Sodium-glucose co-transporter 2 (SGLT2) is a channel in the kidney cells that reabsorb sodium and sugar. SGLT2 inhibitors are a new class of medications that inhibit these channels and result in decreased absorption of filtered sugar by the kidney as well as sodium. As a result, there is loss of sugar, sodium and water in the urine and thereby modestly lower elevated blood glucose levels in patients with type 2 diabetes. The ability to lower blood glucose and hemoglobin A1C levels is limited by the filtered load of glucose and the diuresis that is caused by this therapy.

SGLT2 inhibitors only lower plasma glucose levels by blocking reabsorption of filtered glucose, which falls as blood levels of sugar fall. Thus, they do not usually cause hypoglycemia or low blood sugars. SGLT2 inhibitors can help modestly decrease blood pressure and weight but loss of extra salt and calories from sugar loss.

SGLT2 inhibitors are considered as second line therapy for the majority of patients with type 2 diabetes after diet, weight reduction, exercise, and metformin (in the absence of contraindications).

SGLT2 inhibitors have been studied in many different outcome trials with beneficial results. There are several of them on the market either alone or in combination form. The most common ones are empagliflozin (Jardiance), canagliflozin (Invokana), dapagliflozin (Farxiga), ertugliflozin (Steglatro). Empagliflozin is the preferred SGLT2 inhibitor in a patient with type 2 diabetes and atherosclerotic Cardiovascular Disease based on the results of the trial using this drug. In patients with type 2 diabetes and heart failure, all SGLT2 inhibitors have shown beneficial effects; choice of agent is primarily dictated by the patient's insurance formulary restrictions, and copay costs and physician preference. In patients without Cardiovascular Disease, choice of SGLT2 inhibitor is also often dictated by cost and insurer formulary coverage.

In patient with Type 2 Diabetes and heart failure with reduced ejection fraction all SGLT2 inhibitor can be used as secondary therapy. But in those with heart failure without diabetes dapagliflozin or empagliflozin are preferred based on studies.

Extra caution should be carried and sometimes avoiding this class of medicines altogether in patients with frequent bacterial urinary tract infections or genitourinary yeast infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis (pancreatic insufficiency, drug or alcohol abuse disorder) because of increased risk while using these agents

SGLT2 inhibitors have been studied in diabetic and non-diabetic kidney disease with persistent protein leakage in the urine despite maximum doses of ACE inhibitors (like lisinopril) or Angiotensin Receptor Blockers (like losartan). SGLT2i delays progression of kidney disease and development of End Stage Kidney Disease and are recommended to start in patients who have maximized their ACE inhibitors or Angiotensin Receptor blockers and have Diabetic Kidney Disease with eGFR above 25 ml/min and Albumin Creatinine ratio (ACR) above 200mg/g (dapagliflozin) or above 30 ml/min and ACR above 300 mg/g (canagliflozin). In DAPA-CKD Trial patients with CKD without diabetes and proteinuria despite maximum ACE or ARB were studies. Dapagliflozin reduced progression of kidney disease in this population as well. Once started on SGLT2i, they can be continued if your GFR falls below 25.

If you have kidney disease with significant protein leakage in the urine ask your kidney physician if SGLT2 inhibitors are right for you. SGLT2 inhibitors are not appropriate for use in patients with type 1 diabetes and kidney disease or those with polycystic kidney disease as they were all excluded from studies.