What they are
SGLT2 inhibitors are a class of medication that block a protein in the kidney called Sodium-Glucose Cotransporter 2 (SGLT2), which normally reabsorbs glucose back into the bloodstream. Blocking SGLT2 causes the kidneys to excrete extra glucose into the urine, lowering blood sugar.
Common SGLT2 inhibitors include:
- Dapagliflozin (Farxiga)
- Empagliflozin (Jardiance)
- Canagliflozin (Invokana)
- Ertugliflozin (Steglatro)
They were originally approved for type 2 diabetes, but extensive research over the past decade has revealed substantial benefits beyond glucose control.
Why nephrologists use them
SGLT2 inhibitors slow the progression of chronic kidney disease in patients both with and without diabetes. In landmark clinical trials (DAPA-CKD, EMPA-KIDNEY, CREDENCE), they reduced the combined risk of kidney failure, heart failure hospitalization, and cardiovascular death by 25–40%. The benefit appears across a wide range of patients, including those with CKD from causes other than diabetes.
Key effects:
- Reduce protein loss in the urine
- Lower the pressure inside the kidney's filtering units
- Reduce blood pressure modestly
- Promote modest weight loss
- Reduce hospitalization for heart failure
These medications are now considered foundational therapy for most patients with CKD and proteinuria, alongside ACE inhibitors or ARBs.
| Benefit | Detail |
|---|---|
| Slows kidney decline | In diabetic and non-diabetic kidney disease alike |
| Protects the heart | Fewer heart-failure hospitalizations |
| Modest extras | Small improvements in weight and blood pressure |
Who benefits
SGLT2 inhibitors are particularly recommended for:
- CKD with proteinuria (with or without diabetes)
- Type 2 diabetes with kidney or cardiovascular disease
- Heart failure (with or without diabetes)
Side effects to know about
Most side effects are manageable, but a few warrant attention:
- Genital yeast infections (women) and balanitis (men): the most common side effect, related to glucose in the urine. Usually treatable with topical antifungal medication. Good genital hygiene reduces risk.
- Mild dehydration and lightheadedness: especially when first starting or in hot weather. Adequate fluid intake helps.
- Urinary tract infections: slightly increased risk in some patients.
- Euglycemic diabetic ketoacidosis (rare but serious): high ketones in the blood despite near-normal blood sugar. Symptoms include nausea, vomiting, abdominal pain, and rapid breathing. Stop the medication and seek emergency care if these symptoms develop. Especially important to hold around surgery, severe illness, or prolonged fasting.
- Initial creatinine bump: a small early rise in serum creatinine is expected and not a reason to stop. Larger or sustained rises warrant evaluation.
Safety in chronic kidney disease
Most questions we get about SGLT2 inhibitors are really one question: is a drug that acts on the kidney safe for a kidney that is already struggling? These are among the better-studied medications in nephrology, and the trials that established their benefit were run specifically in people with reduced kidney function.
The early eGFR dip is expected. In the first two to six weeks, serum creatinine usually rises slightly and eGFR falls by a few points. This is a change in pressure inside the kidney's filtering units, not injury — the same mechanism that makes ACE inhibitors and ARBs protective. It stabilises, and in the trials the patients who had this dip went on to lose kidney function more slowly than those who did not. A dip is not a reason to stop. A large or continuing fall is worth a call.
Starting and continuing at a low eGFR. KDIGO 2024 supports starting an SGLT2 inhibitor at an eGFR of about 20 or above. Once you are established on one, it is reasonable to keep going even if your eGFR later drifts below that — through to dialysis or transplant. The kidney and heart protection persists at low eGFR; what fades is the blood-sugar-lowering effect, which is why the medication may stay on your list even when it is no longer doing much for your glucose.
Fluid balance and your other medications. Because these drugs push glucose and sodium into the urine, water follows. That mild diuretic-like effect is strongest early on. If you take a loop diuretic such as furosemide, your clinician may lower the dose when you start, and may ask you to watch for lightheadedness on standing.
Low blood sugar is uncommon on its own. An SGLT2 inhibitor by itself rarely causes hypoglycemia. The risk rises when it is combined with insulin or a sulfonylurea such as glipizide, and those doses are sometimes adjusted at the same time.
Who should usually not take one. They are not used in type 1 diabetes, in anyone with a history of diabetic ketoacidosis, or during pregnancy and breastfeeding. Recurrent genital or urinary infections, and any history of Fournier gangrene, also change the calculation. Tell your nephrologist about any of these before starting.
Monitoring
After starting, your nephrologist will typically recheck kidney function and electrolytes within 4–6 weeks, then every 3–6 months. That first recheck is mainly to confirm the expected eGFR dip has settled rather than kept going, and to see whether any diuretic dose needs adjusting.