Pioglitazone cuts risk of progression to diabetes.SAN FRANCISCO- people with impaired glucose tolerance Impaired Glucose Tolerance (IGT) is a pre-diabetic state of dysglycemia, that is associated with insulin resistance and increased risk of cardiovascular pathology. IGT may precede type 2 diabetes mellitus by many years. IGT is also a risk factor for mortality. were 81% less likely to develop type 2 diabetes type 2 diabetes
See diabetes mellitus. over a 3-year period if treated with pioglitazone, according to a prospective, randomized ran·dom·ize
tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es
To make random in arrangement, especially in order to control the variables in an experiment. , double-blind, placebocontrolled study of 602 patients.
One new case of diabetes could be avoided per year for every 3.5 patients treated with pioglitazone for impaired glucose tolerance, Dr. Ralph A. DeFron zo said at the annual scientific sessions of the American Diabetes Association The American Diabetes Association, or the ADA, is an American health organization providing diabetes research, information and advocacy. Founded in 1940, the American Diabetes Association conducts programs in all 50 states and the District of Columbia, reaching hundreds of . His report caused a wave of excited murmurs and some uncharacteristic cheers from the packed audience.
The 303 patients on the thiazolidinedione pioglitazone (Actos) also significantly improved on measures of insulin resistance Insulin Resistance Definition
Insulin resistance is not a disease as such but rather a state or condition in which a person's body tissues have a lowered level of response to insulin, a hormone secreted by the pancreas that helps to regulate the level and [beta]-cell function, while there were no significant changes in the 299 patients on placebo, Dr. DeFronzo, professor of medicine and division chief at the University of Texas Health Science Center, San Antonio, said in an interview.
In the pioglitazone group, 1.5% of patients per year developed diabetes, compared with 6.8% per year on placebo. Impaired glucose tolerance converted back to normal glucose tolerance in 42% of the pioglitazone group by the end of the study, compared with 28% on placebo.
"It's a very impressive study. Those are numbers you don't see very often," Dr. Paul Jellinger commented in a phone interview.
The findings are likely to increase the off-label treatment of prediabetes prediabetes /pre·di·a·be·tes/ (pre-di?ah-bet´ez) a state of latent impairment of carbohydrate metabolism in which the criteria for diabetes mellitus are not all satisfied.
n. with thiazolidinediones (TZDs) as monotherapy or in combination with metformin metformin /met·for·min/ (met-for´min) an antihyperglycemic agent that potentiates the action of insulin, used in the treatment of type 2 diabetes mellitus.
n. , according to Dr. Jellinger, professor of medicine on the voluntary faculty at the University of Miami This article is about the university in Coral Gables, Florida. For the university in Oxford, Ohio, see Miami University.
The University of Miami (also known as Miami of Florida, UM, or just The U and a past president of both the American College of Endocrinology and the American Association of Clinical Endocrinologists.
There are no medications approved for the treatment of prediabetes to prevent progression to diabetes. Metformin probably is the most common off-label treatment used for this purpose, Dr. Jellinger said, because a previous study showed similar--though not as striking--bene fits. Adding metformin may modulate some of the weight gain associated with TZDs, he noted.
In Dr. DeFronzo's trial, called the Actos Now for Prevention of Diabetes (ACT NOW) study, patients started with an average body mass index of 34 kg/[m.sup.2] and gained a mean of 3.5 kg (about 8 pounds) in the pioglitazone group and 0.7 kg (less than 2 pounds) in the placebo group over a mean 2.6-year follow-up.
Patients had a mean age of 52 years and were recruited in eight medical centers over a 2-year period, then followed for at least 2 more years or until a diabetes diagnosis. All had 2-hour glucose values of 140-199 mg/dL on oral glucose concentration of 95-125 mg/dL, and one or more other high-risk characteristics (at least one component of the metabolic syndrome metabolic syndrome
See syndrome X.
A group of risk factors for heart disease, diabetes, and stroke. , a family history of type 2 diabetes, a history of gestational diabetes Gestational Diabetes Definition
Gestational diabetes is a condition that occurs during pregnancy. Like other forms of diabetes, gestational diabetes involves a defect in the way the body processes and uses sugars (glucose) in the diet. , the presence of polycystic ovary syndrome Polycystic Ovary Syndrome Definition
Polycystic ovary syndrome (PCOS) is a condition characterized by the accumulation of numerous cysts (fluid-filled sacs) on the ovaries associated with high male hormone levels, chronic anovulation (absent ovulation), , or minority ethnic background).
A combination of impaired glucose tolerance and impaired fasting glucose fasting glucose Fasting blood sugar, fasting plasma glucose Endocrinology Glucose obtained from a Pt who has had nothing–except water by mouth for 8+ hrs; FG is used in evaluating Pts for possible DM Ref range 65-115 mg/dL non-diabetic; 110-140 mg/dL, was present in 68% of patients, and the rest had isolated impaired glucose tolerance. Compared with 102 healthy matched con trols, patients in the study showed a 48% reduction in insulin sensitivity insulin sensitivity The systemic responsiveness to glucose, which can be measured by 1. The insulin sensitivity index–measures the ability of endogenous insulin to ↓ glucose in extracellular fluids by inhibiting glucose release from the liver and and a 78% decrease in the insulin secretion / insulin resistance index.
Patients were randomized to treatment with placebo or 30 mg/day pioglitazone. If the drug was tolerated after 1 month, the dose could be increased up to 45 mg/day. "What was quite surprising was how quickly pioglitazone dropped the fasting glucose," Dr. DeFronzo said.
"Within the first 3 months of initiating pioglitazone, there was a defined decrease in glucose" separating the two groups that was maintained to the end, he said. The study had 90% power to detect at least a 50% reduction in progression to diabetes in the treatment group vs. placebo.
Future long-term research should examine whether treating prediabetes with TZDs or metformin delays or actually prevents progression to diabetes, and whether these drugs reduce cardiovascular events in these patients, Dr. Jellinger suggested.
Approximately 21 million people in the United States have impaired glucose tolerance, which puts them at risk for diabetes and for cardiovascular disease, Dr. DeFronzo said. From 3% to 13% of people with impaired glucose tolerance go on to develop diabetes.
Dr. Jellinger is on the speakers bureau of Takeda Pharmaceutical Co., which makes pioglitazone, as well as the speakers' bureaus for Merck, Novo Nordisk, Eli Lilly & Co., Amylin Pharmaceutical, and Glaxo SmithKline.
Dr. DeFronzo is an adviser and speaker for Takeda, which funded the study. He also is a consultant, adviser, or speaker for, or has received research support from Bristol-Myers Squibb Co., Amylin Pharmaceuticals Inc., Eli Lilly & Co., Novartis, Pfizer Inc., Roche Duagnistucs, AstraZenca Pharameceuticals LP,Johnson& Johndon, and Isis Pharamaceuticals Inc.
BY SHERRY BOSCHERT
San Francisco Bureau