflozin reported a urinary tract infection compared with 7% treated with placebo 6
- Increased urination: a common adverse event observed with SGLT inhibitors 6
- Volume depletion: a rare adverse event associated with SGLT inhibitors 3
- Ketoacidosis and bone fractures: a concern that has been raised, which deserves caution and further evaluation 3
Clinical Applications
SGLT inhibitors have been shown to offer cardiovascular and kidney protection in both diabetic and non-diabetic chronic kidney disease (CKD) patients, and additionally, improve glycemic control in T2DM, making them a first-line therapy for CKD independent of diabetic status 4, 5