Diabetes mellitus (DM) is a progressive disease characterized by insulin deficiency and insulin resistance or both. The fasting and post-prandial blood glucose is elevated, exposing the patient to acute and chronic complications (micro- and macro-vascular) leading to blindness, kidney failure, heart disease, stroke and amputations. Improving glycemic control has been demonstrated to lower the risk of these complications. Owing to the progressive nature of the disease, an evolving treatment strategy is necessary to maintain glycemic control. Varieties of new pharmacologic interventions are developed in past 5 years to treat people with diabetes. Several studies have been carried out covering different aspects of pharmacological interventions (newer and old drugs) along with the effects of weight loss, diet and exercise. Two categories of drugs have been used for the treatment of Diabetes Mellitus: the insulin and oral agents. Insulin analogues are molecules that differ from human insulin in amino acid sequence but bind to the insulin receptors and act similarly in function. This article provides an update of pharmacologic interventions for diabetes with practical overview of the new drug options, new insulin analogues, pharmacology, clinical efficacy, safety, dosing, cost, with specific examples of each and their background and side effects used to achieve tight glucose control. These agents have distinct characteristics that help in their selection for the treatment of type 1 and type 2 diabetes.