Anti diabetic agents

The number of people with diabetes mellitus, Type 1 (insulin-dependent) and Type 2 (non-insulin dependent) combined, has increased globally in the past few decades, and diabetes mellitus remains one of the major causes of death. Estimated 420–530 million of the world population are diabetic, of whom 90% are type 2 diabetics. Although it is confirmed that genetic predisposition partly determines individual susceptibility to T2DM, but several other factors (imbalanced diet, sedentary lifestyle, many forms of stress, lack of physical activity) are considered key drivers of this ongoing epidemic. Literature shows exposure to drugs, chemicals, and early developmental factors, such as intrauterine exposures can also contribute to the susceptibility to T2DM later in life. Diabetics often develop serious health consequences, such as retinopathy, neuropathy, nephropathy, cardiomyopathy, high blood pressure etc. To treat ∼37 million diabetics in the United States, it costs >$170 each year. The vast majority of the current medications are aimed at maintaining HbA1c levels via suppressing hepatic glucose production, activating β-cells to release insulin, increasing tissue sensitivity to insulin, increasing peripheral glucose utilization, and decreasing glucose absorption in the gut. Although most agents are designed to treat hyperglycemia or indirectly lower HbA1c, their long-term effects on the pathophysiology of β-cell function has not been well documented. The major classes of agents that are available include biguanides, sulfonylureas, meglitinides, dipeptidyl-peptidase-4 inhibitors (aka DPP-4i), Glucagon like peptide-1 (GLP-1) agonists, Sodium Glucose Cotransporter-2 inhibitors (aka SGLT-2i), alpha-glucosidase inhibitors, thiazolidinediones, and many forms of insulin. All these agents show toxicity and adverse reactions at some point, short-term or long-term. Many agents show drug interactions, and a few are dependent on patient pharmacogenetics. This review is focused on mechanisms of actions of all these classes and their possible adverse effects.