Diabetes and Antidiabetic Drugs

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.

Keywords: Diabetes mellitus (DM), Antidiabetic drugs, Insulin, Biguanide, Insulin receptor (IR), Metformin, Sulfonylureas, Structure-activity relationship, SAE and drug-receptor.