Incretin-based Therapies for Type 2 Diabetes Mellitus: Effects on Insulin Resistance

Abstract

Insulin resistance has been associated with the development of type 2 diabetes, obesity, hypertension, dyslipidemia, atherosclerosis, and thus with increased cardiovascular morbidity and mortality. Insulin resistance precedes the onset of type 2 diabetes by many years. Targeting the pathophysiologic defects that characterize the onset of diabetes is more likely to achieve a durable glucose control and to delay disease progression. Incretins are gut-derived peptides that stimulate in a glucose-dependent mechanism insulin secretion and action. Glucose-like peptide 1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors both decrease fasting and postprandial glucose levels. In addition, GLP-1 analogues promote weight loss and exert a favorable effect on several cardiovascular risk factors. Data from human and experimental studies implicate that GLP-1 analogues and to a less extend DPP-4 inhibitors enhance insulin sensitivity. This review summarizes the current knowledge regarding the impact of GLP-1 analogues and DPP-4 inhibitors on insulin resistance.

Liraglutide, a Glucagon-Like Peptide-1 Analog, Increased Insulin Sensitivity Assessed by Hyperinsulinemic-Euglycemic Clamp Examination in Patients with Uncontrolled Type 2 Diabetes Mellitus

“…Recently, clinical attention has been focused on the incretin-related medicines such as GLP-1 analog as a new treatment strategy for diabetes and obesity [ 5 , 6 ]. It has been suggested that GLP-1 analog may have the ability of enhancing insulin sensitivity [ 7 ], but some studies have demonstrated controversial clinical results regarding the augmentation of insulin sensitivity by GLP-1 analog [ 11 – 13 ]. In the present study, we investigated the change in insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp.…”

“…Investigations of impaired insulin sensitivity are mainly involved in the pathogenesis of type 2 DM. Several animal studies have demonstrated that GLP-1 and GLP-1 analog exhibit the ability of improving insulin sensitivity [ 7 ]. A GLP-1 analog has been shown to activate AMP-activated protein kinase (AMPK) in in vitro experiments [ 8 ].…”

Insulin sensitivity and secretion and adipokine profile in patients with Cushing’s disease treated with pasireotide

“…To maintain stable glycaemic values during the study metformin and short-acting insulin were prescribed, even though it is different from what is currently recommended by the guidelines for the management of diabetes mellitus during pasireotide treatment [24]. However, we preferred not to use GLP-1 analogues and DPP-4 inhibitors, to avoid the interference of these drugs on clinical, metabolic parameters (insulin sensitivity) and adipokines [25][26][27][28].…”

Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction

“…Glucagon-like peptide 1 is an endogenous incretin hormone that improves insulin sensitivity with minimal risk of hypoglycemia. Recombinant GLP-1 increases myocardial insulin sensitivity 5 and is cardioprotective during ischemia in model systems. 6 …”