NEED FOR NEW HYPOGLYCEMIC AGENTS: AN OVERVIEW

Diabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. Insulin deficiency in turn leads to chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism. It is the most common endocrine disorder and by the year 2010, it is estimated that more than 200 million people worldwide will have DM and 300 million will subsequently have the disease by 2025. As the disease progresses tissue or vascular damage ensues leading to severe diabetic complications such as retinopathy, neuropathy, nephropathy, cardiovascular complications and ulceration. Thus, diabetes covers a wide range of heterogeneous diseases. Diabetes mellitus may be categorized into several types but the two major types are type 1 and type 2. Drugs are used primarily to save life and alleviate symptoms. Secondary aims are to prevent long-term diabetic complications and, by eliminating various risk factors, to increase longevity. Insulin replacement therapy is the mainstay for patients with type 1 DM while diet and lifestyle modifications are considered the cornerstone for the treatment and management of type 2 DM. Insulin is also important in type 2 DM when blood glucose levels cannot be controlled by diet, weight loss, exercise and oral medications. Oral hypoglycemic agents are also useful in the treatment of type 2 DM. Oral hypoglycemic agents include sulphonylureas, biguanides, meglitinide, DPP-IV inhibitors, α- glucosidase inhibitors, thiazolidenediones, bile acid sequestrant, D2 dopamine receptor agonist, GLP-1 receptor agonist, amylin analogues. The main objective of these drugs is to correct the underlying metabolic disorder, such as insulin resistance and inadequate insulin secretion. They should be prescribed in combination with an appropriate diet and lifestyle changes. Diet and lifestyle strategies are to reduce weight, improve glycemic control and reduce the risk of cardiovascular complications, which account for 70% to 80% of deaths among those with diabetes. Diabetes is best controlled either by diet alone and exercise (non-pharmacological), or diet with herbal or oral hypoglycemic agents or insulin (pharmacological). The main side effects are weight gain and hypoglycemia with sulphonylureas, gastrointestinal (GI) disturbances with metformin, weight gain, GI disturbances and liver injury with thiazolidinediones, GI disturbances, weight gain and hypersensitivity reactions with meglitinides and flatulence, diarrhoea and abdominal bloating with alpha-glucosidase inhibitors. In this article, different types of diabetes, current treatment and their adverse effects which lead to development of new hypoglycemic agents have been studied.