Switching to Once-Daily Liraglutide From Twice-Daily Exenatide Further Improves Glycemic Control in Patients With Type 2 Diabetes Using Oral Agents

OBJECTIVETo evaluate efficacy and safety of switching from twice-daily exenatide to once-daily liraglutide or of 40 weeks of continuous liraglutide therapy.RESEARCH DESIGN AND METHODSWhen added to oral antidiabetes drugs in a 26-week randomized trial (Liraglutide Effect and Action in Diabetes [LEAD]-6), liraglutide more effectively improved A1C, fasting plasma glucose, and the homeostasis model of β-cell function (HOMA-B) than exenatide, with less persistent nausea and hypoglycemia. In this 14-week extension of LEAD-6, patients switched from 10 μg twice-daily exenatide to 1.8 mg once-daily liraglutide or continued liraglutide.RESULTSSwitching from exenatide to liraglutide further and significantly reduced A1C (0.32%), fasting plasma glucose (0.9 mmol/l), body weight (0.9 kg), and systolic blood pressure (3.8 mmHg) with minimal minor hypoglycemia (1.30 episodes/patient-year) or nausea (3.2%). Among patients continuing liraglutide, further significant decreases in body weight (0.4 kg) and systolic blood pressure (2.2 mmHg) occurred with 0.74 episodes/patient-year of minor hypoglycemia and 1.5% experiencing nausea.CONCLUSIONSConversion from exenatide to liraglutide is well tolerated and provides additional glycemic control and cardiometabolic benefits

Quality of Diabetes Care in U.S. Academic Medical Centers: Low rates of medical regimen change

To assess both standard and novel diabetes quality measures in a national sample of U.S. academic medical centers

Dipeptidyl-peptidase-4 inhibitors and pancreatic cancer: a cohort study

Aims—Dipeptidyl-peptidase-4 inhibitors (DPP-4i) have been implicated with an increased pancreatic cancer risk. We therefore compared pancreatic cancer incidence and diagnostic work-up among initiators of DPP-4i versus sulfonylureas (SU) and thiazolidinediones (TZD). Methods—Medicare claims data were examined in a new-user active-comparator cohort study. Patients >65 years with no prescriptions for DPP-4i, SU or TZD at baseline were included if they had at least two claims for the same drug within 180 days. Using an as-treated approach and propensity score-adjusted Cox models, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Diagnostic work-up was compared using risk ratios (RR). RESULTS—In the DPP-4i vs SU comparison, there were 18,179 DPP4i initiators of which 26 developed pancreatic cancer (follow-up time interquartile range 5–18 months). In the DPP-4i vs TZD comparison there were 29,366 DPP-4i initiators and 52 developed pancreatic cancer. The hazard of pancreatic cancer with DPP-4i was lower relative to SU (HR=0.6, CI 0.4–0.9) and similar to TZD (HR=1.0, CI 0.7–1.4). Excluding first 6 months of follow-up to reduce the potential for reverse causality did not alter results. Probability of diagnostic work-up post-initiation among DPP-4i initiators (79.3%) was similar to TZD (74.1%) (RR=1.06, CI 1.05–1.07) and SU (74.6%) (RR=1.06, CI1.05–1.07). The probability of diagnostic workup pre-index was ~80% for all cohorts. Conclusion—Though limited by sample size and the observed duration of treatment in the US, our well-controlled population based study suggests no increased short-term pancreatic cancer risk with DPP-4i relative to SU or TZD

Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)

OBJECTIVETo determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes.RESEARCH DESIGN AND METHODSThis 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7–11% (previous oral antidiabetes drug [OAD] monotherapy ≥3 months) or 7–10% (previous OAD combination therapy ≥3 months), and BMI ≤45 kg/m2.RESULTSMean A1C values decreased significantly more in the liraglutide groups versus placebo (mean ± SE −1.5 ± 0.1% for both 1.2 and 1.8 mg liraglutide and −0.5 ± 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of β-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient.CONCLUSIONSLiraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control

Incretin-Based Therapies for the Treatment of Type 2 Diabetes: Evaluation of the Risks and Benefits

Limited evidence suggests that GLP-I may also preserve ventricular function and improve outcomes in human subjects with heart failure or myocardial infarction (11,12). [...] both exenatide and liraglutide reduce blood pressure, body weight, and plasma lipid profiles in subjects with type 2 diabetes (13), raising the hope that longterm treatment with these agents may reduce the incidence of cardiovascular events.\n However, two safety issues have been raised - pancreatitis and medullary carcinoma of the thyroid

Secondary fluorescence in WDS:the role of spectrometer positioning

Secondary fluorescence, typically a minor error in routine electron probe microanalysis (EPMA), may not be negligible when performing high precision trace element analyses in multiphase samples. Other factors, notably wavelength dispersive spectrometer defocusing, may introduce analytical artefacts. To explore these issues, we measured EPMA transects across two material couples chosen for their high fluorescence yield. We measured transects away from the fluorescent phase, and at various orientations with respect to the spectrometer focal line. Compared to calculations using both the Monte Carlo simulation code PENEPMA and the semi-analytical model FANAL, both codes estimate the magnitude of SF, but accurate correction requires knowledge of the position of the spectrometer with respect to the couple interface. Positioned over the fluorescent phase or otherwise here results in a factor of 1.2-1.8 of apparent change in SF yield. SF and spectrometer defocusing may introduce systematic errors into trace element analyses, both may be adequately accounted for by modelling. Of the two, however, SF is the dominant error, resulting in 0.1 wt% Zn apparently present in Al at 100 m away from the Zn boundary in an Al/Zn couple. Of this, around 200 ppm Zn can be attributed to spectrometer defocusing.</p

Prochlo: Strong Privacy for Analytics in the Crowd

The large-scale monitoring of computer users' software activities has become commonplace, e.g., for application telemetry, error reporting, or demographic profiling. This paper describes a principled systems architecture---Encode, Shuffle, Analyze (ESA)---for performing such monitoring with high utility while also protecting user privacy. The ESA design, and its Prochlo implementation, are informed by our practical experiences with an existing, large deployment of privacy-preserving software monitoring. (cont.; see the paper

Diabetes Screening With Hemoglobin A1c Versus Fasting Plasma Glucose in a Multiethnic Middle-School Cohort

OBJECTIVETo characterize middle-school students from the HEALTHY study with glycemic abnormalities, specifically high-risk hemoglobin A1c (A1C) (hrA1C; A1C = 5.7–6.4%) and impaired fasting glucose (IFG; fasting plasma glucose [FPG] = 100–125 mg/dL).RESEARCH DESIGN AND METHODSHistory was collected by self-report, physical measurement was collected by trained study staff, and fasting blood was drawn by trained phlebotomists and analyzed centrally.RESULTSAt baseline, among 3,980 sixth graders, 128 (3.2%) had hrA1C and 635 (16.0%) had IFG. Compared with A1C <5.7%, hrA1C was associated with non-Hispanic black race/ethnicity, family history of diabetes, and higher measurements of BMI, waist circumference, and fasting insulin. Compared with FPG <100 mg/dL, IFG was associated with Hispanic ethnicity; increased BMI, waist circumference, and fasting insulin; higher frequency of high blood pressure; and higher mean triglycerides. Two years later, children with hrA1C persisted as hrA1C in 59.4%, and one child (0.8%) developed A1C ≥6.5%; children with IFG persisted with IFG in 46.9%, and seven children (1.1%) developed FPG ≥126 mg/dL. Those with hrA1C compared with IFG had a higher BMI in sixth grade, which persisted to eighth grade.CONCLUSIONSIn the HEALTHY study cohort, hrA1C and IFG define different groups of youth with differentially increased diabetes risk markers. IFG is approximately fivefold more common, but hrA1C is more persistent over time. Optimal screening strategies for diabetes in youth remain unresolved