Sulfonylureas in the Treatment of Diabetes Mellitus

Sulfonylureas are classified as secretagogues which increase the secretion of insulin. Sulfonylureas comprise a large number of oral agents used in the treatment of type 2 diabetes. They work to increase the release of insulin from the pancreas by binding on sulfonylurea-specific receptors on Beta-pancreatic cells, blocking potassium influx through ATP-dependent channels and increasing calcium flow responsible for the secretion of insulin[1]. Increased insulin release helps reduce blood glucose by increasing glucose storage in muscles and peripheral tissues and by inhibiting glucose production in the liver[2].

A commonly prescribed second generation sulfonylurea is Glyburide (DiaBeta). Glyburide is administered orally and has a half-life of about 10 hours. Metabolism takes place in the liver through hydroxylation, producing 4-trans-hydroxyburide and the 3-cis-hydroxyburide, which are ultimately responsible for the long half-life of the drug[3]. Glyburide is 99% bound to plasma proteins and peak serum concentrations are reached in 3-4 hours. Approximately 50% of the drug dose is excreted in the urine while the other 50% is excreted via bile[4].

There is no fixed dosage regimen for Glyburides. A good way to prevent side effects is to start Glyburide at low doses, usually around 2.5-5 mg daily. Usual maintenance dosages range from 1.25-20 mg daily which may be given as a single dose or divided into several doses. Daily doses of more than 20 mg are not recommended and dosage increases should not exceed 2.5 mg per weekly interval[5]. Prolonged use of Glyburide may become ineffective in treating blood glucose levels. If the patient hasn’t reached adequate glycemic control after the first several months of Glyburide treatment, they may be started on insulin treatment[1].

The major adverse effect of Sulfonylureas is hypoglycemia because of its long-acting mechanism. The hypoglycemic effects of sulfonylureas can be potentiated by certain drugs including NSAIDs, ACE inhibitors, fluoxetine, monoamine oxidase inhibitors, and beta-adrenergic blocking agents[5]. Other much less common side effects of sulfonylurea treatment include GI distress, skin reactions, and weight gain[6].

Physical therapists should be aware of the adverse effects of sulfonylurea treatment as they have important clinical implications. Blood glucose levels should be taken before therapy sessions and after to ensure patient safety. During therapy sessions the therapist should be observant for indications of low blood glucose such as anxiety, confusion, headache, and sweating.[6][7] Patients may need to be scheduled before taking their medicine or after they reach the peak serum level to avoid cases of extreme hypoglycemia.

Lastly, patient education is an important aspect of treatment. Patients should be counseled on Glyburide storage at room temperature, avoiding excess heat and moisture[8]. Because hypoglycemia is more likely to occur when there is a caloric deficit, encouraging patients to stick to a meal schedule and eat in the absence of hunger is important to ensure proper insulin and glucose levels. Therapists should also encourage patients to eat prior to physical activity to reduce the risk of hypoglycemia[9].

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  1. 1.0 1.1 Sola, D., Rossi, L., Schianca, G. P. C., Maffioli, P., Bigliocca, M., Mella, R., ... & Derosa, G. (2015). Sulfonylureas and their use in clinical practice. Archives of medical science: AMS, 11(4), 840.
  2. Seino S. Cell signaling in insulin secretion: the molecular targets of ATP, cAMP and sulfonylurea. Diabetologia, 2012; 55: 2096-2108
  3. Rendell, M. (2004). The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs, 64(12), 1339-1358.
  4. Feldman, J. M. (1985). Glyburide: A Second‐generation Sulfonylurea Hypoglycemic Agent: History, Chemistry, Metabolism, Pharmacokinetics, Clinical Use and Adverse Effects. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 5(2), 43-62.
  5. 5.0 5.1 DiaBeta (glyburide) Tablets USP 1.25, 2.5 and 5 mg. (2009). Bridgewater, NJ: sanofi-aventis U.S. LLC.
  6. 6.0 6.1 Ciccone, C. D. (2016). Pharmacology in Rehabilitation.Philadelphia: F.A. Davis Company.
  7. Ahrẻn B. Avoiding hypoglycemia: a key to success for glucose-lowering therapy in type 2 diabetes. Vasc Health Risk Manag. 2013; 9: 155-163
  8. Glyburide. (2017, October 15). Retrieved from MedlinePlus:
  9. Type 2 diabetes. (2018, September 15). Retrieved from Mayo Clinic: