PIONEER REAL Japan: Primary results from a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.

Aims/introduction: PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice.

Materials And Methods: Adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34-44 weeks. The primary endpoint was change in glycated hemoglobin (HbA) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs).

PIONEER REAL Japan: Baseline characteristics of a multicenter, prospective, real-world study of oral semaglutide in adults with type 2 diabetes in clinical practice in Japan.

Aims/introduction: PIONEER REAL Japan was a non-interventional, multicenter, prospective study investigating oral semaglutide in adults with type 2 diabetes in routine clinical practice. We report baseline characteristics of participants enrolled in this study.

Materials And Methods: Adults aged ≥20 years with type 2 diabetes but no previous treatment with injectable glucose-lowering medication were enrolled.

Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study.

Aim: To assess the in-market use of Saxenda (liraglutide 3.0 mg) and Victoza (liraglutide 1.2 mg/1.

Risk of Thyroid Cancer Associated with Use of Liraglutide and Other Antidiabetic Drugs in a US Commercially Insured Population.

Background: Quantify association between the glucagon-like peptide-1 receptor agonist liraglutide and risk of thyroid cancer (TC) compared to other antidiabetics.

Patients And Methods: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US health plan (2010-2014) and followed for a median of 17 months. Thyroid cancer cases during follow-up were identified via a validated algorithm.

A joint industry-sponsored data monitoring committee model for observational, retrospective drug safety studies in the real-world setting.

Purpose: To share better practice in establishing data monitoring committees (DMCs) for observational, retrospective safety studies with joint-industry sponsorship.

Methods: A DMC model was created to monitor data from an observational, retrospective, post-authorization safety study investigating risk of medullary thyroid cancer in patients treated with long-acting glucagon-like peptide-1 receptor agonists (LA GLP-1RAs) (NCT01511393). Sponsors reviewed regulatory guidelines, best practice and sponsors' standard operation procedures on DMCs.

Liraglutide use and evaluation of pancreatic outcomes in a US commercially insured population.

Aims: Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5-year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs).

Materials And Methods: Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010-2014) were included.

Is there an association between liraglutide use and female breast cancer in a real-world setting?

Background: Liraglutide is a human glucagon-like peptide-1 receptor agonist approved for treatment of adults with type 2 diabetes mellitus at a maximum dose of 1.8 mg/day (Victoza) and more recently at 3.0 mg/day for weight management (Saxenda).

Performance of claims-based algorithms for identifying incident thyroid cancer in commercial health plan enrollees receiving antidiabetic drug therapies.

Background: Thyroid cancer incidence is increasing in the United States (US) and many other countries. The objective of this study was to develop and evaluate algorithms using administrative medical claims data for identification of incident thyroid cancer.

Methods: This effort was part of a prospective cohort study of adults initiating therapy on antidiabetic drugs and used administrative data from a large commercial health insurer in the US.

A prospective, claims-based assessment of the risk of pancreatitis and pancreatic cancer with liraglutide compared to other antidiabetic drugs.

Aim: We evaluated the relationship between liraglutide and acute pancreatitis or pancreatic cancer in an ongoing post-marketing safety assessment programme.

Methods: Initiators of liraglutide, exenatide, metformin, pioglitazone or groups containing initiators of dipeptidyl peptidase-4 inhibitors or sulfonylureas were identified in a US commercial health insurance claims database (1 February 2010 to 31 March 2013) and followed for a median of 15 months. We estimated incidence rates (IR/100 000 person-years), rate ratio (RR) and 95% confidence intervals (CI) of new insurance claims with diagnoses of primary inpatient acute pancreatitis or pancreatic cancer from Poisson regression models.

The effect of chronic heart failure and type 2 diabetes on insulin-stimulated endothelial function is similar and additive.

Aim: Chronic heart failure is associated with endothelial dysfunction and insulin resistance. The aim of this investigation was to study insulin-stimulated endothelial function and glucose uptake in skeletal muscles in patients with heart failure in comparison to patients with type 2 diabetes.

Methods: Twenty-three patients with systolic heart failure and no history of diabetes, seven patients with both systolic heart failure and type 2 diabetes, 19 patients with type 2 diabetes, and ten healthy controls were included in the study.

Endothelial function is unaffected by changing between carvedilol and metoprolol in patients with heart failure--a randomized study.

Background: Carvedilol has been shown to be superior to metoprolol tartrate to improve clinical outcomes in patients with heart failure (HF), yet the mechanisms responsible for these differences remain unclear. We examined if there were differences in endothelial function, insulin stimulated endothelial function, 24 hour ambulatory blood pressure and heart rate during treatment with carvedilol, metoprolol tartrate and metoprolol succinate in patients with HF.

Methods: Twenty-seven patients with mild HF, all initially treated with carvedilol, were randomized to a two-month treatment with carvedilol, metoprolol tartrate or metoprolol succinate.

The influence of parental history of diabetes and offspring birthweight on offspring glucose metabolism in adulthood.

Background: Links are well established between both family history of diabetes and reduced birthweight and increased risk of diabetes in adulthood.

Objectives: 1) To investigate the influence of parental history of type 2 diabetes (T2DM) on offspring birthweight and adult offspring glucose tolerance status in non-diabetic offspring of patients with T2DM and 2) to study the associations of birthweight with measures of pancreatic beta-cell function and insulin sensitivity.

Design: Family cohort study.

Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes.

Objective: To examine the association between selected glucose-lowering medications and left ventricular (LV) diastolic function in patients with diabetes.

Design: Retrospective cohort study (years 2005-2008).

Methods: Echocardiograms of 242 patients with diabetes undergoing coronary angiography were analyzed.

Metoprolol compared to carvedilol deteriorates insulin-stimulated endothelial function in patients with type 2 diabetes - a randomized study.

Aim: Studies of beta blockade in patients with type 2 diabetes have shown inferiority of metoprolol treatment compared to carvedilol on indices of insulin resistance. The aim of this study was to examine the effect of metoprolol versus carvedilol on endothelial function and insulin-stimulated endothelial function in patients with type 2 diabetes.

Method: 24 patients with type 2 diabetes were randomized to receive either 200 mg metoprolol succinate or 50 mg carvedilol daily.

Effects of acute and chronic attenuation of postprandial hyperglycemia on postglucose-load endothelial function in insulin resistant individuals: is stimulation of first phase insulin secretion beneficial for the endothelial function?

The aim of the study is to determine if attenuation of postprandial hyperglycemia, by acutely and chronically enhancing postprandial insulin secretion in insulin-resistant individuals, improves the endothelial dysfunction. We assessed postoral glucose-load endothelial function in 56 insulin-resistant subjects with the Flow-Mediated-Dilation (FMD) technique. We randomized subjects to intervention/control group, and examined the acute and chronic effect of nateglinide, an oral antidiabetic drug of rapid action.

Effects of oral glucose load on endothelial function and on insulin and glucose fluctuations in healthy individuals.

Background/aims: Postprandial hyperglycemia, an independent risk factor for cardiovascular disease, is accompanied by endothelial dysfunction. We studied the effect of oral glucose load on insulin and glucose fluctuations, and on postprandial endothelial function in healthy individuals in order to better understand and cope with the postprandial state in insulin resistant individuals.

Methods: We assessed post-oral glucose load endothelial function (flow mediated dilation), plasma insulin, and blood glucose in 9 healthy subjects.

Quinapril treatment increases insulin-stimulated endothelial function and adiponectin gene expression in patients with type 2 diabetes.

Objective: Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality and improve endothelial function in type 2 diabetic patients. We hypothesized that 2 months of quinapril treatment would improve insulin-stimulated endothelial function and glucose uptake in type 2 diabetic subjects and simultaneously increase the expression of genes that are pertinent for endothelial function and metabolism.

Methods: Twenty-four type 2 diabetic subjects were randomized to receive 2 months of quinapril 20 mg daily or no treatment in an open parallel study.

Influence of fish oil supplementation on in vivo and in vitro oxidation resistance of low-density lipoprotein in type 2 diabetes.

Objective: Fish oil supplement has been proposed as a non-pharmacological strategy to correct the atherogenic lipid profile associated with type 2 diabetes mellitus. However, fish oil may have deleterious effects on lipid peroxidation and glycemic control.

Design: In this study, 44 type 2 diabetic patients were randomized to vitamin E standardized (53.

Effect of fish oil versus corn oil supplementation on LDL and HDL subclasses in type 2 diabetic patients.

Objective: The increased risk of coronary heart disease associated with type 2 diabetes may be partially explained by dyslipidemia characterized by high plasma triacylglycerol (TAG), low HDL cholesterol, and a predominance of atherogenic small dense LDLs. Fish oil reduces plasma TAG and has previously been shown to improve the distribution of LDL subclasses in healthy subjects and might, therefore, be a good nonpharmacological treatment for type 2 diabetic patients. In the present study, we investigate the effect of fish oil supplementation on the fasting lipid profile, including LDL and HDL subclasses.

Prolonged QTc interval predicts mortality in patients with Type 1 diabetes mellitus.

Aims: To evaluate prolonged QTc interval and QT dispersion as predictors of all-cause and cardiovascular mortality after adjustment for well-established risk factors in Type 1 diabetic patients.

Methods: From a cohort of all adult Type 1 diabetic patients, duration of diabetes >or= 5 years, attending the clinic in 1984 and followed in an observational study for 10 years (n = 939), all subjects with resting baseline electrocardiograms were identified (n = 697, 360 males). The QT length was measured and corrected for heart rate (QTc).

QTc interval length and QT dispersion as predictors of mortality in patients with non-insulin-dependent diabetes.

Patients with non-insulin-dependent diabetes (NIDDM) are at independent risk of cardiovascular death. The reason is only partially understood. The aim of our study was therefore to evaluate the impact of corrected QT interval length (QTc) and QT dispersion (QT-disp) on mortality in a cohort of 324 Caucasian NIDDM patients.

Lack of synergism between long-term poor glycaemic control and three gene polymorphisms of the renin angiotensin system on risk of developing diabetic nephropathy in type I diabetic patients.

Aims/hypothesis: Reports on a putative synergism between poor glycaemic control and carriage of the angiotensin II type 1 receptor (AGTR1) C1166-allele and risk of diabetic nephropathy have been conflicting. Therefore, we investigated the interaction between long-term glycaemic control and three polymorphisms in the genes coding for AGTR1 (A1166-->C), angiotensin converting enzyme (ACE/ID) and angiotensinogen (M235T) on risk of developing diabetic nephropathy. Furthermore, we investigated the relation between a random measurement and long-term measurements of haemoglobin A1c (HbA1c).