Most pharmaceutical drugs sold today have their origin from biochemistry laboratory. Drug discovery started with biochemical pathway in human metabolism. The enzymatic activity, rate limiting steps in pathway was studied, characterized and purified from animal tissues. This kind of biochemical study helped pharmaceutical company to produce some of the effective drugs for variety of disease. It takes up to 15 years to develop one new drug from early stage of discovery till clinical study and to the patients. Many drugs coming to the market in 2013 actually were discovered in 1990’s. An average cost to research and development of each drug is about $800 million to $1 billion which includes failure too. There are some facts which can’t be imagined in Research and development with question like why so many products don't make it and why such long duration of time. It takes best scientific mind, highly sophisticated technology, project management persistence and somewhat luck to bring relief for millions of patients.

The advanced molecular and gene cloning technology has revolutionized drug discovery. Cloning methodology is used to produce targets that are difficult and dangerous to isolated naturally like HIV, virus their proteases, lethal cultures and pathogens. Cross hybridization of cloned sequence is very fast and effective method to recognize a specific target. New technology like X Ray Crystallography and powerful computer modeling chemists can "see" the target in 3D for designing and synthesizing new compound quickly.

Diabetes Mellitus is a chronic metabolic disorder characterized by Hyperglycemia caused by defective insulin secretion, resistance to insulin action or both. An alteration of lipid and protein metabolism also causes defect in action or secretion of insulin. There are two types of diabetes Type 1 which is immune mediated and Type 2 diabetes which is complex pathophysiology which combines insulin resistance, ß cell failure and hereditary factors. Diabetes is also related with gestational hormonal condition, genetic, some endocrinopathies, infection or drugs. Patients with diabetes have increased over 80 years; it is a major cause of morbidity and mortality in the world irrespective to age, gender and race or area.

Insulin in human body is produced by cells in pancreas called ß cells that control glucose level in blood. High level of glucose is detected in blood then a message is sent to pancreas, in response to it the ß cell are released to liver from pancreas. The insulin has an effect on number of cells like Muscle cells, Red Blood Cell and Fat cells. These cells absorb glucose out of blood brings back the normal level of glucose in blood stream.

Type 1 Diabetes Mellitus

Normal blood glucose level ranges between 70 mg/dl and 100 mg/dl. (Milligram of glucose present in 100 milliliters of blood). A blood glucose level below 70 mg/dl indicates "hypoglycemia" (low blood sugar) and glucose higher than 100 mg/dl "hyperglycemia" (high blood sugar). Normally after 2-3 hours after food glucose level is checked if it’s less than 140 mg/dl and over 200 mg/dl the patient is diagnosed with diabetes. As stated earlier, insulin is the essential glucose lowering therapy for the treatment of patients with Type 1 diabetes. Therefore, all experimental treatments for type 1 diabetes that are not insulin analogues or other insulin receptor ligands should be studied and understood well. Preclinical data or knowledge of a particular mechanism of action indicate that an investigational product has the potential to cause or worsen hypoglycemia, either by binding to insulin receptors or by affecting other aspects of glucose absorption and metabolism. However, pharmacodynamic interactions with insulin, as well as the need to adjust insulin doses to prevent hypoglycemia, this could pose significant challenges for study design, interpretation, and inference of the new drug’s efficacy.

Type 2 Diabetes Mellitus

Type 2 diabetes is a complex and heterogonous disorder affecting 100 million people worldwide. Type 2 is called non insulin dependent diabetes unlike people with Type 1, the people of type 2 produce insulin but their pancreas don’t make enough insulin or body is unable to use it. So it’s called insulin resistant, when glucose build up in blood the body cell is unable to function and process it. Efficacy and safety of new products for the treatment of type 2 diabetes can be evaluated in placebo-controlled monotherapy trials, placebo-controlled add-on therapy trials, and active-controlled trials. Given the progressive nature of type 2 diabetes and the requirement for multiple drug therapy, the clinical development program should involve evaluation of the investigational drug as monotherapy and in combination with many other approved antidiabetic drugs. In the past, oral agents (i.e., sulfonylurea’s) to treat type 2 diabetes were approved largely on the basis of placebo-controlled trials with no underlying pharmacological therapy, in which all randomized subjects received only counseling for appropriate diet and an exercise program in addition to the product being tested. As medical care for diabetes has evolved, it may now be difficult to find patients who are appropriate candidates for purely placebo-controlled trials because a large proportion of those diagnosed with diabetes are receiving early pharmacological treatment. Many verities of medication have been discovered and produced which showed satisfactory results. Some of the widely used medications are: -

Biguanides (Metformin)

Some of the brand names of Biguanides are Apo- Metformin, Diabex, Diabex XR, Diaformin XR, Genepharm Metformin and Glucobete. These medicines help in lowering blood glucose by reducing the amount of stored glucose released by liver, slowly absorb glucose from gut, helps body to become more sensitive to insulin so that insulin released from the body could work better. Side effects nausea, diarrhea and metallic taste in mouth, for reducing side effect it should be taken after meal I lower dose as prescribed by doctor. Metformin showed reduced death rate in Type 1 diabetes patients. Metformin is prescribed as 1st diabetes tablet for people suffering from Type 2 diabetes with overweight. Not recommended to patients with severe liver, kidney and heart diseases.

Sulphonylureas

Chemical names Gliclazide, Libenclamide, Glipizide and Glymepiride. Some of the brand names are Apo-gliclazide MR, Diamicron, Genrx gliclazide, Glyade, Mellihexal, Nidem, Daonil, Glimel. They lower blood glucose level by stimulating pancreas to release more insulin. Medication shows it lowers the risk of Hypoglycaemia when taken before meal. Not recommended to pregnant women and breast feeding patients.

Thiazolidinediones (Glitazones)

Chemically named as Rasiglitazone, Pioglitazone, some brended names are Actos, Apotex Pioglitazone, Pizaccord and Vexazone. These medication help in reducing blood glucose level by increasing effect of own insulin on muscle and fat cell and improve insulin resistance. The working process of this is slow and takes 2 months to show full effect. Works well with some of the other diabetes drugs too. Hypoglycaemia is not seen, chances of over weight gain is possible.

Alpha Glycosidase Inhibitor

Chemically named as Acarbose, branded Glucobay. They slow down the digestion and absorption of dietary carbohydrates in gut. Do not cause hypoglycemia. Works well with other diabetes medications including insulin. Some of the side effects are bloating, diarrhea. Dose is initially is low as time passes the dose in increased.

Incretin Mimetics

Chemical name Exenatide branded Byetta. These are injected medications. They mimic the effects of the body’s own ‘incretin hormones’ which help to manage blood glucose levels after meals. It stimulates pancreas to release more insulin in response to intake of carbohydrates, reduces amount of glucagon from pancreas after meals. Slowdowns food passage so that gut absorbs slowly and steadily. Injected twice a day under skin, abdomen or upper arm. Side effects nausea, vomiting, diarrhea, allergy in some cases.

Nesina (alogliptin) is a new DPP-4 inhibitor designed to slow the inactivation of incretin hormones GLP-1 and GIP, resulting in more active incretins enabling the pancreas to secrete insulin and better managing blood glucose levels.

Invokana (Canagliflozin ) is the first sodium-glucose co-transporter 2 (SGLT2) inhibitor approved for patients with type 2 diabetes. SGLT2 inhibitors work in conjunction with the kidneys and the natural urination process to remove excess blood glucose from the body.

Duetact (pioglitazone/glimepiride) combines two previously approved type 2 diabetes medicines with complementary actions in a single tablet. One medicine targets insulin resistance while the other increases the amount of insulin produced by the pancreas. Farxiga (dapagli? ozin) is a new SGLT2 inhibitor approved to improve glycemic control in adults with type 2 diabetes.

We are in the era of technological advancements in diabetes care. Advances in diabetes technology will continue to improve patient care and its delivery, and may one day lead to fully automated treatment systems for people with diabetes mellitus


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