exenatide and 2-4-thiazolidinedione

This review examines the use of exenatide twice daily in managing changes in markers of cardiovascular risk in patients with type 2 diabetes.. Type 2 diabetes is a progressive metabolic disorder, which results from defects in insulin secretion and/or insulin action leading to chronic hyperglycaemia and associated cardiovascular complications. Despite the use of diet, exercise, oral antihyperglycaemic agents and insulin, the progressive nature of the condition means that the levels of the preventive and treatment measures would have to be increased and/or new therapies have to be developed in order to address the long term impact of type 2 diabetes. The advent of exenatide, a glucagon-like peptide-1 receptor agonist provides a useful basis for managing type 2 diabetes and related cardiovascular complications without the side effects of regular diabetes therapies. However, exenatide twice daily is often used in combination with other therapies, although the mechanism of exenatide in managing diabetes and and associated cardiovascular risks and complications remain complex and still evolving.. A range of databases including EBSCOhost online research database were used to access articles based on PICO (Population, Interventions, Comparative Interventions, Outcomes) framework and Boolean operators.. Eleven randomised controlled studies which met the inclusion criteria were selected for this review. Nine of the eleven studies showed significant decrease in body weight among participants in the exenatide group compared with placebo or control group while the other two studies did not report statistically significant differences in body weight. In adition, all the studies showed statistically significant decrease in glycated haemoglobin (HbA1c) in the exenatide group compared to controls except in one study. In the present review, the seven studies, which looked at the effect of exenatide twice daily on lipid profile, did not find any significant difference between the exenatide group and the control group except for High density lipoprotein-cholesterol in two of the studies. However, statistically significant decrease was observed between exenatide group and controls with respect to blood pressure (systolic and/or diastolic) in these studies.. It would appear that exenatide is more effective in reducing body weight in patients with type 2 diabetes when used in combination with metformin than when used alone or in combination with thiazolidinedione. The findings of this review would suggest that exenatide twice daily may be useful in managing cardiovascular risks and complications by reducing body weight, HbA1c and blood pressure.

Topics: Biomarkers; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Peptides; Risk Factors; Thiazolidinediones; Venoms

The prevalence of obesity and diabetes is epidemic. Severe insulin resistance (defined as the need for > or = 200 units of insulin per day to achieve glycemic control) is commonly seen with obesity and can complicate diabetes management. The management of patients with diabetes who have severe insulin resistance is difficult, and at times frustrating, and requires a multifaceted approach. Weight loss is the best treatment option, which can be a challenging task for patients to achieve and maintain. Medications that decrease insulin needs like metformin, thiazolidinediones, or pramlintide may help, but some patients also need high doses of insulin. This article reviews these different treatment options and provides practical advice on weight loss, use of insulin sensitizers, and use of U-500 insulin.

Topics: Amyloid; Bariatric Surgery; Diabetes Mellitus; Diet, Reducing; Dipeptidyl-Peptidase IV Inhibitors; Exenatide; Exercise; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Islet Amyloid Polypeptide; Liraglutide; Metformin; Obesity; Peptides; Thiazolidinediones; Treatment Failure; Venoms; Weight Loss

To evaluate third-line thiazolidinedione (TZD) or glimepiride therapy in patients inadequately controlled on metformin + exenatide twice daily, and third-line exenatide twice daily in patients inadequately controlled on metformin + glimepiride.. In this randomized, open-label, multicentre trial, 144 patients with type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) >9% (75 mmol/mol) after 3 months' treatment or >7% (53 mmol/mol) at two consecutive visits 3 months apart, after 6 months' treatment] on metformin + exenatide twice daily were re-randomized to add-on TZD or glimepiride, and 166 patients inadequately controlled on metformin + glimepiride received add-on exenatide twice daily. Changes in HbA1c, body mass index (BMI), lipids, hypoglycaemia and vital signs were evaluated.. The median duration of triple therapy was ∼2 years. In patients inadequately controlled on metformin + exenatide twice daily, add-on TZD decreased HbA1c levels significantly better than add-on glimepiride: 130-week difference 0.48% [95% confidence interval (CI) 0.19-0.77] or 5.2 mmol/mol (95% CI 2.1-8.4; p = 0.001), but with significantly increased BMI and systolic blood pressure. The ratio of documented symptomatic (blood glucose ≤70 mg/dl [3.9 mmol/l]) hypoglycaemia rates for add-on glimepiride to add-on TZD was 8.48 (p < 0.0001). Add-on exenatide twice daily after metformin + glimepiride significantly reduced HbA1c levels: mean [standard deviation (s.d.)] change from baseline -0.35 (0.89)% [-3.8 (9.7) mmol/mol] and BMI: mean (s.d.) change from baseline -0.82 (1.9) kg/m(2) at 130 weeks, with a slightly increased rate of documented symptomatic hypoglycaemia from metformin + glimepiride (ratio 1.49).. TZD, but not glimepiride, was an effective and well tolerated third-line therapy in patients without glycaemic control after long-term therapy with metformin + exenatide twice daily. Exenatide twice daily was an effective and well tolerated third-line therapy in patients inadequately controlled on metformin + glimepiride.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Europe; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Lipids; Male; Metformin; Middle Aged; Peptides; Prospective Studies; Sulfonylurea Compounds; Thiazolidinediones; Treatment Failure; Venoms

Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported.. To compare the effects of exenatide versus placebo on glycemic control.. Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005.. 49 sites in Canada, Spain, and the United States.. 233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean (+/-SE) baseline glycated hemoglobin A1c level was 7.9% +/- 0.1%.. Subcutaneous abdominal injections of 10 microg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks.. The primary outcome was change from baseline in hemoglobin A1c level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events.. Exenatide treatment reduced hemoglobin A(1c) level (mean difference, -0.98% [95% CI, -1.21% to -0.74%]), serum fasting glucose level (mean difference, -1.69 mmol/L [-30.5 mg/dL] [CI, -2.22 to -1.17 mmol/L {-40.0 to -21.1 mg/dL}]), and body weight (mean difference, -1.51 kg [CI, -2.15 to -0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia.. Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study.. Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy. ClinicalTrials.gov registration number: NCT00099320. For more information on exenatide click here.

Topics: Adult; Aged; Blood Glucose; Blood Glucose Self-Monitoring; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Injections, Subcutaneous; Insulin-Secreting Cells; Male; Metformin; Middle Aged; Nausea; Peptides; Thiazolidinediones; Venoms; Vomiting; Weight Loss

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Exenatide; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Male; Metformin; Middle Aged; Nausea; Peptides; Thiazolidinediones; Venoms; Vomiting; Weight Loss

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Humans; Hypoglycemic Agents; Metformin; Peptides; Research Design; Thiazolidinediones; Venoms