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Bergedorf, Germany

Ratner R.,MedStar Research Institute | Nauck M.,Diabeteszentrum | Kapitza C.,Profil Institute fur Stoffwechselforschung GmbH | Asnaghi V.,Hoffmann-La Roche | And 2 more authors.
Diabetic Medicine | Year: 2010

Aims The study objective was to investigate the safety and tolerability of up-titration to high doses of taspoglutide, a once-weekly human glucagon-like peptide-1 analogue, in subjects with Type 2 diabetes inadequately controlled on metformin alone. Methods In this double-blind phase II trial, subjects were randomized to placebo or taspoglutide (20 mg; three separate groups) administered once weekly by subcutaneous injection for 4 weeks. This was followed by dose maintenance at 20 mg, or titration to 30 mg (20/30) or 40 mg (20/40) once weekly with matched placebo for an additional 4 weeks. Subjects were monitored for adverse events (AEs) throughout the study and 4-week follow-up. Results One hundred and twenty-nine subjects were randomized and treated [mean age 57 years, mean baseline glycated haemoglobin (HbA 1c), 7.9%]. The most frequently reported AEs were nausea and vomiting. The number of patients reporting gastrointestinal AEs did not increase following titration to higher doses of taspoglutide or when continuing the initial 20 mg regimen. Three subjects were withdrawn from the study as a result of gastrointestinal AEs (one before and two after titration to higher doses). Although not designed to investigate efficacy, improvement in glycaemic control was observed in all active arms of the study. The proportion of subjects achieving HbA1c < 7.0% after 8 weeks of treatment was 72, 53 and 70% in the 20/20-, 20/30- and 20/40-mg arms, respectively, vs. 19% for placebo. Conclusions Taspoglutide was safe, well tolerated at high doses and efficacious for lowering HbA1c. Up-titration of dose was not associated with a worsening AE profile. © 2010 Diabetes UK.

Buse J.B.,University of North Carolina at Chapel Hill | Garber A.,Baylor College of Medicine | Rosenstock J.,Dallas Diabetes and Endocrine Center at Medical City | Schmidt W.E.,Ruhr University Bochum | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Therapeutic proteins/peptides can produce immunogenic responses that may increase the risk of adverse events or reduce efficacy. Objective: The objectives were to measure and characterize antibody formation to liraglutide, a glucagon-like peptide-1 receptor agonist, to investigate the impact on glycemic control and safety, and to compare it with exenatide, an agent in the same class. Design: Antibody data were collected during six Liraglutide Effect and Action in Diabetes (LEAD) trials (26-104 wk duration). Setting: Samples for determination of antibody formation were collected at LEAD trial sites and analyzed at central laboratories. Participants: Antibodies were measured in LEAD trial participants with type 2 diabetes. Interventions: Interventions included once-daily liraglutide (1.2 or 1.8 mg) or twice-daily exenatide (10 μg). Main Outcome Measures: The main outcome measures included the proportion of patients positive for anti-liraglutide or anti-exenatide antibodies, a glucagon-like peptide-1 cross-reacting effect, and an in vitro liraglutide- or exenatide-neutralizing effect. Change in glycosylated hemoglobin A1c (HbA1c) by antibody status and magnitude [negative, positive (high or low level)]. Results: After 26 wk, 32 of 369 (8.7%) and 49 of 587 (8.3%) patients had low-level antibodies to liraglutide 1.2 and 1.8 mg, respectively [mean 3.3% antibody-bound radioactivity out of total radioactivity (%B/T), range 1.6-10.7%B/T], which did not attenuate glycemic efficacy (HbA1c reductions 1.1-1.3% in antibody-positive vs. 1.2% in antibody-negative patients). In LEAD-6, 113 of 185 extension patients (61%) had anti-exenatide antibodies at wk 26 (range 2.4-60.2%B/T). High levels of anti-exenatide antibodies were correlated with significantly smaller HbA1c reductions (P = 0.0022). After switching from exenatide to liraglutide, anti-exenatide antibodies did not compromise a further glycemic response to liraglutide (additional 0.4% HbA1c reduction). Conclusions: Liraglutide was less immunogenic than exenatide; the frequency and levels of anti-liraglutide antibodies were low and did not impact glycemic efficacy or safety. Copyright © 2011 by The Endocrine Society.

Jecht M.,Gemeinschaftskrankenhaus Havelhohe | Hochlenert D.,Centrum fur Diabetologie | Engels G.,Chirurgische Praxis am Bayenthalgurtel | Morbach S.,Abteilung fur Diabetologie und Angiologie | And 2 more authors.
Diabetologe | Year: 2015

Background: Diabetic foot syndrome (DFS) is a lifelong complication of diabetes with active and inactive phases. The care situation in Germany is of high structural and process quality during the past 10 years due to certification requirements and selective contracts. A registry with a large number of structured and purposefully collected data is lacking in Germany. Objectives: The goal is the characterisation of patients who are treated in specialised care facilities with DFS and are documented in the DFS registry on the basis of selective contracts. Materials and methods: Data of the DFS registry were analysed from January 2005 until September 2014. Results: In all, 102 facilities documented 57,847 cases (59 % men) in 25,038 patients with DFS (14,041 men and 10,997 women). Women with DFS are on average 71.8 years old, men 67.5 years. Women predominate in the age classes from 75–84 years and those above. Peripheral arterial disease (PAD) had been diagnosed in 50 % of the males and 40 % of the females above the age of 75. In women older than 85 years, 10 % have extreme care dependency (level 3) or live in a nursing home. Renal replacement therapy is documented in 2.5 % of the cases. In addition, 955 cases describe active Charcot arthropathy (1.6 % of all cases and 3.4 % of the active DFS cases). These patients are 7 years younger on average. Discussion: The DFS registry is to our knowledge the largest collection of structured and intentionally documented data worldwide. This enables the longitudinal course of the disease by individual phases or over numerous phases to be analysed. Thereby one finds gender- and age-related differences concerning the start of treatment, the presence of PAD, the need for nursing care, renal replacement therapy, and Charcot arthropathy. © 2015, Springer-Verlag Berlin Heidelberg.

Gastaldelli A.,National Research Council Italy | Nauck M.A.,Diabeteszentrum | Balena R.,Hoffmann-La Roche | Balena R.,Eli Lilly and Company
Metabolism: Clinical and Experimental | Year: 2013

Objective Loss of pancreatic function is pivotal to the deterioration of fasting and postprandial glycemic control in type 2 diabetes (T2D). We evaluated the effects of a long-acting, human glucagon-like peptide-1 analog, taspoglutide, added to metformin, on pancreatic function and peripheral insulin sensitivity. Materials/methods We studied 80 T2D patients inadequately controlled [glycosylated hemoglobin (HbA1c), 7.0%-9.5%] receiving stable metformin for ≥ 12 weeks. They were a subset of participants to a phase 2 trial that received also a 240-min mixed-meal tolerance test (MTT) at baseline and study end. Patients received once weekly (QW) sc injection of taspoglutide 5, 10, or 20 mg (n = 21, 19, or 19), or placebo (n = 21), plus metformin, for 8 weeks. We measured postprandial plasma glucose (PPG) and insulin profiles, insulin secretion rate (ISR), oral glucose insulin sensitivity (OGIS) index; β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios, and insulin sensitivity-to-insulin resistance (or disposition) index. Results After 8 weeks of treatment, taspoglutide 5, 10, and 20 mg QW doses vs. placebo improved mean PPG0-240 min (relative change from baseline: - 22.1%, - 25.9%, and - 22.9% vs. - 8.1%; P < 0.005) and mean postprandial ISR0-240 min (+ 14%, + 18%, and + 23% vs. + 1%; P < 0.005 vs dose). Taspoglutide at 20 mg QW dose also resulted in improvements from baseline in OGIS, β-cell glucose sensitivity, glucagon/glucose and insulin/glucagon ratios and the disposition index during the MTT. Conclusion Taspoglutide QW significantly improved pancreatic function in patients with T2D treated with metformin. © 2013 Elsevier Inc.

Introduction: The word "compliance" describes the following of behavioural instructions from doctors. Most often these instructions apply to more or less intensive lifestyle changes for the patient. Discussion: Attempts to change the lifestyle of patients have been, on the whole, unsuccessful. Non-compliance results in poor treatment outcomes. This leads to various reactions on the part of the therapist from frustration to aggression. The expression "noncompliant" often has negative connotations and implies that the patient has such a thing as a free will or - assuming he has a free will - a lack of will to behave in a healthy way. This problem complex will be described with regard to the treatment of chronic wounds. © Schattauer 2013.

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