Abstract

BackgroundType 2 diabetes is a progressive disease that requires stepwise additions of non-insulin and insulin therapies to meet recommended glycaemic goals. The final stage of intensification may require prandial insulin, adding complexity and increased risks of hypoglycaemia and weight gain.AimsThis review assesses the benefits and risks of adding exenatide twice daily, a glucagon-like peptide 1 receptor agonist, in patients with type 2 diabetes who are currently treated with basal insulin, but have failed to reach their glycaemic goals.Methods and ResultsBased on data from published studies, exenatide has a number of actions that complement basal insulin therapy. Exenatide has been shown to increase glucose-dependent insulin production, suppress abnormal plasma glucagon production, slow gastric emptying, enhance liver uptake of glucose and promote satiety. A recently published randomised clinical trial reported that the addition of exenatide twice daily to titrated basal insulin provided greater glycaemic control than titrated basal insulin alone, and did so without an increase in hypoglycaemic events and with modest weight loss. Exenatide use was associated with gastrointestinal side effects. The recent randomised trial confirmed and extended data from a number of prior observational studies that demonstrated the efficacy and safety of insulin/exenatide combination therapy. Practical considerations for adding exenatide twice daily to ongoing basal insulin are discussed.

Highlights

  • BackgroundType 2 diabetes is a progressive disease that requires stepwise additions of non-insulin and insulin therapies to meet recommended glycaemic goals

  • In patients with type 2 diabetes, the goals of pharmacotherapy are to reduce the risks of microvascular and macrovascular complications by achieving glucose values near the normal range, consistent with glycated haemoglobin (HbA1c) targets

  • Several titration regimens are provided in this review, along with recommendations for down-titration of insulin in patients with minimally elevated fasting plasma glucose levels or an HbA1c < 8%

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Summary

Background

Type 2 diabetes is a progressive disease that requires stepwise additions of non-insulin and insulin therapies to meet recommended glycaemic goals. Aims: This review assesses the benefits and risks of adding exenatide twice daily, a glucagon-like peptide 1 receptor agonist, in patients with type 2 diabetes who are currently treated with basal insulin, but have failed to reach their glycaemic goals. A recently published randomised clinical trial reported that the addition of exenatide twice daily to titrated basal insulin provided greater glycaemic control than titrated basal insulin alone, and did so without an increase in hypoglycaemic events and with modest weight loss. In patients with type 2 diabetes who have failed to reach glycaemic goals, studies suggest that adding exenatide twice daily to actively titrated basal insulin results in robust reductions in HbA1c, modest weight reduction, no significant increase in hypoglycaemia and a possible reduction in insulin dose. Several titration regimens are provided in this review, along with recommendations for down-titration of insulin in patients with minimally elevated fasting plasma glucose levels or an HbA1c < 8%

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