Incretin therapy for diabetes mellitus type 2
Purpose of review Among the gastrointestinal hormones, the incretins: glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 have attracted interest because of their importance for the development and therapy of type 2 diabetes and obesity. New agonists and formulations of particularly the GLP-1 receptor have been developed recently showing great therapeutic efficacy for both diseases. Recent findings The status of the currently available GLP-1 receptor agonists (GLP-1RAs) is described, and their strengths and weaknesses analyzed. Their ability to also reduce cardiovascular and renal risk is described and analysed. The most recent development of orally available agonists and of very potent monomolecular co-agonists for both the GLP-1 and GIP receptor is also discussed. Summary The GLP-1RAs are currently the most efficacious agents for weight loss, and show potential for further efficacy in combination with other food-intake-regulating peptides. Because of their glycemic efficacy and cardiorenal protection, the GLP-1 RAs will be prominent elements in future diabetes therapy.
ConclusionsRepeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.
Obesity and related metabolic disorders, including type 2 diabetes mellitus (T2DM), alarmingly grow up in the modern society thus representing a serious issue for endocrinology and medicine. Obesity is the major risk factor for T2DM , however, not all obese individuals ultimately develop T2DM. Nevertheless, mechanisms linking obesity to T2DM are being extensively studied.
Abstract T1R3 protein, the main subunit of the sweet taste receptor and receptor of amino acid taste, is expressed in the epithelium of the tongue and gastrointestinal tract, in β cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing evidences on the involvement of T1R3 in the control of carbohydrate and lipid metabolism, and the control of incretin and insulin production were obtained. In the study on Tas1r3-gene knockout mouse strain and parent C57BL/6J strain as a control, the data on the effect of T1R3 on morphological characteristics of Langerhans islets in the pancreas wer...
From the Incretin Concept and the Discovery of GLP-1 to Today's Diabetes Therapy Jens Juul Holst* Department of Biomedical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark Researchers have been looking for insulin-stimulating factors for more than 100 years, and in the 1960ties it was definitively proven that the gastrointestinal tract releases important insulinotropic factors upon oral glucose intake, so-called incretin hormones. The first significant factor identified was the duodenal glucose-dependent insulinotropic polypeptide, GIP, wh...
Conclusions: Bariatric surgery appears to be capable of partially reversing the obesity-related epigenome. The identification of potential epigenetic biomarkers predictive for the success of bariatric surgery may open new doors to personalized therapy for severe obesity. Introduction Obesity is currently a huge healthcare problem, worldwide, and is a risk factor for several diseases such as type 2 diabetes (T2D), cardiovascular disease and cancer (1). As the prevalence of obesity reaches pandemic proportions, this metabolic disease is estimated to become the biggest cause of mortality in the near future (2). In fact,...
Bariatric surgery is currently the best treatment for type 2 diabetes mellitus (DM2) in patients with obesity. Although different surgical techniques produce different results, better glycemic control is achieved with surgical procedures compared to clinical treatments [1 –3].
Background: Type 2 diabetes mellitus is a disease correlated with obesity. Obese patients has suppressed incretin effect and inbalance of glycemic homeostasis. Studies have shown improvement in DM2 after Roux-en-Y gastric bypass (RYGB). The mechanisms of glycemic control may be long-term and short-term. The mechanisms of early action are linked to caloric restriction, improvement of insulin resistance, pancreatic beta cell function and return of the incretin effect through the increase of GLP1 and GIP, but data are conflicting.
ConclusionsBased on these results, the pharmacology of LY3298176 translates from preclinical to clinical studies. LY3298176 has the potential to deliver clinically meaningful improvement in glycaemic control and body weight. The data warrant further clinical evaluation of LY3298176 for the treatment of T2DM and potentially obesity.
To the Editor Inge et al have shown that bariatric surgery has a greater association than medical treatment alone in achieving an improvement of type 2 diabetes mellitus and its comorbidities in obese adolescents. The mechanism seems to go beyond the magnitude of weight loss alone and include an improvement in incretin profiles, insulin secretion, and insulin sensitivity.
Obesity and type 2 diabetes mellitus (T2DM) have become a substantial burden on public health in the last century and advocate different strategies to mitigate them . Proximal small bowel diversion bears prominent beneficial metabolic effects associated with augmentation of the incretin system and accelerated glucose handling in the distal part of the gut [2, 3]. Roux-en-Y gastric bypass (RYGB) surgery exhibits these advantages [4 –6] and is an effective tool for weight reduction and glycemic control .