Sulfonylureas

Type 2 diabetes is a widespread metabolic disease leading to one of the greatest burden of chronic disease around the world. Although oral hypoglycaemic drugs are widely used nowadays, in the treatment of the type 2 diabetes, many of the medicines pose serious threat to the body. This summary would focus on the four classes of the hypoglycemic drugs: – Sulfonylureas, Metformin, Thiazolidinediones and Alpha-glucosidase inhibitors. Sulfonylureas works mainly by the stimulation of the insulin, which is done by increasing the responsiveness of the Beta cells to both the glucose and the non-glucose secretagogues, leading to more insulin production. The main side effect of this medicine is hypoglycemia. Some of the medicines under this class of drugs is Repaglinide, that has been newly approved by the Food and Drug Administration, the structurally differs from Sulphonylurea but shows the same mode of action. Another similar drug is Natiglinide that acts on the initial phase of the release of insulin than the late phase.  It makes this medicine more effective in patients suffering from impaired glucose tolerance..  

Another class of hypoglycemic drugs is Metformin that is reported to have been lowering the fasting blood glucose concentrations by 20 percent approximately. Metformin does not stimulate the secretion of the insulin, but the increases the action of the insulin. Metformin is used in obese patients suffering from Type 2 diabetes, as it contributes to weight stabilization (Rena, Pearson & Sakamoto, 2013).. One of the advantages of using Metformin over Sulphonylureas is that, there is less chance of causing hypoglycemia and it also displays lipid lowering activity causing a significant lessening in the serum triglycerides, concentration of the serum low-density lipoprotein (LDL), and an increase in the concentration of serum high-density lipoprotein (HDL) cholesterol. Some of the side effects associated with metformin are some gastrointestinal disturbances and lactic acidosis under predisposing factors such as heart failure, renal insufficiency, past history of the lactic acidosis, hypoxic stress and acute illness. Potential drug interaction might occur between Cimetidine and Metformin causing hypoglycemia in the patients (Tornio et al., 2013). This risk has increased over the years as Cimetidine is now available as over the counter medicine. The thiazolidinediones increases the action of the insulin by the redistribution of the fat. The redistribution takes place from the visceral component to the subcutaneous compartment, as visceral fat is linked to insulin resistance (Cariou, Charbonnel & Staels, 2012).. Thiazolidinediones had shown its effectiveness in a large study consisting of 284 patients, but the product had been removed from the market, due to the severe liver injury in some of the patients treated with Rezulin (Cariou, Charbonnel & Staels, 2012). Nowadays, safer agents such as Avandia and Actos are in use, due to their lower side effects.  In comparison to the Thiazolidinediones, the alpha-glucosidase inhibitors like Miglitol and Acarbose displays less side effects, as they restrict the enzymes of the upper gastrointestinal part, that causes the conversion of the dietary starch and the other complex carbohydrates into simple carbohydrates. Hence, glucose is absorbed slowly after the meal. The alpha-glucosidase inhibitors have been found to be causing a marked reduction in the amount of the excursion of the glucose and HbA1c, causing a possible drop in the nocturnal hypoglycemia (Derosa & Maffioli, 2012). Some of the side effects of these classes of drugs are diarrhea and flatulence.

However it should be mentioned that pharmacological treatment of diabetes is associated with several side effects and drug interactions. Hence, adherence to suitable diet and physical exercise are still considered to be most effective and these drugs are only approved for those not responding to diet, exercise and weight reduction. These are not approved for the pregnant women due to their adverse effects.  

References

Cariou, B., Charbonnel, B., & Staels, B. (2012). Thiazolidinediones and PPARγ agonists: time for a reassessment. Trends in Endocrinology & Metabolism, 23(5), 205-215.

Derosa, G., & Maffioli, P. (2012). α-Glucosidase inhibitors and their use in clinical practice. Archives of medical science: AMS, 8(5), 899.

Rena, G., Pearson, E. R., & Sakamoto, K. (2013). Molecular mechanism of action of metformin: old or new insights?. Diabetologia, 56(9), 1898-1906.

Tornio, A., Niemi, M., Neuvonen, P. J., & Backman, J. T. (2012). Drug interactions with oral antidiabetic agents: pharmacokinetic mechanisms and clinical implications. Trends in pharmacological sciences, 33(6), 312-322.