Type 2 Diabetes Treatment with Oral Antidiabetic Drugs

New Orleans—With an increasing number of people with prediabetes and type 2 diabetes, healthcare professionals are spending countless hours and dollars trying to figure out ways to prevent and treat the disease. At the ASHP meeting, 2 pharmacists explained risk factors and detrimental effects associated with the disease as well as therapeutic options in an education session titled Oral Antidiabetic Drugs for the Prevention of Type 2 Diabetes. Craig I. Coleman, PharmD, associate professor of pharmacy practice at the University of Connecticut’s School of Pharmacy, said the age-adjusted percentage of adults in the United States with type 2 diabetes has risen significantly from 1994 through 2009. In 2009, nearly every state had >7.5% of adults with diabetes, according to statistics from the Centers for Disease Control and Prevention. During that period, there were similar trends in obesity, which Dr. Coleman defined as a body mass index (BMI) ≥30 kg/m2. He suggested there may be a “very strong tie” between the increasing incidence of obesity and diabetes. As of 2010, 8.3% of adults in the United States (approximately 25.8 million people) had type 2 diabetes, and more than two-thirds of patients developed the disease after the age of 45 years, according to Dr. Coleman. Of the 1.9 million new cases of type 2 diabetes diagnosed in 2009, 1.052 million occurred in people between 45 and 64 years of age, while 390,000 were in people ≥65 years of age and 465,000 were in those between 20 and 44 years of age. Dr. Coleman said risk factors associated with type 2 diabetes can be classified as nonmodifiable or modifiable. Nonmodifiable risk factors include age (≥40 years), a strong family history of type 2 diabetes, ethnicity (particularly nonwhites), and people with a history of gestational diabetes. He said that modifiable risk factors are those that can be fixed or altered and include previously identified glucose intolerance, BMI ≥25 kg/m2, habitual physical inactivity, elevated cholesterol, hypertension, and psychosocial stress and/or major depressive disorders. There are several complications associated with type 2 diabetes. The disease is the leading cause of kidney failure as well as new cases of blindness in adults between 20 and 74 years of age. In addition, approximately 64% to 70% of patients with type 2 diabetes have mild-to-severe nervous system damage. Furthermore, of the diabetes-related deaths in 2004 for people ≥65 years of age, 68% had heart disease and 16% had a stroke. Dr. Coleman also discussed prediabetes, which the American Diabetes Association (ADA) defines as blood glucose or hemoglobin A1c (HbA1c) levels higher than normal but not high enough to qualify as having diabetes. He said 35% of adults in the United States (79 million people) have prediabetes, and they are at an increased risk of developing type 2 diabetes, heart disease, or stroke. The ADA has published recommendations for screening patients with prediabetes, according to Dr. Coleman. Any person ≥45 years of age should be screened, but particularly those with BMI ≥25 kg/m2 or ≥23 kg/m2 for Asian-Americans. People <45 years of age with BMI ≥25 kg/m2 and additional risk factors for type 2 diabetes should also be screened. Dr. Coleman said they can be screened using fasting plasma glucose (FPG), the 2-hour oral glucose tolerance test (OGTT), or HbA1c level, and positive results should be confirmed at another visit. The ADA also recommends rescreening every 3 years. To diagnose prediabetes, Dr. Coleman said an abnormal FPG is between 100 and 125 mg/dL, an abnormal 2-hour OGTT is between 140 and 199 mg/dL, and an abnormal HbA1c level is between 5.7% and 6.4%. Olivia J. Phung, PharmD, assistant professor of pharmacy practice at Western University of Health Sciences’ College of Pharmacy in Pomona, California, followed with an overview of trials that led to the treatment guidelines for type 2 diabetes. Therapeutic options include lifestyle modifications such as diet and exercise as well as oral antidiabetic drugs. Of the 12 trials that implemented a change in diet, exercise, or both, the relative risk reduction of type 2 diabetes ranged from 16% to 71%, and 8 of the trials had a significant reduction (P<.05). Dr. Phung said a meta-analysis of trials showed that patients in the diet, exercise, or diet plus exercise groups had a significant reduction in type 2 diabetes development compared with a control group. Dr. Phung also discussed major trials of antidiabetic drugs such as metformin, acarbose, rosiglitazone, and pioglitazone. The studies included the DPP (Diabetes Prevention Program), STOP-NIDDM (Study to Prevent Non-Insulin Dependent Diabetes Mellitus), DREAM (Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medication), and ACT-NOW (Actos Now for Prevention of Diabetes). Dr. Phung conducted a systematic review of oral antidiabetic drugs used as monotherapies to prevent diabetes and trials that examined adults who were at risk of developing diabetes and had impaired fasting glucose, impaired glucose tolerance, or elevated BMI. For a trial to be included in the analysis, it had to have evaluated any of the oral antidiabetic drug classes, including biguanides, sulfonylureas, glinides, thiazolidinediones, and alpha-glucosidase inhibitors. The trials needed to compare the oral antidiabetic drug with placebo or another oral antidiabetic drug and had to have lasted ≥3 months. Patients were followed for a median of 2.7 years, with a range of 0.3 to 7 years. Dr. Phung found that thiazolidinediones, alpha-glucosidase inhibitors, and biguanides had a significant reduction in the risk of developing type 2 diabetes compared with placebo. There was no statistically significant difference between placebo and sulfonylureas or glinides. In 2011, the US Food and Drug Administration (FDA) issued recommendations for the restricted use of rosiglitazone and pioglitazone, which are both thiazolidinediones. After reports of an increased risk of cardiovascular events associated with rosiglitazone, the FDA said that the drug should only be used by patients who cannot control glucose levels with other medications. The FDA also warned that patients with active bladder cancer should not use pioglitazone, and those with a history of bladder cancer should be cautious before taking the medication. “In spite of all the efficacy, we cannot ignore the safety considerations with the use of [thiazolidinediones],” Dr. Phung said.