Efficacy and Safety of Incretin Therapy in Type 2 Diabetes

Abstract

EWER THAN HALF OF US ADULTS with type 2 diabetes reach a hemoglobin A 1c (HbA 1c ) level of less than 7% despite several available therapies. 1 Ineffective implementation of existing pharmacotherapies is a significant factor contributing to suboptimal care. 2 However, efficacy of available therapies, even when used appropriately, diminishes as the disease progresses because of a steady, relentless decline in pancreatic beta cell function. 3 Furthermore, current therapies for type 2 diabetes are often limited by adverse effects such as weight gain, edema, or hypoglycemia, and most do not target postprandial hyperglycemia effectively. Therefore, therapies targeting the decline in pancreatic beta cell function without causing weight gain and with minimal adverse effects are desirable.Recently, improved understanding of the incretin effect on the pathophysiology of type 2 diabetes has led to development of new hypoglycemic agents. The incretin effect is the augmentation of glucose-stimulated insulin secretion by intestinally derived peptides, which are released in the presence of glucose or nutrients in the gut. 4 The theory evolved from the observation that an oral glucose load was more effective at releasing insulin compared with the same amount of glucose given intravenously. 5 The actions of incre-

Medical management of hyperglycaemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy

“…In addition, meta-analyses and reviews have summarised and compared the glucose-lowering effectiveness and other characteristics of the medications [35][36][37]. The aim here is to provide enough information to justify the choices of medications, the order in which they are recommended and the use of combinations of therapies.…”

Medical Therapy for Obesity

“…In human beings, exenatide reduces fasting and postprandial glucose levels, slows gastric emptying, and decreases food intake by 19%. 33 A systematic review of incretin therapy in type 2 diabetes 34 showed a weight loss of 2.37 kg for all GLP-1 analogs versus control, 1.44 for exenatide versus placebo injection, and 4.76 for exenatide versus insulin (which often leads to weight gain). A 24-week, multicenter, randomized, placebo-controlled clinical trial of exenatide enrolled diabetics poorly controlled with either metformin or sulfonylurea with a HbA 1c between 6.6% and 10.0% and a BMI between 25.0 and 39.9 kg/m 2 .…”

Chances and risks of SGLT2 inhibitors

“…Insulin can be substituted either directly by (in most cases SC) injection or by indirect means to elicit liberation from stores in the pancreas. This is achieved for example by sulfonylureas (Groop 1992) or incretin mimetics (glucagon-like peptide (GLP)-1 analogues and DPP4 inhibitors, Amori et al 2007;Drucker 2007). The aim of diabetes therapy is to maintain blood glucose level in a narrow range close to the physiological level.…”

“…Each class of antidiabetics has its own side effects and drawbacks; some classes, e.g. the GLP-1 analogues or the DPP4 inhibitors (DPP4-dipeptidylpeptidase 4) are rather new (for review, see for example Amori et al 2007;Drucker 2007) so that their place in diabetes therapy cannot yet be fully determined. SGLT2 inhibitors provide a new option and may help to increasingly improve blood glucose control together with existing antidiabetics.…”