SGLT-2 Inhibitors – Mechanism of Action

12 Dec 2017

SGLT-2 inhibitors Inhibit the Na-glucose co-transporter 2 (SGLT-2) in the kidney to reduce glucose reabsorption, resulting in increased urinary glucose excretion, and lower plasma glucose. SGLT-2 is expressed in the proximal tubule and mediates reabsorption of ~90% of filtered glucose.


Mechanism of action:

  • Indications:
    • Type 2 diabetes
    • New drug: currently mainly used as adjunct therapy in patients not meeting their glycemic goal with other agents
  • Contraindications:
    • Severe renal impairment – its efficacy depends on renal function. While it can be prescribed to patients with moderate renal impairment (GFR between 45 & 60 ml/min), it should not be prescribed to patients with more severe renal impairment.
    • NOT recommended for treatment of type 1 diabetes or treatment of diabetic ketoacidosis
  • NOTE: This is a relatively new drug class that lacks long-term safety & efficacy data
    • Urinary Tract Infections (the most common side effect for this drug class); increased glucose in the urine can worsen yeast or bacterial infections commonly associated with diabetes.
    • Hypotension (2%)(due to intravascular volume contraction) – most common in patients with impaired renal function, elderly or on patients on drugs that interfere with the RAS system (ACE inhibitors, ARBs)
    • Dehydration (mainly in elderly, or if combined with diuretics)
    • Hyperkalemia (>10%)
    • Increased LDL (dose related)
    • Ketoacidosis (all SGLT2 inhibitors)