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Empagliflozin: Potential New Approach to Treating T2DM

Empagliflozin is proving to be a strong proponent for monotherapy in patients with T2DM.

Empagliflozin–an inhibitor of sodium-glucose co-transporter 2 (SGLT-2)–was more recently approved for patients with type 2 diabetes to help lower blood glucose in adults, alongside diet and exercise. Metformin has long been the mainstay medication for patients with type 2 diabetes. Typically a patient will begin on metformin monotherapy due to its ability to reduce hepatic glucose production through inhibition of gluconeogenesis and increase glucose uptake in peripheral tissue. However, for most patients, metformin alone usually fails to maintain appropriate glycemic control. When this glycemic control can no longer be maintained via monotherapy, additional medications are added on to a patient’s regimen in order to further assist with controlling their blood glucose.

The kidney has become a prime focus for patients with diabetes and therapy targeted to the kidney is essential in order to treat diabetes in general. About 90 percent of glucose is filtered by the kidney and is then reabsorbed via the sodium glucose cotransporter 2 (SGLT-2), which is located in the proximal tubule of the nephron. SGLT-2 inhibitors have hence become a novel oral anti-diabetic agent due to their ability to reduce glucose reabsorption, increase urinary glucose excretion and reduce hyperglycemia independent of beta-cell function and insulin resistance.

In a recent double-blind extension, phase three randomized controlled trial, researchers sought to investigate the long-term efficacy and safety of empagliflozin monotherapy compared to sitagliptin in patients who are drug-naïve with type 2 diabetes. Of nearly 899 patients who were randomized and given either empagliflozin 10 milligrams, empagliflozin 25 milligrams, a placebo or sitagliptin 100 milligrams once daily for 24 weeks, nearly 615 were able to continue with the trial for greater than 52 weeks. What they found was that there was a significant decrease in overall HbA1c, decrease in weight and a decrease in systolic blood pressure in patients who received 25 milligrams of empagliflozin compared to sitagliptin. Overall, empagliflozin monotherapy was significantly more effective than its counterpart and led to a sustained reduction in HbA1c and weight. Hypoglycemia presents a significant safety risk for patients with type 2 diabetes, which can have detrimental effects on a patient. Empagliflozin therapy reduces the risk of patients getting to that state, which is an important safety attribute of the drug when compared to sitagliptin.

Continued research is being done presently to gauge the extent of the therapeutic value of empagliflozin, but the results in present research clearly outline the incredible glycemic control attained with monotherapy alone. With all the benefits that may potentially be obtained with the drug, many wonder whether the treatment algorithms for patients with type 2 diabetes should be updated to include SGLT-2 inhibitors as first-line therapy. Though it may be difficult to usurp metformin, empagliflozin has significantly made an impact on HbA1c reduction and future research will pave the way to make it a potential first-line agent for the treatment of type 2 diabetes.

Practice Pearls:

  • Empagliflozin provides an effective reduction in HbA1c in patients with type 2 diabetes.
  • Compared to sitagliptin, the safety profile of empagliflozin is significantly better.
  • Current research and findings on the use of empagliflozin are slowly making it a plausible proponent for monotherapy in patients with type 2 diabetes.

Researched and prepared by Javeria Fayyaz, Doctor of Pharmacy Candidate LECOM College of Pharmacy, reviewed by Dave Joffe, BSPharm, CDE

 

Roden, Michael. “Safety, Tolerability and Effects on Cardiometabolic Risk Factors of Empagliflozin Monotherapy in Drug-naïve Patients With Type 2 Diabetes.” Cardiovascular Diabetology 14 (2015): n. pag. Web. 20 Feb. 2016.

“Empagliflozin Cuts Cardiovascular Deaths in Landmark Trial EMPA-REG OUTCOME Coverage.” National Diabetes Education Initiative. N.p., n.d. Web. 20 Feb. 2016.