incretin 2016

AIMS: Liraglutide is marketed in Europe as Victoza® (1.2 mg/1.8 mg), indicated for glycaemic control in type 2 diabetes, and Saxenda® (3.0 mg), indicated for weight management in adults with obesity. We performed a post-authorization safety study (PASS) to assess the in-market use of Saxenda® and Victoza® according to approved indications and posology. MATERIALS AND METHODS: This retrospective, non-interventional study was conducted at 41 sites between December 2016 and May 2019...

BACKGROUND: Several new antidiabetic medicines (GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors) have been approved by the European Medicines Agency since 2006. The aim of this study was to evaluate the uptake of new antidiabetic medicines in European countries over a 10-year period. METHODS: The study used IQVIA quarterly value and volume sales data January 2006-December 2016. The market uptake of new antidiabetic medicines together with intensity of prescribing policy for all antidiabetic medicines were estimated for Austria, Croatia, France, Germany, Hungary, Italy, Poland, Slovenia, Spain, Sweden, and the United Kingdom...

INTRODUCTION: Real-world data indicate that sodium glucose transporter-2-inhibitor therapy and/or incretin mimetics are not widely prescribed in type-2 diabetics with atherosclerotic vascular disease. We hypothesized that incretin-mimetic therapy is associated with better overall survival and 1-year mortality in type-2 diabetics following myocardial revascularization. METHODS: Hospitalized type-2 diabetics of the Departments of Cardiology and Cardiothoracic Surgery (University Hospital Halle) who needed myocardial revascularization (PCI or CABG) in 2016 were included in this observational study: group 1 (incretin-mimetic therapy), group 2 (insulin therapy without incretin mimetics) and group 3 (oral diabetes medication without incretins or insulin)...

BACKGROUND: National treatment guidelines recommend glucagon-like peptide receptor agonists (GLP-1 RAs) as add-on therapy to oral agents. However, GLP-1 RAs in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors is not recommended due to a lack of evidence. OBJECTIVE: This case series aims to describe the efficacy and safety of once-weekly GLP-1 RAs administered concomitantly with DPP-4 inhibitors in patients with type 2 diabetes. METHODS: A retrospective chart review of electronic medical records at a free health clinic was conducted between July 2014 and September 2016...

According to the data, there are 387 million people with diabetes in the world, and the number of people with diabetes is expected to reach 600 million by 2035 (Nature Reviews Endocrinology, 14, 2018, Zheng et al.). At present, there are nearly 110 million diabetic patients in China, the incidence of which is increasing (Diabetologia, 61, 2018, Ma). Islet β cell apoptosis and proliferation is an important basis for the occurrence and development of diabetes. It has been reported that enhancing the activity of incretin-cAMP signaling pathway can also promote islet β cell proliferation, reduce β cell apoptosis and promote insulin secretion (Diabetologia, 59, 2016, Iida et al...

BACKGROUND AND AIMS: One cohort and several basic science studies have raised suspicion about an association between incretin therapies and cholangiocarcinoma. Our aim was to verify the occurrence of CC in relation to incretin-based medication use versus any antidiabetic treatment in an unselected population of diabetic patients. METHODS: A population-based matched case-control study was conducted using administrative data from the Region of Piedmont (4,400,000 inhabitants), Italy...

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), affecting over 25% of the general population worldwide, is characterized by a spectrum of clinical and histological manifestations ranging from simple steatosis (>5% hepatic fat accumulation without inflammation) to non-alcoholic steatohepatitis (NASH) which is characterized by inflammation, and finally fibrosis, often leading to liver cirrhosis, and hepatocellular carcinoma. Up to 70% of patients with type 2 diabetes mellitus (T2DM) have NAFLD, and diabetics have much higher rates of NASH compared with the general non-diabetic population...

BACKGROUND AND AIMS: There are concerns that incretin-based antidiabetic drugs - including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists - increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. METHODS AND RESULTS: Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry...

OBJECTIVES: To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents. DESIGN: Population-based cohort study. SETTING: Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD). PARTICIPANTS: Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016...

This review presents the scope of research presented in an October 2016 lecture pertaining to the award of the 2015 Max Bergmann Medal. The advancement in synthetic and biosynthetic chemistry as applied to the discovery of novel macromolecular drug candidates is reviewed. The evolution of the technology from the design, synthesis, and development of the first biosynthetic peptides through the emergence of peptide-based incretin agonists that function by multiple biological mechanisms is exemplified by the progression of such peptides from preclinical to clinical study...

AIMS: Mixed evidence exists for the effect of incretin-based therapies on osteoporosis in type-2 diabetes. Therefore, we conducted a cohort study to determine the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and common osteoporotic "fragility fractures" (upper extremity, hip, spine). METHODS: The UK-based Clinical Practice Research Datalink was used to identify adults without prior fractures receiving a new anti-diabetic drug or a new type-2 diabetes diagnosis between 2007 and 2016...

Patients with type 2 diabetes mellitus (T2DM) experience many cardiovascular complications. Several studies have demonstrated the cardioprotective effects of incretin-based therapies; however, there are few studies on the effects of long-term incretin-based therapies on cardiovascular events. Therefore, the present study conducted a systematic review and network meta-analysis to evaluate the effects of long-term incretin-based therapies on ischaemic diseases. We searched PubMed, CENTRAL, and Clinicaltrial.gov to retrieve randomised control trials reported until December 2016 and enrolled only RCTs with more than a 1-year follow-up...

OJBECTIVE: To explore temporal trends in antidiabetes drug (ADD) prescribing and intensification patterns, along with glycemic levels and comorbidities, and possible benefits of novel ADDs in delaying the need for insulin initiation in patients diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes aged 18-80 years, who initiated any ADD, were selected ( n = 1,023,340) from the U.S. Centricity Electronic Medical Records. Those who initiated second-line ADD after first-line metformin were identified (subcohort 1, n = 357,482); the third-line therapy choices were further explored...

AIMS: In patients with type 2 diabetes, incretin-based therapies can improve glucose control without increased weight gain or hypoglycemia. Incretin-based drugs added to insulin therapy in type 1 diabetes (T1DM) have also been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to assess the efficacy and safety of incretin-based therapies in patients with T1DM. METHODS: We systematically searched Medline, EMBASE, and Cochrane Central Register of Controlled Trials for relevant studies published before August 25, 2016...

BACKGROUND: Recent findings indicate that incretin hormones and incretin-based therapies may affect the metabolism of lipoproteins, although the corresponding mechanisms are not clearly defined. OBJECTIVE: To summarize the available data on the mechanisms linking incretins with the characteristics of serum lipoproteins and discuss the clinical implications of these relationships. METHODS: PubMed was searched using the terms "incretins", "GLP-1", "GIP" and "lipids", "dyslipidemia", "triglycerides", "apolipoprotein B48"...

OBJECTIVE: Nephropathy is among the most common and most devastating complications of diabetes mellitus. Recent data suggest that there is a multifaceted interaction between the kidney and antidiabetic drugs. Thus, the deterioration of renal function may result in important changes in the pharmacokinetic and pharmacodynamic properties of glucose-lowering compounds. Additionally, drugs that exert their antidiabetic properties through the inhibition of proximal glucose reabsorption are now available whereas accumulating evidence suggests that some of these drugs may exert renoprotective properties that are independent of their effect on carbohydrate metabolism...

Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4 ) in DPP4 gene knockout (gko) mice...

BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...

BACKGROUND: Dumping syndrome, a common complication of esophageal, gastric or bariatric surgery, includes early and late dumping symptoms. Early dumping occurs within 1 h after eating, when rapid emptying of food into the small intestine triggers rapid fluid shifts into the intestinal lumen and release of gastrointestinal hormones, resulting in gastrointestinal and vasomotor symptoms. Late dumping occurs 1-3 h after carbohydrate ingestion, caused by an incretin-driven hyperinsulinemic response resulting in hypoglycemia...

Type 2 diabetes mellitus (T2DM) is a fast progressing disease reaching pandemic proportions. T2DM is specifically harmful because of its severe secondary complications. In the course of the disease, most patients require treatment with oral antidiabetic drugs (OADs), for which a relatively large number of different options are available. The growing number of individuals affected by T2DM as well as marked interindividual differences in the response to treatment call for individualized therapeutic regimens that can maximize treatment efficacy and thus reduce side effects and costs...