Redefining the role of thiazolidinediones in the management of type 2 diabetes

There is a need to evaluate oral glucose-lowering agents not only for their value in achieving glycemic control but also for their impact on cardiac risk factor modification. This article reviews the evidence base for the two thiazolinediones currently available, pioglitazone and rosiglitazone. These drugs exert their effects through actions affecting metabolic control, lipid profiles, and the vascular wall. They have been shown to be as efficacious in establishing glycemic control, in both monotherapy and combination therapy regimens, as more traditional oral agents, and may be able to sustain that control in the long term. Both thiazolidinediones have demonstrated favorable effects on markers of cardiovascular disease. Evidence from the large PROactive outcomes study suggests that pioglitazone may exert protective effects in patients with type 2 diabetes and macrovascular disease. Thiazolidinediones are generally well tolerated but they can cause weight gain, induce fluid retention, and may contribute to bone loss in postmenopausal women. The place of thiazolidinediones in the management of type 2 diabetes is well established. The potential for additional benefits in reducing macrovascular risk encourages further long-term study of these agents

Lixisenatide: evidence for its potential use in the treatment of type 2 diabetes

Lixisenatide is a once-daily glucagon-like peptide 1 (GLP-1) receptor agonist mimicking several favorable actions of endogenous GLP-1 that result in improved glycemic control with little or no hypoglycemia and weight loss. Phase II trials have shown that lixisenatide 20 μg once daily restores first-phase insulin release in patients with type 2 diabetes and improves the second-phase insulin response. Administered once or twice daily for 4 weeks, it significantly reduced postprandial and fasting blood glucose levels, and glycosylated hemoglobin (HbA1c). The efficacy and safety of lixisenatide once daily is being assessed in the GETGOAL Phase III clinical trial program. Results have shown beneficial effects on HbA1c compared with placebo in combination with commonly used antidiabetes agents, with no increased risk of hypoglycemia and with beneficial weight reduction. Adverse effects were similar to those observed for available GLP-1 receptor agonists, the most frequent being gastrointestinal. Both GLP-1 receptor agonists and long-acting insulin analogs have demonstrated protective effects on beta cells in preclinical studies. This, along with the pronounced effect of lixisenatide on postprandial plasma glucose, provides a rationale for combining it with long-acting basal insulin analogs, in the hope that the additive effects on glycemic control combined with a potential benefit on islet cells may lead to a new treatment approach to control blood glucose better and prevent long-term complications in patients with type 2 diabetes

Insulin Glargine in the Treatment of Type 1 and Type 2 Diabetes

Insulin glargine is an analogue of human insulin that is modified to provide a consistent level of plasma insulin over a long duration. Pharmacokinetic and pharmacodynamic studies show that a single injection of insulin glargine leads to a smooth 24-hour time–action profile with no undesirable pronounced peaks of activity. In clinical trials, this profile has been associated with at least equivalent, if not better, glycemic control than other traditional basal insulins and a significantly lower rate of overall and nocturnal hypoglycemia. The convenience of a once-daily injection, a lack of need for resuspension (insulin glargine is a clear solution when injected), and lower rates of hypoglycemia should translate into improvements in patient treatment satisfaction. This review appraises the evidence for the view that insulin glargine represents an advance in basal insulin therapy for both type 1 and type 2 diabetes patients

Inhaled human insulin (Exubera®): clinical profile and patient considerations

Inhaled human insulin (Exubera®) is a rapid-acting regular human insulin administered by oral inhalation before meals. It provides a non-invasive alternative to multiple subcutaneous injections for the treatment of hyperglycemia in adult patients with type 1 and type 2 diabetes. Compared with subcutaneous rapid-acting insulin analogs, Exubera provides equivalent HbA1c control. As a monotherapy or in combination with oral agents, Exubera also provides greater glycemic control than oral agents alone, at least in patients with high levels of HbA1c. Exubera demonstrates improved patient satisfaction compared with subcutaneous insulin or oral agents alone. When offered as a treatment option together with standard treatments in uncontrolled patients naïve to insulin, Exubera increases acceptance of insulin therapy three-fold compared with patients offered standard regimens only. Exubera is well tolerated in comparison to subcutaneous insulin, with a similar incidence of mild to moderate hypoglycemia. Although cough is a common adverse effect early in therapy, this leads to treatment discontinuations in less than 1% of patients. Despite an increased incidence of insulin antibodies compared with subcutaneous administration, and a consistent but minor impact on pulmonary function, long-term safety data of up to 4 years continue to support the safety profile of Exubera

Guidelines for type 2 diabetes: keeping a finger on the pulse

Cardiovascular disease remains the biggest cause of morbidity and mortality in patients with type 2 diabetes.1 Individual drugs from two classes of glucose-lowering agents, glucagon-like peptide-1 (GLP-1)receptor agonists and sodium-glucose cotransporter-2 (SGLT2) inhibitors, have been shown in recent clinical trials to improve cardiovascular outcomes in patients with type 2 diabetes at high risk of cardiovascular disease. These new data are reflected in guidelines from several professional associations, but not in the National Institute for Health and Care Excellence (NICE) guidelines in the UK.2 We believe that NICE and other national and international health authorities should respond rapidly to new data, particularly when there is potential to improve outcomes and save lives

Exenatide once weekly: clinical outcomes and patient satisfaction

Exenatide once-weekly is effective, well tolerated in patients with T2DM and should be a useful addition to the available range of anti-diabetes treatments

How the perceived neighbourhood environment influences active living in older dwellers of an Asian ultra-dense metropolis

The way older adults perceive their neighbourhood environment may determine their levels of physical activity. We examined the associations of perceived neighbourhood environmental attributes with accelerometry-assessed and self-reported physical activity and sedentary time in Hong Kong Chinese older adults. In doing so, we estimated the inter-relationships among perceived environmental attributes, the mediating role of physical activity in the environment-sedentary time nexus and the moderating role of sex. We used data from the Active Lifestyle and the Environment in Chinese Seniors (ALECS) project collected on older adults (N = 909; ≥65 years) living in neighbourhoods varying in walkability and socio-economic status (71 % response rate). Self-reported physical activity and perceived neighbourhood attributes were assessed with validated questionnaires. Accelerometer-based physical activity and sedentary time were collected in 402 participants. Older adults who perceived their neighbourhood to be walkable, safe, aesthetically pleasing and equipped with public sitting facilities engaged in more physical activity and less sedentary time. Curvilinear relations of perceived residential density and activity-friendly urban design features indicated that extreme levels of density may not be optimal for older adults to adopt an active lifestyle because they do not provide sufficient space for sitting facilities and greenery and do not result in better perceptions of neighbourhood walkability when compared to areas with moderate-to-high levels of density. Creative solutions for the incorporation of greenery and public places for sitting in megacities are needed

Repeatability of self-report measures of physical activity, sedentary and travel behaviour in Hong Kong adolescents for the iHealt(H) and IPEN- adolescent studies

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