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SGLT2 Inhibitors: Effects, Uses & Side Effects

SGLT2 inhibitors are medications used to treat type 2 diabetes, heart failure, and chronic kidney disease. They lower blood sugar by acting on the kidneys.

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Things worth knowing about "SGLT2 inhibitors"

SGLT2 inhibitors are medications used to treat type 2 diabetes, heart failure, and chronic kidney disease. They lower blood sugar by acting on the kidneys.

What Are SGLT2 Inhibitors?

SGLT2 inhibitors (also called gliflozins or sodium-glucose cotransporter 2 inhibitors) are a class of medications originally developed to treat type 2 diabetes mellitus. In recent years, they have also become an important treatment option for heart failure and chronic kidney disease (CKD). Well-known active substances in this class include empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin.

Mechanism of Action

SGLT2 inhibitors block the sodium-glucose cotransporter 2 (SGLT2), a transport protein located in the kidney tubules. Under normal circumstances, this transporter reabsorbs nearly all glucose filtered from the blood back into circulation. By blocking SGLT2, more glucose is excreted through the urine, which lowers blood glucose levels.

In addition to lowering blood sugar, SGLT2 inhibitors also provide:

Blood pressure reduction through increased excretion of sodium and water (osmotic diuresis)
Weight loss due to caloric loss via the urine
Cardioprotective effects (heart protection) through multiple mechanisms
Nephroprotective effects (kidney protection) by reducing intraglomerular pressure

Indications

SGLT2 inhibitors are approved for the following conditions:

Type 2 diabetes mellitus: As monotherapy or combination therapy to lower blood glucose and HbA1c levels
Heart failure: Both with reduced and preserved ejection fraction (HFrEF and HFpEF) – regardless of diabetes status
Chronic kidney disease (CKD): To slow the progression of kidney damage

Dosage and Administration

SGLT2 inhibitors are typically taken once daily by mouth, usually in the morning, with or without food. The exact dosage depends on the specific drug and indication and must always be determined by a physician. Examples:

Empagliflozin: 10 mg or 25 mg daily
Dapagliflozin: 10 mg daily
Canagliflozin: 100 mg or 300 mg daily

Side Effects

Like all medications, SGLT2 inhibitors can cause side effects. The most common include:

Genital yeast infections (particularly common, as higher glucose levels in the urine promote fungal growth)
Urinary tract infections
Increased urination (polyuria due to osmotic diuresis)
Low blood pressure (hypotension), especially in elderly patients or those also taking diuretics
Diabetic ketoacidosis (rare but serious complication, even at near-normal blood glucose levels)
Fournier gangrene (very rare but severe necrotizing infection of the genital area)
Increased fracture risk (particularly with canagliflozin)

Contraindications

SGLT2 inhibitors should not be used in patients with:

Type 1 diabetes mellitus (except under specific circumstances with medical supervision)
Severe kidney impairment (eGFR thresholds vary by drug)
Pregnancy and breastfeeding
Known hypersensitivity to the active substance

Clinical Significance and Key Studies

Large clinical trials such as EMPA-REG OUTCOME, DAPA-HF, and CREDENCE have demonstrated that SGLT2 inhibitors do more than lower blood sugar – they also significantly reduce the risk of heart attack, stroke, hospitalization for heart failure, and the progression of kidney disease. These findings have fundamentally changed treatment guidelines for diabetes, heart failure, and chronic kidney disease.

References

Zinman B et al. – Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME). New England Journal of Medicine, 2015; 373:2117–2128.
McMurray JJV et al. – Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF). New England Journal of Medicine, 2019; 381:1995–2008.
European Medicines Agency (EMA) – Product information on SGLT2 inhibitors. Available at: https://www.ema.europa.eu

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