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Empagliflozin Potentially Protects Pancreatic Beta-cells in T1DM

New animal study shows the effects of empagliflozin, an SGLT-2 inhibitor, on the pancreatic cells of mice.  

The results of a new study on potential effects of empagliflozin for type 1 diabetes indicate empagliflozin may play a role in preserving beta cell regeneration and improving blood glucose control in type 1 diabetes patients.

Type 1 diabetes mellitus is a disease state that represents 5-10% of patients with diabetes in the United States. Type 1 diabetics are required to be on insulin, whereas, in type 2 diabetics insulin therapy is reserved for more severe cases. Type 1 diabetes is an autoimmune disorder that attacks the pancreatic beta cells, leading to severe insulin deficiency. Unfortunately, there is no known cure currently for type 1 diabetics. Due to their reliance on insulin, type 1 diabetics are at much greater risk of hypoglycemia. This creates great interest in the development of a non-insulin therapy for the management of type 1 diabetes.

A drug of interest for this research has been sodium glucose cotransporters, which are involved in glucose reabsorption in the kidney. It is estimated that a healthy adult filters 160 to 180 grams of glucose per day through their kidneys. The glucose is then reabsorbed back into the bloodstream in the renal proximal convoluted tubules. SGLT-2 inhibitors have also been shown to confer other benefits, such as lowering blood pressure. SGLT-2 inhibitors lower systolic blood pressure by 3-5 mmHg and diastolic blood pressure by approximately 2 mmHg. Though the decrease in blood pressure is small, it may confer long term cardiovascular benefits as well as improve glycemic control and weight loss. It has also been shown in a previous study in type 2 diabetic mice, that by knocking out the SGLT-2 genes the mice were protected from hyperglycemia and glucose intolerance even when fed a high fat diet.

There is hope that SGLT-2 inhibitors can provide benefits to type 1 diabetics as well due to their mechanism of action. SGLT-2 inhibitors have been shown to consistently improve glycemic control and pancreatic function. There is hope to reduce patient’s A1c, fasting blood glucose, body weight, and total daily insulin dose without having the risk of hypoglycemia. There is also speculative data that shows renal protection by reducing the glomerular hyperfiltration of diabetes.

Researchers conducted an animal model experiment with 10-week-old mice in which type 1 diabetes was induced using injections of streptozotocin. The mice were given empagliflozin 3 mg/kg, empagliflozin 10 mg/kg, or placebo orally once daily for 8 days. The results of the study showed that mice treated with empagliflozin showed significantly improved glucose tolerance. The study also found that these mice also required lower doses of insulin, thus putting them at lower risk of hypoglycemia. The most interesting result from the study was that both mRNA and serum insulin levels in type 1 diabetes mice were significantly higher after 8 day treatment with empagliflozin. This increase can be attributed to the preservation of beta cell due to the reduction of beta cell apoptosis as well as the stimulation of beta cell proliferation.

Overall, the clinical animal trial showed that treatment with empagliflozin improves beta cell function and mass in the pancreatic islet. It’s theorized that this is due to the reduction of oxidative stress on the beta cells, which confers beta cell protection and higher insulin secretion. The study shows hope that with the preservation of endogenous insulin production type 1 diabetes patients can reduce their use of insulin therapy, which puts them at lower risk of hypoglycemia.

Practice Pearls:

  • Type 1 diabetes is an autoimmune disorder that leads to the destruction of the pancreatic beta cells. This destruction of pancreatic cells leads the patient to become insulin dependent.
  • SGLT-2 inhibitors are the newest class of drugs that inhibits the reabsorption of glucose in the kidney. By inhibiting the reabsorption of glucose, SGLT-2 lowers blood glucose levels and prevents hyperglycemia.
  • Empagliflozin used in induced type 1 diabetic mice showed improved beta cell function and mass. These mice also required less insulin which lowers their risk of becoming hypoglycemic.

 

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

Cheng STW, Chen L, Li SYT, Mayoux E, Leung PS (2016) The Effects of Empagliflozin, an SGLT2 Inhibitor, on Pancreatic β-Cell Mass and Glucose Homeostasis in Type 1 Diabetes. PLoS ONE 11(1): e0147391. doi:10.1371/journal.pone.0147391

Vargas R, Repke JT, Ural SH. Type 1 diabetes mellitus and pregnancy. Rev Obstet Gynecol. 2010; 3(3): 92–100. pmid:21364860

Vallon V, Platt KA, Cunard R, Schroth J, Whaley J, Thomson SC, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011; 22(1): 104–112. pmid:20616166 doi: 10.1681/ASN.2010030246