Showing papers by "Silvio E. Inzucchi published in 2003"
TL;DR: The role of metformin in the treatment of patients with type 2 diabetes and its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease are reviewed.
Abstract: Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent. Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder. While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option. We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone. We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease.
321 citations
TL;DR: The use of metformin and thiazolidinediones is common and has increased rapidly in Medicare beneficiaries with diabetes and heart failure in direct contrast with explicit warnings against this practice by the Food and Drug Administration.
Abstract: ContextAccording to package inserts, metformin is contraindicated in diabetic
patients receiving drug treatment for heart failure therapy, and thiazolidinediones
are not recommended in diabetic patients with symptoms of advanced heart failure.
Little is known about patterns of use of these antihyperglycemic drugs in
diabetic patients with heart failure.ObjectiveTo determine the proportions of patients hospitalized with heart failure
and concomitant diabetes treated with metformin or thiazolidinediones.DesignSerial cross-sectional measurements using data from retrospective medical
record abstraction.SettingNongovernmental acute care hospitals in the United States.PatientsTwo nationally representative samples of Medicare beneficiaries hospitalized
with the primary diagnosis of heart failure and concomitant diabetes between
April 1998 and March 1999 and between July 2000 and June 2001.Main Outcome MeasuresThe prescription of either metformin or a thiazolidinedione at hospital
discharge.ResultsIn the 1998-1999 sample (n = 12 505), 7.1% of patients were discharged
with a prescription for metformin, 7.2% with a prescription for a thiazolidinedione,
and 13.5% with a prescription for either drug. In the 2000-2001 sample (n
= 13 158), metformin use increased to 11.2%, thiazolidinedione use to
16.1%, and use of either drug to 24.4% (P<.001
for all comparisons). Similar increases were seen among patients of all age
groups, all races, and both sexes.ConclusionsThe use of metformin and thiazolidinediones is common and has increased
rapidly in Medicare beneficiaries with diabetes and heart failure in direct
contrast with explicit warnings against this practice by the Food and Drug
Administration. Further studies to establish the safety and effectiveness
of this practice are needed to ensure optimal care of patients with diabetes
and heart failure.
127 citations
TL;DR: Impaired insulin sensitivity is highly prevalent among nondiabetic patients with a recent TIA or nondisabling ischemic stroke, and this finding has important therapeutic implications if treatment to improve insulinensitivity is shown to reduce risk for subsequent stroke and heart disease.
Abstract: Objectives: To determine the prevalence of impaired insulin sensitivity among nondiabetic patients with a recent TIA or nondisabling ischemic stroke. Methods: Eligible subjects were nondiabetic men and women over age 45 years who were hospitalized with a TIA or ischemic stroke. To measure insulin sensitivity, subjects underwent an oral glucose tolerance test between 2 and 6 months after their event. Impaired insulin sensitivity was defined by a value of ≤2.5 on the Composite Insulin Sensitivity Index derived from insulin and glucose values during the test. Results: Between July 2000 and June 2001, we identified 177 eligible patients, among whom 105 declined to participate and 72 enrolled. The median age of participants was 71 years and 46 (64%) were men. The baseline event was stroke for 57 subjects (79%). A history of myocardial infarction (MI) was reported by 14 subjects (19%), and 16 (22%) were obese (body mass index > 30). Fasting glucose was normal ( 1). Conclusion: Impaired insulin sensitivity is highly prevalent among nondiabetic patients with a recent TIA or nondisabling ischemic stroke. This finding has important therapeutic implications if treatment to improve insulin sensitivity is shown to reduce risk for subsequent stroke and heart disease.
101 citations
TL;DR: Pioglitazone is effective for improving insulin sensitivity among patients with recent TIA or stroke and impaired insulin sensitivity.
Abstract: Background and Purpose— The aim of this study was to determine the effectiveness of pioglitazone compared with placebo for improving insulin sensitivity among nondiabetic patients with a recent transient ischemic attack (TIA) or nondisabling ischemic stroke and impaired insulin sensitivity. Methods— Eligible subjects were men and women >45 years of age who had no history of diabetes, fasting glucose <7.0 mmol/L, and impaired insulin sensitivity according to an index calculated from insulin and glucose blood levels obtained during an oral glucose tolerance test. Eligible subjects were randomized to pioglitazone 45 mg/d or placebo. After 3 months of therapy, the glucose tolerance test was repeated. Results— Between July 2000 and June 2001, we performed oral glucose tolerance tests on 75 patients with no history of diabetes, among whom 36 (50%) were found to have impaired insulin sensitivity and fasting glucose <7.0 mmol/L. Among these 36, 20 consented to the trial. Patients assigned to pioglitazone (n=10) a...
73 citations
TL;DR: This article focuses on several important endocrine emergencies, including diabetic hyperglycemic states, adrenal insufficiency, myxedema coma, thyroid storm, and pituitary apoplexy.
58 citations
TL;DR: The largest prospective trial of type 2 diabetes showed that glucose control decreased the microvascular complications of diabetes, and the trial demonstrated that elevated LDL cholesterol and decreased HDL cholesterol levels were among the strongest predictors of fatal and nonfatal myocardial complications.
Abstract: “… with fat diabetes begins. From fat diabetics die, formerly of coma and recently of … arteriosclerosis.” Three-quarters of a century ago, Dr. Elliot Joslin succinctly summarized two of the lethal consequences of diabetes before (ketoacidosis) and after (cardiovascular disease [CVD]) the discovery of insulin (1). As we progressively refine our ability to normalize blood glucose with increasingly complex regimens of new oral and injectable agents, the excess cardiovascular mortality from diabetes remains unabated (2). With diabetes increasing worldwide due to decreased physical activity and an aging and more obese population, and with type 2 diabetes being diagnosed at earlier ages (3,4), without effective preventive strategies the associated atherosclerotic complications are likely to soon reach unmanageable proportions. This prediction lies in sharp contrast to a decrease in cardiovascular mortality in the general population that has been recently reported (5).
The precise link between CVD and diabetes is not completely understood, but it is clearly multifactoral, involving the deleterious effects of hyperglycemia itself, resulting in endothelial dysfunction, hypercoagulability, increased oxidative stress, and protein glycosylation. In the setting of type 2 diabetes, there are the additional contributions of obesity, hypertension, dyslipidemia, insulin resistance, and further abnormalities in fibrinolysis and endothelial function (6). With the onset of diabetic nephropathy the risk of macrovascular disease is compounded. The exact role of each of these derangements is complicated by their complex interrelationships. In the midst of such a large number and variety of risk factors, however, dyslipidemia remains a key determinant of CVD. While the U.K. Prospective Diabetes Study (UKPDS), the largest prospective trial of type 2 diabetes, showed that glucose control decreased the microvascular complications of diabetes, the trial demonstrated that elevated LDL cholesterol (LDL-C) and decreased HDL cholesterol (HDL-C) levels were among the strongest predictors of fatal and nonfatal myocardial …
18 citations
8 citations
2 citations
TL;DR: Lifestyle intervention and metformin therapy both reduced the incidence of diabetes in patients at high risk, with the former being more effective than the latter.
Abstract: Diabetes Prevention Program Research Group: Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.
N Engl J Med 346:393–403, 2002
[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]
Objective . To determine whether improvement in risk factors for type 2 diabetes (mild hyperglycemia, overweight, sedentary lifestyle) with lifestyle change or metformin (Glucophage) can prevent or delay diabetes.
Design. A multicenter (27 sites), randomized, clinical trial.
Subjects and methods. A total of 3,324 adults with impaired glucose tolerance (IGT) and elevated fasting plasma glucose (FPG) (95–125 mg/dl) were randomized to receive placebo, metformin (850 mg twice daily), or intensive lifestyle change (weight loss ≥7% body weight and moderate physical activity ≥150 minutes per week), and followed for 3 years.
Results. At baseline, the mean age was 50.6 years, body mass index (BMI) was 34.0 kg/m2, FPG was 106.5 mg/dl, and 2-hour plasma glucose was 164.6 mg/dl. Non-white ethnic patients comprised 45% of the study population. The incidence of diabetes during an average follow-up of 2.8 years was 11.0, 7.8, and 4.8 cases per 100 person-years in the three assignment groups, respectively. The incidence of diabetes was reduced by 58% in the lifestyle group and by 31% in the metformin group.
Conclusion. Lifestyle intervention and metformin therapy both reduced the incidence of diabetes in patients at high risk, with the former being more effective than the latter.
The Diabetes Prevention Program (DPP) assessed the long-held notion that diet and exercise could prevent or delay type 2 diabetes. Using different study designs in smaller cohorts, the effectiveness of …
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