Several new drugs for NIDDM are in clinical trials or on the market. Earlier this year the DDA approved a new oral anti-diabetic agent (metformin), and recently a FDA committee recommended the approval of another anti-diabetes agent (acarbose). One of the most interesting new drugs being tested for NIDDM is troglitazone, a member of the thiazolidinedione class of anti-diabetic agents. The thiazolidinedione, which include ciglitazone and pioglitazone as well as troglitazone, have a beneficial effect on insulin resistance and may actually be useful for preventing NIDDM. These agents increase glucose consumption and reduce its production by potentiation the action of insulin in liver, skeletal muscle, and adipose tissue.

The thiazolidinedione have been shown to reduce elevated plasma glucose, triglycerides, and insulin concentrations in animals with hyperinsulinemia and to improve both fasting and postprandial hyperglycemia and hyperinsulinemia in patients with NIDDM. This reduction in hyperglycemia is associated with near normalization of the rates of hepatic glucose production and a 40-60% increase in insulins mediated glucose disposal. In two studies of troglitazone inpatients with NIDDM, the drug decreased fasting and postprandial glucose and insulin concentrations, improved glucose tolerance, decreased hepatic glucose output, and increased insulin sensitivity. There was also a decrease in plasma triglyceride concentrations and an increase in plasma high-density lipoprotein cholesterol concentrations.

Recently Nolan et al. reported the results of a placebo-controlled trial of troglitazone in 18 obese patients with insulin resistance. A 12-week course of the drug increased insulin sensitivity, improved glucose tolerance, and reduced hyperinsulinemia. The drug also produced a small but significant reduction in both systolic and diastolic blood pressure. The drug was well tolerated; no subjective side effects were noted, nor were there any persistent abnormalities in laboratory variables.

Obesity, a sedentary lifestyle, and aging all contribute to NIDDM, wrote the investigators, "but insulin resistance is probably a primary inherited feature on most patients with NIDDM." Insulin resistance and hyperinsulinemia are present many years before the development of glucose intolerance. As beta cell function declines, glucose intolerance develops, followed eventually by hyperglycemia and diabetes. "The fact that troglitazone can improve insulin resistance, lower plasma insulin concentrations, and normalize glucose tolerance in subjects with impaired glucose tolerance could have implications for the prevention of NIDDM," concluded the investigators.

In an editorial comment on the Nolan report, Harry Keen wrote that correcting insulin resistance that is, the pharmacological treatment of the metabolic syndrome X could prevent the development of an important group of disease states. He noted, however, "Medical moralists will despair that pharmacological inventiveness may now allow people to become even fatter and lazier without having to face their metabolic nemesis."