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A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes.

ABSTRACT: Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for the development of cardiovascular disease. With an increasing prevalence of obesity, this risk has increased further. Management of T2DM in obese patients is particularly challenging as treatment with the majority of glucose-lowering agents results in weight gain. Thus, the development of a therapeutic option which could improve glycemic control without weight gain or hypoglycemia, such as the glucagon-like peptide-1 (GLP-1) analog exenatide, is a welcome addition to the currently available therapies in the management of T2DM. With recognition and better understanding of the role of incretin hormones in T2DM, exenatide was developed and introduced into clinical practice in 2005. Both randomized controlled trials and retrospective observational studies have shown that treatment with exenatide not only improves glycemic control, with a low risk of hypoglycemia, but also results in concurrent weight loss and the additional benefit of improvement in cardiovascular risk factors. This article will provide an overview of both short- and long-acting exenatide in the management of T2DM and associated cardiovascular risk factors.

SUBMITTER: Htike ZZ

PROVIDER: S-EPMC3508112 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes.

Htike Zin Z ZZ Khunti Kamlesh K Davies Melanie M

Diabetes therapy : research, treatment and education of diabetes and related disorders 20120316 1

Type 2 diabetes mellitus (T2DM) is a well-recognized risk factor for the development of cardiovascular disease. With an increasing prevalence of obesity, this risk has increased further. Management of T2DM in obese patients is particularly challenging as treatment with the majority of glucose-lowering agents results in weight gain. Thus, the development of a therapeutic option which could improve glycemic control without weight gain or hypoglycemia, such as the glucagon-like peptide-1 (GLP-1) an ...[more]

PMID: 22422427

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Project description:Overweight or obesity contributes to the development of type 2 diabetes mellitus (T2DM) and increases cardiovascular risk. Exenatide, a glucagon-like peptide-1 receptor agonist, significantly reduces glycated hemoglobin (A1C) and body weight and improves cardiovascular risk markers in patients with T2DM. As weight loss alone has been shown to reduce A1C and cardiovascular risk markers, this analysis explored whether weight loss contributed importantly to clinical responses to exenatide once weekly.A pooled analysis from eight studies of exenatide once weekly was conducted. Patients were distributed into quartiles from greatest weight loss (Quartile 1) to least loss or gain (Quartile 4). Parameters evaluated for each quartile included A1C, fasting plasma glucose (FPG), blood pressure (BP), heart rate, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).The median changes from baseline in body weight in Quartiles 1-4 were -6.0, -3.0, -1.0, and +1.0 kg, respectively. All quartiles had reductions in A1C (median changes -1.6, -1.4, -1.1, and -1.2%, respectively) and FPG (-41, -40, -31, and -25 mg/dL, respectively), with the greatest decreases in Quartiles 1 and 2. Most cardiovascular risk markers (except diastolic BP) and liver enzymes improved in Quartiles 1 through 3 and were relatively unchanged in Quartile 4. Higher rates of gastrointestinal adverse events and hypoglycemia were observed in Quartile 1 compared with Quartiles 2 through 4.Exenatide once weekly improved glycemic parameters independent of weight change, although the magnitude of improvement increased with increasing weight loss. The greatest trend of improvement in glycemic parameters, cardiovascular risk factors including systolic BP, LDL-C, total cholesterol, and triglycerides, and in liver enzymes, was seen in the patient quartiles with the greatest reductions in body weight.

Project description:BACKGROUND: Walking is the most popular and most preferred exercise among type 2 diabetes patients, yet compelling evidence regarding its beneficial effects on cardiovascular risk factors is still lacking. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the association between walking and glycemic control and other cardiovascular risk factors in type 2 diabetes patients. METHODS: Three databases were searched up to August 2014. English-language RCTs were eligible for inclusion if they had assessed the walking effects (duration ?8 weeks) on glycemic control or other cardiovascular risk factors among type 2 diabetes patients. Data were pooled using a random-effects model. Subgroup analyses based on supervision status and meta-regression analyses of variables regarding characteristics of participants and walking were performed to investigate their association with glycemic control. RESULTS: Eighteen studies involving 20 RCTs (866 participants) were included. Walking significantly decreased glycosylated haemoglobin A1c (HbA1c) by 0.50% (95% confidence intervals [CI]: -0.78% to -0.21%). Supervised walking was associated with a pronounced decrease in HbA1c (WMD -0.58%, 95% CI: -0.93% to -0.23%), whereas non-supervised walking was not. Further subgroup analysis suggested non-supervised walking using motivational strategies is also effective in decreasing HbA1c (WMD -0.53%, 95% CI: -1.05% to -0.02%). Effects of covariates on HbA1c change were generally unclear. For other cardiovascular risk factors, walking significantly reduced body mass index (BMI) and lowered diastolic blood pressure (DBP), but non-significantly lowered systolic blood pressure (SBP), or changed high-density or low-density lipoprotein cholesterol levels. CONCLUSIONS: This meta-analysis supports that walking decreases HbA1c among type 2 diabetes patients. Supervision or the use of motivational strategies should be suggested when prescribed walking to ensure optimal glycemic control. Walking also reduces BMI and lowers DBP, however, it remains insufficient regarding the association of walking with lowered SBP or improved lipoprotein profiles. TRIAL REGISTRATION: PROSPERO CRD42014009515.

Project description:BACKGROUND:Poor glycemic control is associated with increased risk of cardiovascular disease (CVD) in type 1 diabetes mellitus (T1DM); however, little is known about mechanisms specific to T1DM. In T1DM, myocardial injury can induce persistent cardiac autoimmunity. Chronic hyperglycemia causes myocardial injury, raising the possibility that hyperglycemia-induced cardiac autoimmunity could contribute to long-term CVD complications in T1DM. METHODS:We measured the prevalence and profiles of cardiac autoantibodies (AAbs) in longitudinal samples from the DCCT (Diabetes Control and Complications Trial) in participants with mean hemoglobin A1c (HbA1c) ?9.0% (n=83) and ?7.0% (n=83) during DCCT. We assessed subsequent coronary artery calcification (measured once during years 7-9 in the post-DCCT EDIC [Epidemiology of Diabetes Interventions and Complications] observational study), high-sensitivity C-reactive protein (measured during EDIC years 4-6), and CVD events (defined as nonfatal myocardial infarction, stroke, death resulting from CVD, heart failure, or coronary artery bypass graft) over a 26-year median follow-up. Cardiac AAbs were also measured in matched patients with type 2 diabetes mellitus with HbA1c ?9.0% (n=70) and ?7.0% (n=140) and, as a control for cardiac autoimmunity, patients with Chagas cardiomyopathy (n=51). RESULTS:Apart from HbA1c levels, the DCCT groups shared similar CVD risk factors at the beginning and end of DCCT. The DCCT HbA1c ?9.0% group showed markedly higher cardiac AAb levels than the HbA1c ?7.0% group during DCCT, with a progressive increase and decrease in AAb levels over time in the 2 groups, respectively ( P<0.001). In the HbA1c ?9.0% group, 46%, 22%, and 11% tested positive for ?1, ?2, and ?3 different cardiac AAb types, respectively, similar to patients with Chagas cardiomyopathy, compared with 2%, 1%, and 0% in the HbA1c ?7.0% group. Glycemic control was not associated with AAb prevalence in type 2 diabetes mellitus. Positivity for ?2 AAbs during DCCT was associated with increased risk of CVD events (4 of 6; hazard ratio, 16.1; 95% CI, 3.0-88.2) and, in multivariable analyses, with detectable coronary artery calcification (13 of 31; odds ratio, 60.1; 95% CI, 8.4-410.0). Patients with ?2 AAbs subsequently also showed elevated high-sensitivity C-reactive protein levels (6.0 mg/L versus 1.4 mg/L in patients with ?1 AAbs; P=0.003). CONCLUSIONS:Poor glycemic control is associated with cardiac autoimmunity in T1DM. Furthermore, cardiac AAb positivity is associated with an increased risk of CVD decades later, suggesting a role for autoimmune mechanisms in the development of CVD in T1DM, possibly through inflammatory pathways.

Project description:BackgroundCardiovascular disease (CVD) is the most common complication of diabetes mellitus (DM). To prevent morbidity and mortality among patients with type 2 diabetes mellitus (T2DM), optimization of glycemic status and minimizing CVD risk factors is essential. As Nepal has limited data on these CVD risk parameters, we assessed the prevalence of poor glycemic control, CVD risk factors, and their clustering among patients with T2DM.MethodsUsing a cross-sectional study design, we collected data of 366 patients with T2DM. We applied a multistage cluster sampling technique and used the WHO STEPS tools. Binary logistic and Poisson regression was applied to calculate odds and prevalence ratio of clustering of risk factors, considering P< 0.05 statistically significant.ResultsThe mean age of participants was 54.5±10.7 years and 208 (57%) were male. The prevalence of poor glycemic control was 66.4% (95% C.I: 61.5-71.2). The prevalence of smoking, alcohol users, inadequate fruit and vegetables intake and physical inactivity were 18% (95% C.I:14 to 21.9), 14.8% (95% C.I:11.1 to 18.4), 98.1% (95% C.I: 96.7-99.4), and 9.8% (95% C.I:6.7-12.8), respectively. Overall, 47.3% (95% C.I: 42.1-52.4) were overweight and obese, 59% (95% C.I: 52.9-63) were hypertensive, and 68% (95% C.I: 63.2-72.7) had dyslipidemia. Clustering of two, three, four, five and more than five risk factors was 12.6%, 30%, 30%,19%, and 8.7%, respectively. Four or more risk factors clustering was significantly associated with gender, age, level of education, T2DM duration, and use of medication. Risk factors clustering was significantly higher among males and users of anti-diabetic medications with prevalence ratio of 1.14 (95% C.I:1.05-1.23) and 1.09 (95% C.I: 1.09-1.18)], respectively.ConclusionsThe majority of the patients with T2DM had poor glycemic control and CVD risk factors. Policies and programs focused on the prevention and better management of T2DM and CVD risk factors should be implemented to reduce mortality in Nepal.

Project description:Background The value of glycemic control and preexisting cardiovascular disease in determining the risk of major cardiovascular events (MACE) in type 2 diabetes mellitus is uncertain. Intensive glucose control trials suggest that the 9% lower risk of MACE associated with intensive glycemic control, as compared with conventional glycemic control, is only driven by patients with type 2 diabetes mellitus without cardiovascular disease at baseline. Methods and Results We did a meta-analysis of cardiovascular outcome trials dividing patients with or without preexisting cardiovascular disease; we found that the lower risk of MACE is confined to patients with cardiovascular disease at baseline. Compared with placebo, the use of both glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors was associated with a significant 14% lower MACE risk in patients with preexisting cardiovascular disease and with a nonsignificant 2% higher MACE risk in those without preexisting cardiovascular disease ( P for interaction=0.021). The meta-regression analysis of all 12 trials demonstrated a significant ( P=0.002) association between reductions of glycated hemoglobin in glycated hemoglobin A1C. Accordingly, the reduction of MACE expected if all cardiovascular outcome trials had achieved a 0.9% glycated hemoglobin reduction would have been 33%. Routine clinical care data complement the results of cardiovascular outcome trials but with some differences: the lower risk of MACE with sodium-glucose cotransporter-2 inhibitor use is evident in patients with type 2 diabetes mellitus with or without preexisting cardiovascular disease. Conclusions Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists should be included in the therapeutic plan of patients with type 2 diabetes mellitus and overt cardiovascular disease, with due attention paid to improvement of glycemic control, which may amplify their benefit on MACE.

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A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes.

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A review of exenatide: optimizing glycemic control and associated cardiovascular risk factors in type 2 diabetes.

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