How Do SGLT2 Inhibitors Work?

Sodium-glucose co-transporter 2 or sodium glucose-linked transporter 2 (SGLT2) inhibitors are oral medications used to treat type 2 diabetes mellitus (T2DM) along with a proper diet and exercise. T2DM is a slowly progressive metabolic disorder caused by a combination of genetic and lifestyle factors that promote chronically elevated blood sugar levels. SGLT1 and SGLT2 are a family of glucose transporters found in the intestinal mucosa (enterocytes) of the small intestine and the proximal tubule of the nephron (functional unit of the kidney). SGLT2 inhibitors, also called “gliflozins” inhibit SGLT2 proteins located in the tubules of the kidneys, which are responsible for reabsorbing glucose back into the blood, resulting in high glucose levels in the blood. SGLT2 inhibitors promote glucose excretion in the urine by blocking the action of this protein. Apart from controlling blood sugar, gliflozins provide significant cardiovascular benefits, improve weight loss, and reduce blood pressure in T2DM patients.

SGLT2 inhibitors are also used to reduce the risk of stroke (loss of blood flow to part of the brain), heart attack, or death in people who have T2DM along with heart and blood vessel disease or who have multiple risk factors for developing heart and blood vessel disease.

The kidney filters and reabsorbs glucose which is assisted by active SGLTs and passive glucose transporters. It releases glucose into the circulation by two processes:

• Glycogenolysis: breakdown of glycogen to generate glucose
• Gluconeogenesis: synthesis of free glucose from lactate, pyruvate, and amino acids

SGLT2 inhibitors are administered orally (tablets, extended-release and immediate-release) typically once a day with or without food.

SGLT2 inhibitors work in the following ways:

• They block the action of a protein called “SGLT2” located in the kidney.
• SGLT2 protein is responsible for the reabsorption of sugar (glucose) back into the body from urine.
• SGLT2 inhibitors block this protein and prevent the kidney from reabsorbing glucose from urine and cause more glucose to be excreted from the body through urine which helps in lowering the level of glucose in the blood.

SGLT2 inhibitors are used for the following:

• To reduce blood glucose in adults with T2DM either alone or in combination with metformin or other diabetic medications.
• To reduce the risk of cardiovascular death and hospitalization in adults with heart failure (heart’s inability to pump an adequate supply of blood to the body)
• In adults with chronic kidney disease who are at risk of disease progression

Some of the common side effects include:

• Headache
• Tiredness
• Dryness of mouth
• Flu-like symptoms
• Constipation
• Back pain
• Nausea
• Vomiting
• Flatulence (gas)
• Abdominal discomfort
• Indigestion
• Asthenia (abnormal physical weakness or lack of energy)

Other rare side effects include:

• Hyperkalemia (high blood potassium level)
• Hypotension (low blood pressure)
• Increased urination/thirst
• Increased cholesterol
• Urinary tract infections
• Muscle cramps
• Dizziness (feeling faint, weak, or unsteady)
• Swelling of the arms, hands, feet, ankles, or lower legs
• Female genital mycotic infections (vulvovaginal infections with poorly controlled blood glucose levels)
• Ketoacidosis (a serious complication of diabetes that occurs when the body produces high levels of blood acids called ketones)
• Fournier gangrene (involves an infection in the scrotum which includes the testicles, penis, or perineum)
• Upper respiratory infection
• Nasopharyngitis (an inflammatory attack of the pharynx and nasal cavities)
• Hypoglycemia (low blood sugar level)
  • Sudden sweating
  • Fast heartbeat
  • Blurred vision
  • Tingling in hands/feet

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of SGLT2 inhibitors include:

• Canagliflozin
• Canagliflozin/metformin
• Dapagliflozin
• Dapagliflozin/metformin
• Dapagliflozin/saxagliptin
• Dapagliflozin/saxagliptin/metformin
• Empagliflozin
• Empagliflozin/linagliptin
• Empagliflozin/linagliptin/metformin
• Empagliflozin/metformin
• Ertugliflozin
• Ertugliflozin/metformin
• Ertugliflozin/sitagliptin
• Farxiga
• Glyxambi
• Invokamet
• Invokamet-XR
• Invokana
• Jardiance
• Qtern
• Qternmet XR
• Segluromet
• Steglatro
• Steglujan
• Synjardy
• Synjardy XR
• Trijardy XR
• Xigduo XR