Metformin is still the most widely used oral drug in diabetes management. It has got a wide range of indication ranging from prediabetes. It can also be used along with insulin, sulphonylurea, DPP4 inhibitor etc. Major contra indications are creatinine more than 1.5mg/dl in males and 1.4mg/dl in females. In hospitalized patients with severe organ failure (sepsis,hypoxemia) etc,.metformin should be avoided

Research from the Johns Hopkins Children's Centre reveals that the drug most commonly used in Type 2 diabetics who don't need insulin works on a much more basic level than once thought, treating persistently elevated blood sugar -- the hallmark of Type 2 diabetes -- by regulating the genes that control its production. Investigators say they have zeroed in on a specific segment of a protein called CBP

(CREB-binding Protein) made by the genetic switches involved in overproduction of glucose by the liver that could present new targets for drug therapy of the disease. Insulin resistance in Diabetes patients is caused by a glitch in the communication between liver and pancreas.

Metformin, introduced as frontline therapy for uncomplicated Type 2 diabetes in the 1950s, up until now was believed to work by making the liver more sensitive to insulin. The Hopkins study shows, however, that metformin bypasses the stumbling block in communication and works directly in the liver cells.” Rather than an interpreter of insulin-liver communication, metformin takes over as the messenger itself…. Metformin actually mimics the action of CBP, the critical signalling protein involved in the communication between the liver and the pancreas." Senior investigator, Fred Wondisford, M.D., who heads the metabolism division at Hopkins Children's, concluded.

The researchers tested their hypothesis by making rats insulin insensitive through high fat diet and then giving metformin The scientists were successful in reducing insulin insensitivity using metformin, but when they introduced defective CBP and on using metformin again, the mice stopped responding to the drug. Researchers further were able to determine that metformin worked on one particular section of CBP by studying the drug's effects in mice with normal CBP and in mice missing this section of their CBP. The mice with normal CBP responded to metformin with a drop in their fasting blood glucose -- much like diabetes patients do -- while the mice missing that section in their CBP had no decrease in their blood sugar.

Investigators have discovered a biomarker as well that can predict how well a person will respond to treatment with metformin and help doctors determine the optimal therapeutic dose, which can vary widely from person to person. “We have found an easily obtainable biomarker with great predictive power that can tell us whether and how well an individual will respond to treatment and help us determine the best dose right away instead of trying to do it by trial and error," Wondisford says. Researchers caution that, while promising, their findings must be first replicated in humans.