Diabetes and Antidiabetic Drugs

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This chapter is a comprehensive account of diabetes and the medicinal chemistry of antidiabetic drugs. It provides the mechanism of disease progression and drug action and detailed structure-activity relationships (SAR) of antidiabetic drugs to give the knowledge base for pharmacists. After studying this chapter, students will be able to: • Discuss the epidemiology and etiology of diabetes. • Describe the clinical features of diabetes and differentiate between type I and type II diabetes. • Discuss various risk factors and corresponding mechanisms responsible for the development of diabetes.• Review biosynthesis of insulin, its metabolic outcomes, regulation of insulin secretion, and insulin signaling.• Explain in detail the pathophysiologic mechanisms responsible for the clinical features of diabetes. • Evaluate the clinical role of natural human insulin and commercially available other insulin products and discuss its mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications, and precautions. • Discuss the mechanism of action, pharmacokinetics, adverse effects, motor complications, drug interactions, contraindications, and precautions for each class of antidiabetic drugs listed below. o Sulfonylureas: tolbutamide (Orinase® ), tolazamide (Tolinase® ), chlorpropamide (Diabinese® ), and acetohexamide (Dymelor® ), glyburide (Diabeta® ), glipizide (Glucotrol® ), and glimepiride (Amaryl® ). o Meglitinides: repaglinide (Prandin® ), nateglinide (Starlix® ). o Biguanides: metformin (Glucophage® , Glucophage XR).o Peroxisome proliferator activated receptor (PPAR) agonists/Thiazolidinediones: pioglitazone (Actos® ), rosiglitazone (Avandia® ).o Alpha glucosidase inhibitors: acarbose (Precose® ). o Glucagon-like peptide-1 (GLP-1) agonists: dulaglutide (Trulicity® ), exenatide (Bydureon® , Byetta® ), liraglutide (Victoza® ), lixisenatide (Adlyxin® ), semalgutide (Ozempic® , Rybelsus® ). o Dipeptidyl peptidase-4 (DPP-4) inhibitors: alogliptin (Nesina® ), linagliptin (Tradjenta® ), saxagliptin (Onglyza® ), sitagliptin (Januvia® ).o Amylin agonist: pramlintide (Symlin® ).o Sodium-glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (Jardiance® ), canagliflozin (Invokana® ), dapagliflozin (Farxiga® ), ertugliflozin (Steglatro® ). o Miscellaneous agents.