Once- and Twice-Daily Dosing With Rosiglitazone Improves Glycemic Control
in Patients With Type 2 Diabetes
Lawrence S. Phillips , MD ,
George Grunberger , MD ,
Elizabeth Miller , RN, BA ,
Rita ...Patwardhan , PHD ,
Elizabeth B. Rappaport , MD ,
Alan Salzman , MD, PHD and
the Rosiglitazone Clinical Trials Study Group
From the Division of Endocrinology (L.S.P.), Emory University School of
Medicine, Atlanta, Georgia; the Center for Molecular Medicine and Genetics and
the Department of Internal Medicine (G.G.), Wayne State University, Detroit,
Michigan; and Smithkline Beecham Pharmaceuticals (E.M., R.P., E.B.R., A.S.),
Collegeville, Pennsylvania.
Address correspondence and reprint requests to Lawrence S. Phillips, MD,
Division of Endocrinology, Emory University School of Medicine, 1639 Pierce
Dr., 1301 Woodruff Memorial Bldg., Atlanta, GA 30322. E-mail:
medlsp{at}emory.edu
.
Abstract
OBJECTIVE — To determine the efficacy of rosiglitazone compared
with placebo in reducing hyperglycemia.
RESEARCH DESIGN AND METHODS — After a 4-week placebo run-in
period, 959 patients were randomized to placebo or rosiglitazone (total daily
dose 4 or 8 mg) for 26 weeks. The primary measure of efficacy was change in
the HbA lc concentration.
RESULTS — Rosiglitazone produced dosage-dependent reductions in
HbA lc of 0.8, 0.9, 1.1, and 1.5% in the 4 mg o.d., 2 mg b.i.d., 8
mg o.d., and 4 mg b.i.d. groups, respectively, compared with placebo.
Clinically significant decreases from baseline in HbA lc were
observed in drug-naive patients at all rosiglitazone doses and in patients
previously treated with oral monotherapy at rosiglitazone 8 mg o.d. and 4 mg
b.i.d. Clinically significant decreases from baseline in HbA lc were
also observed with rosiglitazone 4 mg b.i.d. in patients previously treated
with combination oral therapy. Approximately 33% of drug-naive patients
treated with rosiglitazone achieved HbA lc ≤7% at study end. The
proportions of patients with at least one adverse event were comparable among
the rosiglitazone and placebo groups. There was no evidence of hepatotoxicity
in any treatment group. There were statistically significant increases in
weight and serum lipids in all rosiglitazone treatment groups compared with
placebo. For LDL and HDL cholesterol, the observed increase appeared to be
dose related.
CONCLUSIONS — Rosiglitazone at total daily doses of 4 and 8 mg
significantly improved glycemic control in patients with type 2 diabetes and
was well tolerated.
Footnotes
A.S. holds stock in SmithKline Beecham Pharmaceuticals, and E.B.R. holds
stock in SmithKline Beecham Pharmaceuticals and Johnson & Johnson
Corporation.
Abbreviations: ALT, alanine aminotransferase; HOMA, homeostasis
model assessment; PPAR-γ, peroxisome proliferator-activated
receptor-γ.
A table elsewhere in this issue shows conventional and
Système International (SI) units and
conversion factors for many substances.
Accepted October 12, 2000.
Received June 8, 2000.
by the American Diabetes Association,
Inc.
Purpose
To review efficacy and safety data of dipeptidyl peptidase-4 inhibitors used in treatment of patients with type 2 diabetes mellitus.
Methods
A search of MEDLINE®/PubMed®, a service of the ...National Library of Medicine of the National Institutes of Health as well as of the original publications of individual trials with dipeptidyl peptidase-4 inhibitors was carried out.
Results
Dipeptidyl peptidase-4 inhibitors are orally administered medications indicated for improved glycemic control in patients with type 2 diabetes. They inhibit activity of the enzyme dipeptidyl peptidase-4 responsible for inactivating nutrient-released incretin hormones (mainly glucagon-like peptide-1 and glucose-dependent insulinotropic peptide). As a result, the effect of the incretin hormones is enhanced, leading to improved β-cell function and inhibition of the glucagon secretion from the pancreatic islets. Patients can expect to see lowering of fasting and postprandial glucose levels (by 0.5–1 mmol/l and 2–3 mmol/l, respectively), leading to reduction of hemoglobin A1c by 0.5–0.9% (depending on the baseline hemoglobin A1c).
Conclusion
Dipeptidyl peptidase-4 inhibitors are generally well tolerated, with minimal risks of hypoglycemia or weight gain. Many postmarketing and surveillance studies are now conducted which focus on long-term safety and cardiovascular outcomes.
Background
V-Go is a wearable, patch-like, 24-h insulin delivery device that delivers both a continuous preset basal rate and on-demand bolus dosing. The aim of this study was to observe glycemic ...control, insulin dosing, and hypoglycemia risk in patients switched to V-Go in a real-world setting. The primary objective was to compare change in mean hemoglobin A1c (HbA1c) from baseline to the end of V-Go use.
Methods
This prospective, open-label, multicenter study recruited patients with type 2 diabetes (T2D) and suboptimal glycemic control (HbA1c ≥ 7%) across 28 centers. Efficacy analyses were conducted for all patients with a post-baseline HbA1c and results stratified based on prior antihyperglycemic medication therapies. Insulin dosing was at the discretion of the health care provider and the protocol did not mandate glycemic targets. Treatment satisfaction surveys were utilized to gain patient feedback on the use of V-Go.
Results
One hundred eighty-eight patients were enrolled in the study, among whom 140 patients had a valid post-baseline HbA1c and were included in the primary efficacy analysis. Use of V-Go resulted in a change of − 0.64%; (
P
= 0.003) in HbA1c from baseline, and in those prescribed insulin, the total daily dose of insulin was decreased by 12 units/day (
P
< 0.0001). Twenty-two patients (12%) reported hypoglycemic events (≤ 70 mg/dL), with an event rate of 1.51 events/patient/year.
Conclusion
In a T2D population with suboptimal HbA1c, initiating V-Go therapy in a real-world setting significantly improved glycemic control and led to significant insulin dose reductions.
ClinicalTrial.gov registry identifier: NCT01326598.
...one would predict that raising HDL levels in patients with Hp 2-2 DM may not have a favorable effect on HDL function. In a subset of AIM-HIGH participants with DM, niacin improved HDL antioxidant ...function in individuals with the Hp 1-1 genotype but worsened HDL antioxidant function in those with the Hp 2-2 genotype. ...assessment of HDL antioxidant function at study enrollment identified a very high percentage of individuals with dysfunctional pro-oxidative HDL and whose HDL antioxidant function further deteriorated with niacin therapy.
Several classes of antidiabetic agents have been introduced into the market place over the past dozen years. As our understanding of the underlying pathophysiology of type 2 diabetes has advanced, ...attempts have been made to address these defects specifically. This brief review focuses on our experience with two such pharmacological approaches: (i) a synthetic amylin analog addressing amylin deficiency; and (ii) a dopaminergic agonist, focused on enhancing the lowered dopaminergic tone in patients with type 2 diabetes. Importantly, the use of these agents is not associated with hypoglycemia or weight gain.
摘要
在过去的十几年里有几类降糖药物已经被推向了市场。随着我们对2型糖尿病潜在病理生理学的理解日益深入，我们已经在尝试研制特别针对这些缺陷的药物。这篇简要的综述关注于我们对以下两个药物的使用经验：（i）一种合成的胰淀素类似物，用来解决胰淀素缺乏的问题；以及（ii）一种多巴胺受体激动剂，用来增强2型糖尿病患者降低的多巴胺效应。重要的是，使用这些药物与低血糖或者体重增加都没有关系。
Abstract Background Niacin is an anti-dyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in non-diabetic statin-treated ...subjects with cardiovascular disease and at high risk for diabetes are less well known. Methods This was a pre-specified, intent-to-treat analysis of 3414 participants in the Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes trial randomized at 92 centers in the United States and Canada to ERN plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, non-diabetic subjects with 2 annual follow up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Results Compared to placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9±15.8 vs 4.3±10.3 mg/dl; p<0.001) and impaired fasting glucose (4.1±18.7 vs 1.4±14.9 p<0.02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336 cases (58.6%) versus placebo 135/325 cases (41.5%) p<0.001) over time, but no difference in diabetes development in the two treatment groups except in those with normal fasting glucose at baseline. Conclusions The addition of ERN to simvastatin/ezetemibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new onset diabetes. In addition ERN increased the risk of developing impaired fasting glucose which may have deleterious consequences over time and warrants further study.
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