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

Abstract

Aims. Glucagon-like peptide-1 (GLP-1) analog promotes insulin secretion by acting on pancreatic β-cells. This antihyperglycemic treatment for type 2 diabetes mellitus (DM) has attracted increased clinical attention not only for its antihyperglycemic action but also for its potential extrapancreatic effects. We investigated whether liraglutide, a GLP-1 analog, could enhance insulin sensitivity as assessed by the hyperinsulinemic-euglycemic clamp in type 2 DM patients. Materials. We prospectively enrolled 31 uncontrolled type 2 DM patients who were hospitalized and equally managed by guided diet- and exercise-therapies and then introduced to either liraglutide- or intensive insulin-therapy for 4 weeks. Insulin sensitivity was assessed by the glucose infusion rate (GIR) using hyperinsulinemic-euglycemic clamp before and after the therapies. Results. Values of HbA1c, postprandial plasma glucose, and body mass index (BMI) were significantly decreased by hospitalized intensive insulin-therapy or liraglutide-therapy. GIR was significantly increased by liraglutide-therapy but not by insulin-therapy, indicating that liraglutide-therapy significantly enhanced insulin sensitivity. BMI decreased during liraglutide-therapy but was not significantly correlated with changes in GIR. Multivariate logistic regression analysis demonstrated that liraglutide-therapy significantly correlated with increased insulin sensitivity in uncontrolled DM patients. Conclusions. Liraglutide may exhibit favorable effects on diabetes control for type 2 DM patients by increasing insulin sensitivity as an extrapancreatic action. Clinical trial registration Unique Identifier is UMIN000015201.

Clinical Effectiveness of Liraglutide in Type 2 Diabetes Treatment in the Real-World Setting: A Systematic Literature Review

“…The majority of the studies assessed the clinical effectiveness of liraglutide without an active comparator (81.4%; N  = 35) [28, 29, 31, 34, 36–39, 41–49, 51–55, 57, 60–64, 66–71]. Real-world studies with comparators were less frequently observed (18.6%; N  = 8); the most common comparators for liraglutide were: sitagliptin or any DPP-4i ( N  = 6) [32, 33, 35, 40, 56, 58], exenatide ( N  = 3) [33, 35, 50], glimepiride or any other SUs ( N  = 2) [30, 35], pioglitazone or other TZDs ( N  = 1) [35], and MET ( N  = 1) [35]; note: these numbers do not add up because some studies had more than one comparator.…”

“…Of these, 38 were full-text articles [28–34, 36–53, 55–60, 62, 64, 66, 67, 69, 70]. Study attributes and patient baseline characteristics from the included studies are provided in supplementary file 2.…”

Glucagon-like peptide-1 analogues - an efficient therapeutic option for the severe insulin resistance of lipodystrophic syndromes: two case reports

“…Liraglutide has been shown to ameliorate insulin resistance through upregulation of glucose transporter-4 and to decrease oxidative stress and inflammation. It has also been shown to improve endothelial and cardiac function, which might result in increasing systemic insulin sensitivity [12]. Data from studies in diabetic rats showed that exenatide inhibits hepatic gluconeogenesis and increases glucose uptake in the peripheral skeletal muscle with improvement of hepatic and extrahepatic insulin resistance [13].…”

Targeting the gastrointestinal tract to treat type 2 diabetes

“…Similar to exenatide, the main site of action of liraglutide remains unknown. Interestingly, liraglutide has been shown to improve insulin sensitivity in humans, as assessed by the hyperinsulinaemic euglycaemic clamp (Jinnouchi et al 2015), indicating that in addition to its effects on insulin secretion, liraglutide also exhibits beneficial extrapancreatic effects on glycaemia. Liraglutide also passes the blood-brain barrier and it has been shown to bind to neurons within the arcuate nucleus and other sites within the hypothalamus (Secher et al 2014).…”