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.
