A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.

Cotadutide is a glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist that may improve kidney function in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). In this phase 2b study, patients with T2D and CKD (estimated glomerular filtration rate [eGFR] of 20 or more and under 90 mL/min per 1.73 m and urinary albumin-to-creatinine ratio [UACR] over 50 mg/g) were randomized 1:1:1:1:1 to 26 weeks' treatment with standard of care plus subcutaneous cotadutide uptitrated to 100, 300, or 600 μg, or placebo daily (double-blind), or the GLP-1 agonist semaglutide 1 mg once weekly (open-label).

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

Aims: To determine the optimal dose(s) of once-monthly administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin.

Materials And Methods: In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16-week treatment period included a 4-week titration phase with once-weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once-monthly dose.

Retinal Microcirculation in Type 1 Diabetic Patients With and Without Peripheral Sensory Neuropathy.

In patients with diabetes mellitus (DM), early retinal microvascular alterations can be observed even before the clinical diagnosis of diabetic retinopathy. This study aimed to investigate morphological and functional changes in retinal microvascular blood flow in type 1 diabetic patients with and without peripheral neuropathy (PNP) as compared to nondiabetic controls. Retinal microvascular blood flow (RBF) was assessed using scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter, Heidelberg Engineering, Germany) before and after stimulation with flicker light.

Blood glucose meters employing dynamic electrochemistry are stable against hematocrit interference in a laboratory setting.

Background: Hematocrit (HCT) is known to be a confounding factor that interferes with many blood glucose (BG) measurement technologies, resulting in wrong readings. Dynamic electrochemistry has been identified as one possible way to correct for these potential deviations. The purpose of this laboratory investigation was to assess the HCT stability of four BG meters known to employ dynamic electrochemistry (BGStar and iBGStar, Sanofi; Wavesense Jazz, AgaMatrix; Wellion Linus, MedTrust) in comparison with three other devices (GlucoDock, Medisana; OneTouch Verio Pro, LifeScan; FreeStyle Freedom InsuLinx, Abbott-Medisense).

Evaluation of the effects of insufficient blood volume samples on the performance of blood glucose self-test meters.

Background: Accuracy of blood glucose readings is (among other things) dependent on the test strip being completely filled with sufficient sample volume. The devices are supposed to display an error message in case of incomplete filling. This laboratory study was performed to test the performance of 31 commercially available devices in case of incomplete strip filling.

Technical aspects of the Parkes error grid.

Background: The Parkes error grid, which was developed in 1994, presented performance zones for blood glucose (BG) monitors with borders that were not mathematically specified at the time the grid was published.

Methods: In this article, we (1) review the history of the Parkes error grid, (2) present the never-before-published exact coordinates and specifications of the grid so that others may produce an exact replica of the original grid, and (3) discuss our suggestions how this metric should be applied.

Results: The new ISO15197:2013 guideline for system accuracy assessment of BG meters for patient self-measurement incorporates use of this metric for defining acceptable accuracy of BG monitors.

The precision study: examining the inter- and intra-assay variability of replicate measurements of BGStar, iBGStar and 12 other blood glucose monitors.

Objective: Self-monitoring of blood glucose is a key element in diabetes management. Accurate and precise performance of blood glucose monitors (BGMs) ensures that valid values are obtained to guide treatment decisions by patients and physicians. BGStar and iBGStar are hand-held BGMs that use dynamic electrochemistry to correct for potential interferences and thereby minimize system errors.

Bariatric surgery in adolescents and young adults--safety and effectiveness in a cohort of 345 patients.

Objective: To examine the safety and effectiveness of adolescent bariatric surgery and to improve treatment recommendations for this age group.

Design: Prospective longitudinal registry. Since January 2005, patients undergoing bariatric surgery in Germany are enlisted in an online registry called 'study for quality assurance in obesity surgeries'.

Hematocrit interference of blood glucose meters for patient self-measurement.

Background: Abnormal hematocrit levels may interfere with glucose readings of patient self-assessment blood glucose (BG) meters. The aim of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of BG meters applying different measurement technologies.

Methods: Venous heparinized blood was manipulated to contain three different BG concentrations (50-90, 120-180, and 280-350 mg/dl) and five different hematocrit levels (25%, 35%, 45%, 55%, and 65%).

Determination of hematocrit interference in blood samples derived from patients with different blood glucose concentrations.

Background: We performed a blood glucose meter hematocrit (HCT) interference test with lower sample manipulation requirements by using blood samples from patients with different blood glucose (BG) levels.

Methods: Blood from five patients with different BG levels (2.8, 5.

Variability of blood glucose meters for patient self-testing: analysis of the article by Brazg and coauthors.

The article by Brzag and coauthors in this issue of Journal of Diabetes Science and Technology reports a competitive accuracy performance study for a branded meter in comparison with six low-cost meters currently available in the United States. It highlights several important topics: (1) the need for more stringent post-marketing requirements for blood glucose meters after launch and (2) low-cost meters use older technologies and their manufacturers do not usually seriously invest in new technology or constant quality assurance efforts. This may explain the study results, which show superior performance of the branded meter.

Effect of vildagliptin compared to glimepiride on postprandial proinsulin processing in the β cell of patients with type 2 diabetes mellitus.

This study compared the effect of Glimepiride versus Vildagliptin on β-cell function and the release of intact proinsulin (PI) in patients with type 2 diabetes mellitus. Patients on metformin monotherapy were randomized to add on treatment with Vildagliptin or Glimepiride. A standardized test meal was given at baseline, after 12 and 24 weeks of treatment.

Association of sulphonylurea treatment with all-cause and cardiovascular mortality: a systematic review and meta-analysis of observational studies.

We conducted a meta-analysis of cohort and case-control studies to evaluate all-cause and cardiovascular (CV) mortality of patients with type 2 diabetes mellitus (T2DM) who received sulphonylurea (SU) treatment, when compared to any other diabetes treatment. Only studies reporting raw data on mortality during SU treatment were included. Data were combined using random-effects (RE) models.

Clinical overview of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with Type 2 diabetes mellitus.

Linagliptin is a pharmacologically unique, orally active, once-daily dipeptidyl peptidase-4 inhibitor indicated for the treatment of hyperglycemia in patients with Type 2 diabetes mellitus. Compared with other dipeptidyl peptidase-4 inhibitors, linagliptin has a favorable pharmacokinetic profile with a primarily nonrenal route of elimination that avoids the need for dose adjustment in patients with renal impairment. When administered as monotherapy or in combination with other antihyperglycemic drugs, linagliptin treatment leads to clinically meaningful reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose levels.

Development and validation of a rapid and reliable method for TPMT genotyping using real-time PCR.

Background: It is widely accepted that many medications exhibit inter-individual variability in their efficacy and toxicity due to polymorphisms in genes encoding drug-metabolising enzymes. One of the most often cited examples in this context is thiopurine S-methyltransferase (TPMT) polymorphism. TPMT is a phase 2 detoxification enzyme that catalyzes the S-methylation of thiopurine drugs such as thioguanine and 6-mercaptopurine.

Comparison of patient preference for two insulin injection pen devices in relation to patient dexterity skills.

Background: Impaired dexterity has been reported to be prevalent in diabetes patients independent from the existence of diabetic neuropathy. This study was performed to investigate the impact of dexterity impairment on patient preference for two insulin pen injection devices (InnoLet and FlexTouch).

Methods: Ninety patients [54 male/36 female; age (mean ± standard deviation), 62 ± 8 years; disease duration, 18 ± 11 years; hemoglobin A1c, 7.

Patient device assessment evaluation of two insulin injection devices in a mixed cohort of insulin-treated patients with type 1 or type 2 diabetes mellitus.

Objective: FT (FlexTouch*) is a new disposable insulin injection pen device for use in insulin-treated patients with diabetes mellitus. The aim of this study was to evaluate patient perception of FT versus IL (InnoLet†) with respect to the ease of use and patient preference in a mixed patient cohort with different kinds and degrees of visual or dexterity impairments.

Methods: Ninety patients were included into this investigation (54 male/36 female, age [mean ± SD]: 62 ± 8 yrs, disease duration: 18 ± 11 yrs, HbA1c: 7.

Cardiovascular benefits of GLP-1-based herapies in patients with diabetes mellitus type 2: effects on endothelial and vascular dysfunction beyond glycemic control.

Type 2 diabetes mellitus (T2DM) is a progressive multisystemic disease accompanied by vascular dysfunction and a tremendous increase in cardiovascular mortality. Numerous adipose-tissue-derived factors and beta cell dysfunction contribute to the increased cardiovascular risk in patients with T2DM. Nowadays, numerous pharmacological interventions are available to lower blood glucose levels in patients with type 2 diabetes.

Clinical assessment of the accuracy of blood glucose measurement devices.

Objectives: Blood glucose meters for patient self-measurement need to comply with the accuracy standards of the ISO 15197 guideline. We investigated the accuracy of the two new blood glucose meters BG*Star and iBG*Star (Sanofi-Aventis) in comparison to four other competitive devices (Accu-Chek Aviva, Roche Diagnostics; FreeStyle Freedom Lite, Abbott Medisense; Contour, Bayer; OneTouch Ultra 2, Lifescan) at different blood glucose ranges in a clinical setting with healthy subjects and patients with type 1 and type 2 diabetes. BGStar and iBGStar are employ dynamic electrochemistry, which is supposed to result in highly accurate results.

Pilot study for the evaluation of morphological and functional changes in retinal blood flow in patients with insulin resistance and/or type 2 diabetes mellitus.

Background: The aim of this study was to investigate early morphological and functional pathology in the retinal micro-circulation in patients with insulin resistance and/or type 2 diabetes mellitus (T2DM).

Methods: Fifty-four subjects, without features of retinopathy under ophthalmological investigation, were recruited for study participation and were classified into three study groups according to their metabolic staging: (1) Group C comprised nondiabetic, insulin-sensitive subjects with a BMI <28 kg/m(2); (2) Group IR comprised nondiabetic, insulin-resistant, obese subjects with a BMI ≥28 kg/m(2); and (3) Group DM comprised patients with manifested T2DM. Retinal microvascular blood flow was assessed using scanning laser doppler flowmetry (Heidelberg Retina Flowmeter) before and after flicker light stimulation (10 Hz; Photo Stimulater 750).

Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function.

Aims: The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy.

Methods: Forty-four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA(1c) < 53 mmol/mol (7.

Linagliptin, a dipeptidyl peptidase-4 inhibitor with a unique pharmacological profile, and efficacy in a broad range of patients with type 2 diabetes.

Introduction: Increasing population age, obesity and physical inactivity mean that type 2 diabetes mellitus (T2DM) is increasingly common. Current treatments may be limited by adverse events, drug-drug interactions or contraindication/need for dose adjustment in patients with renal impairment.

Areas Covered: This paper reviews studies that evaluate the pharmacokinetics, pharmacodynamics and clinical efficacy and safety of linagliptin , a dipeptidyl peptidase-4 (DPP-4) inhibitor, recently approved in the US, Japan and Europe for the treatment of T2DM.

Self-assessment and objective determination of dexterity in patients with type 1 or type 2 diabetes mellitus.

Objective: Insulin-treated patients perform complex treatment activities during daily routine, such as blood glucose measurements and insulin injections. We aimed to identify suitable dexterity and cognitive function tests for diabetes patients, and to compare the patient self-assessment of their dexterity skills with the test results (Jebsen-Taylor hand function test, (JHFT), motoric performance test (MLS), number connection test).

Method: We enrolled 90 diabetes patients (36 females, 54 males): 15 type 1 with clinically suspected dexterity impairment (A: age: 60 ± 9 years), 30 type 2 with clinically suspected dexterity impairment (B: 61 ± 10 years), 30 type 1 or type 2 patients with visual impairment (C: 64 ± 6 years), and 15 type 1 or type 2 patients without obvious impairment (control group: D: 64 ± 5 years).

Dynamic electrochemistry corrects for hematocrit interference on blood glucose determinations with patient self-measurement devices.

Background: It has been demonstrated that dynamic electrochemistry can be used to correct blood glucose measurement results for potentially interfering conditions, such as humidity, hematocrit (HCT) variations, and ascorbic acid. The purpose of this laboratory investigation was to assess the potential influence of hematocrit variations on a variety of blood glucose meters applying different measurement technologies.

Methods: Venous heparinized whole blood was drawn, immediately aliquoted, and manipulated to contain three different blood glucose concentrations (80, 155, and 310 mg/dl) and five different hematocrit levels (25%, 37%, 45%, 52%, and 60%).

Effect of pioglitazone and ramipril on biomarkers of low-grade inflammation and vascular function in nondiabetic patients with increased cardiovascular risk and an activated inflammation: results from the PIOace study.

Aims: This study investigated the effects of pioglitazone (PIO), ramipril (RAM), or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive patients with increased cardiovascular risk.

Methods And Results: Patients enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72 male, 77 female, aged 60 ± 9 years, body mass index 30.4 ± 4.