From the Guidelines
SGLT2 inhibitors should be considered as a first-line treatment for patients with type 2 diabetes due to their significant cardiovascular and renal benefits, as demonstrated in recent studies 1.
Key Points
- SGLT2 inhibitors, such as empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin, have been shown to reduce the risk of cardiovascular disease, heart failure hospitalizations, and kidney function decline in patients with type 2 diabetes 1.
- These medications work by preventing glucose reabsorption in the kidneys, leading to increased glucose excretion in urine, and have been found to have beneficial effects on mortality, cardiovascular outcomes, and renal outcomes 1.
- Common side effects of SGLT2 inhibitors include genital yeast infections, urinary tract infections, and volume depletion, and patients should be advised to maintain adequate hydration and practice good genital hygiene 1.
- SGLT2 inhibitors should be used cautiously in older adults, particularly those who are frail or prone to orthostasis, and should be temporarily discontinued during acute illness, surgery, or situations with reduced oral intake to prevent diabetic ketoacidosis 1.
Dosage and Administration
- The typical starting dose for empagliflozin is 10 mg once daily, dapagliflozin 5-10 mg once daily, canagliflozin 100 mg once daily, and ertugliflozin 5 mg once daily.
Special Considerations
- SGLT2 inhibitors may cause clinically significant volume depletion, and should be used with caution in individuals at elevated risk, such as older adults 1.
- These medications may also increase the risk of urinary tract infections, and should be used with caution in people with recurrent or severe urinary tract infections 1.
- Emerging data suggests that SGLT2 inhibitor use may cause an increase in osteoporotic bone fractures, and clinicians should consider minimizing SGLT2 inhibitor use in older adults at high fracture risk 1.
From the FDA Drug Label
Dapagliflozin, an inhibitor of SGLT2, is described chemically as D-glucitol, 1,5-anhydro-1-C-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-, (1S)-, compounded with (2S)-1,2-propanediol, hydrate (1:1:1). Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Dapagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, dapagliflozin reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion
SGLP inhibitors are a class of drugs that inhibit the sodium-glucose cotransporter 2 (SGLT2) in the kidneys.
- Dapagliflozin is an example of an SGLT2 inhibitor.
- Mechanism of action: Dapagliflozin works by inhibiting SGLT2, reducing the reabsorption of filtered glucose and promoting urinary glucose excretion.
- Key points:
- Inhibits SGLT2 in the proximal renal tubules
- Reduces reabsorption of filtered glucose
- Promotes urinary glucose excretion
- Also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule 2
From the Research
SGLT2 Inhibitors Overview
- SGLT2 inhibitors are a new class of medications for the treatment of type 2 diabetes, acting by increasing urinary glucose excretion 3
- They are effective in improving glycaemic control, promoting weight loss, and lowering blood pressure, with a low risk of hypoglycemia 3, 4, 5
Mechanism of Action
- SGLT2 inhibitors work by blocking glucose reabsorption by the kidneys, leading to increased glucosuria 3, 5, 6
- This mechanism of action is insulin-independent, allowing for combination with other antidiabetic medications, including insulin, with minimal risk of hypoglycemia 5
Clinical Efficacy
- SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, have been shown to be effective in improving glycaemic control, with reductions in hemoglobin A1C and fasting plasma glucose 7, 3, 4
- They also provide additional benefits, including weight loss and blood pressure reduction 7, 3, 4, 5
Cardiovascular Benefits
- Some SGLT2 inhibitors, such as canagliflozin and empagliflozin, have shown cardiovascular benefits, including reduced risk of cardiovascular death in patients with type 2 diabetes 6
- Dapagliflozin has also been shown to reduce the rate of cardiovascular death or hospitalization for heart failure, and possibly reduce progression of renal disease 7