Profil Mainz

Mainz, Germany

Profil Mainz

Mainz, Germany
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Pfutzner A.,IKFE Services Institute of Clinical Research and Development | Hermanns N.,FIDAM Institute for Diabetes Research | Funke K.,IKFE Potsdam | Forst T.,Profil Mainz | And 4 more authors.
Current Medical Research and Opinion | Year: 2014

Background: The primary objective of this prospective controlled study was to investigate the impact of standardized injection-site warming on prandial rapid acting insulin dose and glycemic control when studied under real-world conditions. Methods: All 145 participating patients (51 female, 94 male, 13 type 1 and 132 type 2 patients, age: 61.6±8.4yrs, HbA1c: 7.19±0.50%) were treated with intensive insulin glargine and short-acting insulin analog therapy. After a 4week treatment optimization run-in period, patients were randomized to continue therapy for three months without (control) or with a local injection-site warming device (InsuPad*). Observation parameters included HbA1c, insulin dose, frequency of hypoglycemia, body weight and adverse events. Results: HbA1c improved in both arms until study end (control group: 6.3±0.5%; injection-site warming device: 6.3±0.5%; both p<0.001 vs. baseline). To achieve this good control, patients in the control group needed to increase the daily prandial insulin dose by 8.1% (from 66±31U to 71±38U, p<0.05) with stable basal insulin requirements. Patients who used the injection-site warming device required less prandial insulin (70±43U to 55±34U; -19%, p<0.001) and slightly more basal insulin (+3.9%). Total daily insulin dose increased in the control group (+3.7%) and decreased with warming device use (-8.6%, p<0.001). The number of hypoglycemic events (<63mg/dL) during the observation period was higher in the control group (6.2±9.9/patient vs. injection-site warming device: 3.3±4.8/patient, p<0.05). Main study limitations can be seen in the open label design reliability of the collected dose information and the very obese patient cohort. Conclusion: When treating obese patients to target with insulin therapy, use of an injection-site warming device for 3months resulted in a lower frequency of hypoglycemic events and a reduction in prandial insulin analog requirements. If these results are confirmed in other patient populations, an injection-site warming device may be useful in achieving treatment targets with a safer and more efficient basal bolus therapy in insulin-treated patients with type 1 and type 2 diabetes. © 2014 All rights reserved.


Forst T.,Profil Mainz | Forst T.,Johannes Gutenberg University Mainz | Guthrie R.,Ohio State University | Goldenberg R.,LMC Diabetes & Endocrinology | And 4 more authors.
Diabetes, Obesity and Metabolism | Year: 2014

Aim: The efficacy and safety of canagliflozin, a sodium glucose co-transporter 2 inhibitor, was evaluated in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and pioglitazone. Methods: In this randomized, double-blind, phase 3 study, patients (N=342) received canagliflozin 100 or 300mg during a 26-week, placebo-controlled, core period and a 26-week, active-controlled extension in which placebo-treated patients were switched to sitagliptin 100mg. Efficacy comparisons for canagliflozin versus placebo at week 26 are reported, with no comparisons versus sitagliptin at week 52 (sitagliptin used to maintain double-blind and control for safety). Safety data are reported for canagliflozin and placebo/sitagliptin. Results: Canagliflozin 100 and 300mg significantly lowered haemoglobin A1c (HbA1c) compared with placebo at week 26 (-0.89%, -1.03% and -0.26%; p < 0.001); reductions with canagliflozin 100 and 300mg were maintained at week 52 (-0.92% and -1.03%). Relative to placebo, both canagliflozin doses significantly reduced body weight (-2.5 and -3.5kg), fasting plasma glucose and systolic blood pressure (BP) at week 26 (p < 0.05 for all), with reductions maintained at week 52. Overall adverse event (AE) incidence over 52 weeks was 69.9, 76.3 and 76.5% with canagliflozin 100 and 300mg and placebo/sitagliptin; AE-related discontinuation and serious AE rates were low. Incidences of genital mycotic infections and AEs related to osmotic diuresis and volume depletion were higher with canagliflozin than placebo/sitagliptin. Conclusion: Canagliflozin improved glycaemic control, reduced body weight and systolic BP, and was generally well tolerated in patients with T2DM on metformin and pioglitazone over 52 weeks. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.


Forst T.,Profil Mainz | Forst T.,Johannes Gutenberg University Mainz | Michelson G.,The Interdisciplinary Center | Diessel S.,Profil Mainz | And 2 more authors.
Journal of Hypertension | Year: 2016

Background: Recent studies suggest vascular benefits of dipeptidylpeptidase IV (DPP-IV) inhibition in patients with diabetes mellitus. Only little is known about potential vascular effects of DPP-IV inhibitors in nondiabetic individuals. The aim of this study was to investigate the effect of DPP-IV inhibition in a nondiabetic hypertensive population. Method: This was a double-blinded, randomized, placebo-controlled, mechanistic study, comparing microvascular effects of the DPP-IV inhibitor linagliptin with placebo in nondiabetic individuals with a history of arterial hypertension. Twenty-one patients received 5 mg linagliptin (5 women; age 67.6 ± 6.0 years; mean ± SD), whereas 22 patients were randomized to placebo (5 women; age 64.8 ± 7.1 years). Results: At baseline, after 6 and 12 weeks, retinal microcirculation and arterial blood pressure profiles were assessed. Moreover, blood samples were taken for the measurement of HbA1c, asymmetric dimethylarginine, C-reactive peptide, cyclic guanosinmonophosphate, transforming growth factor beta (TGF-ß1) and cystatin C. Retinal capillary perfusion increased by 23.7 ± 10.3% (mean ± SEM; P < 0.05), retinal arterial flow by 7.6 ± 0.6 (P < 0.05) and the retinal hyperemic response by 290 ± 263% (P < 0.05) during treatment with linagliptin. No change in retinal blood flow was found in the placebo group. Although blood pressure declined in both groups, a significant decline in TGF-ß1 by 9.3 ± 4.5% (P < 0.05) could only be observed in the linagliptin group. No significant change in other laboratory parameters could be observed in both groups. Conclusion: Our study suggests microvascular and antifibrotic effects of linagliptin in a nondiabetic, hypertensive population. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | Profil Neuss, Johannes Gutenberg University Mainz, MLM Medical Labs and Profil Mainz
Type: | Journal: Diabetes, obesity & metabolism | Year: 2016

The aim of the study was to investigate the effect of sequential treatment escalation with empagliflozin and linagliptin on laboratory markers of alpha- and beta cell function in patients with type 2 diabetes mellitus (T2DM) insufficiently controlled on metformin monotherapy.Forty-four patients with T2DM received 25 mg empagliflozin for a duration of one month in an open-label fashion (treatment period (TP 1). Thereafter, patients were randomised to a double-blind add-on therapy with linagliptin 5 mg or placebo (TP 2) for one additional month. Alpha- and beta cell function were assessed with a standardised liquid meal test (LMT) and an intravenous (iv.) glucose challenge. Efficacy parameters comprised of the area under the curve (AUC) for glucose, insulin, proinsulin and glucagon after the LMT and the assessment of fast- and late-phase insulin release after an intravenous glucose load with a subsequent hyperglycaemic clamp.Empagliflozin reduced fasting and postprandial plasma glucose levels associated with a significant reduction in postprandial insulin levels, and an improvement in the conversion rate of proinsulin (TP 1). Addition of linagliptin during TP 2 further improved postprandial glucose levels most probably due to a marked reduction in postprandial glucagon concentrations (TP 2). The insulin response to an intravenous glucose load increased during treatment with empagliflozin (TP 1), and further improved after the addition of linagliptin (TP 2).After metformin failure, sequential treatment escalation with empagliflozin and linagliptin is an attractive treatment option due to additive effects on postprandial glucose control, most probably mediated by complementary effects on alpha- and beta cell function.


PubMed | Profil Mainz, Li Ka Shing Knowledge Institute and Janssen Research & Development LLC
Type: Clinical Trial, Phase III | Journal: Diabetes & metabolism | Year: 2016

To report changes in liver function tests observed with canagliflozin, a sodium glucose co-transporter 2 inhibitor, across phase 3 studies in patients with type 2 diabetes, and to examine the relationship between changes in liver function tests and the weight loss and glycaemic improvements observed with canagliflozin.Data were pooled from four 26-week, placebo-controlled studies of canagliflozin 100 and 300mg (n=2313) and two 52-week, active-controlled studies of canagliflozin 300mg versus sitagliptin 100mg (n=1488). Analysis of covariance was performed to determine the contribution of changes in body weight and HbA1c to the changes in liver function tests.Reductions in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transferase, and increases in bilirubin were seen with canagliflozin 100 and 300mg versus placebo (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase [both doses]; P<0.001 for alkaline phosphatase and P=0.015 for bilirubin [canagliflozin 300mg only]) at week 26 and with canagliflozin 300mg versus sitagliptin 100mg (nominal P<0.001 for alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase and bilirubin, and P<0.01 for alkaline phosphatase) at week 52. Few patients met predefined limits of change criteria for liver function tests, and none met Hys law criteria. In both populations, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase reductions were fully explained by HbA1c and body weight reductions.Canagliflozin provided improvements in liver function tests versus either placebo or sitagliptin treatments that were fully explained by the combined effects of HbA1c and body weight reductions with canagliflozin.


PubMed | Profil Mainz, Lilly United States LLC., Grunberger Diabetes Institute, Churchill Hospital and Eli Lilly and Company
Type: Clinical Trial, Phase III | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2016

To assess whether early measures of fasting blood glucose predict later glycaemic response with once-weekly dulaglutide in patients with Type 2 diabetes mellitus.Post hoc analyses were conducted separately for two phase 3 studies (AWARD-5 and AWARD-1) in patients assigned to once-weekly dulaglutide. Week 2 fasting blood glucose was used as a predictor variable, and glycaemic treatment response was defined by HbA1c response based on a composite efficacy endpoint. The association between fasting blood glucose and the glycaemic response was analysed using chi-square tests.There was a strong association between fasting blood glucose < 7.9 mmol/l at week 2 and achieving the HbA1c composite efficacy endpoint at week 26 (P < 0.01). Higher fasting blood glucose at week 2, however, did not predict absence of glycaemic response and requires further assessment.Fasting blood glucose measured at 2 weeks may be an early and useful predictor of glycaemic response to once-weekly dulaglutide treatment.


Pfutzner A.,Diabetes Center and Practice | Dissel S.,Profil Mainz | Forkel C.,ClinLogix Europe | Grenningloh M.,ClinLogix Europe | And 3 more authors.
Current Medical Research and Opinion | Year: 2014

Objectives: Use of an injection site modulation device (InsuPad) in intensive insulin treatment reduces frequency of hypoglycemia and prandial insulin requirements by enhancing subcutaneous microcirculation. This meal tolerance test (MTT) investigation was performed as a sub-study during the real-world BARMER study to demonstrate non-inferiority of the reduced insulin doses observed in this study with respect to metabolic control. Methods: The MTT was performed at baseline and after 3 months in insulin treated diabetes patients using the modulation device vs. a control group without device. The dose used for the MTT was individually calculated based on the prandial insulin records from the patient diaries before the test. Blood was drawn for determination of glucose, insulin, C-peptide, proinsulin, triglycerides, free fatty acids, nitrotyrosine, and asymmetric dimethyl-arginine (ADMA) at multiple time-points from 0 to 300 min. A total of 32 patients from one site were included into this MTT study (8 female, 7 type 1 diabetes, age: 49.9 ± 12.5 yrs, HbA1c: 7.2 ± 0.5%). Results: During the BARMER study, mean HbA1c was treated to target (<6.5%) in both groups. The prandial insulin dose decreased in the MTT modulation device group by -17.1%, but remained unchanged in the control group (-0.1%, p < 0.001). No change was seen for the basal insulin dose in both treatment arms. There were no differences between the groups with respect to the postprandial curves for glucose, C-peptide, intact proinsulin, free fatty acids, and triglycerides. Insulin absorption was faster with the modulation device (Tmax: 60 ± 28 min vs. 99± 46 min, p < 0.05). Key limitations are the small patient sample size and impossibility to determine the short-term effects of device use. Conclusions: The results of this meal tolerance sub-study confirm that the observed prandial insulin dose reduction when using the injection site modulation device has no negative impact on postprandial metabolism. © 2014 Informa UK Ltd.


Forst T.,Profil Mainz | Pfutzner A.,Institute for Clinical Research and Development
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: The global prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing and is associated with a high risk of microvascular and macrovascular complications. Although some glucose-lowering therapies are associated with hypoglycemia and weight gain, glucagon-like peptide-1 (GLP-1) receptor agonists represent a significant advance in the treatment of T2DM, as they provide effective glycemic control with a low incidence of hypoglycemia and a beneficial effect on body weight, as well as potential improvements in cardiovascular outcomes. Areas covered: This article evaluates the pharmacological and clinical profile of the once-daily prandial GLP-1 receptor agonist lixisenatide for the treatment of T2DM. Expert opinion: Once-daily prandial lixisenatide has been evaluated in an extensive clinical trials program, in which it was shown to have a favorable safety and tolerability profile, and to effectively improve metabolic control. The unique pharmacological properties of lixisenatide clearly differentiate it from other GLP-1 receptor agonists. As a once-daily agonist with a high affinity for the GLP-1 receptor, lixisenatide improves overall glycemic control, with particularly strong effects on postprandial plasma glucose levels. These attributes encourage the application of lixisenatide in those patients with extensive postprandial glucose excursions, or in combination with other antidiabetic drugs that have prevailing effects on fasting glucose levels. © Informa UK, Ltd.


Forst T.,Profil Mainz | Anastassiadis E.,Profil Mainz | Diessel S.,Profil Mainz | Loffler A.,Profil Mainz | Pfutzner A.,Profil Mainz
Diabetes/metabolism research and reviews | Year: 2014

BACKGROUND: The goal of this study was to investigate the effects of linagliptin compared with glimepiride on alpha and beta cell function and several vascular biomarkers after a standardized test meal.METHODS: Thirty-nine patients on metformin alone (age, 64 ± 7 years; duration of type 2 diabetes mellitus, 7.8 ± 4.5years, 27 male, 12 female; HbA1c , 57.2 ± 6.9 mmol/mol; mean ± SD) were randomized to receive linagliptin 5 mg (n = 19) or glimepiride (n = 20) for a study duration of 12 weeks. Glucagon-like peptide 1, blood glucose, insulin, intact proinsulin, glucagon, plasminogen activator inhibitor-1 (PAI-1), cyclic guanosinmonophosphat and asymetric dimethylarginin levels were measured in the fasting state and postprandial at 30-min intervals for a duration of 5 h. The areas under the curve (AUC0-300 min ) were calculated for group comparisons.RESULTS: HbA1c , fasting and postprandial glucose levels improved in both groups. An increase in postprandial insulin (22595 ± 5984 pmol/L*min), postprandial intact proinsulin (1359 ± 658 pmol/L*min), postprandial glucagon (317 ± 1136 pg/mL*min) and postprandial PAI-1 levels (863 ± 467 ng/mL*min) could be observed during treatment with glimepiride, whereas treatment with linagliptin was associated with a decrease in postprandial insulin (-8007 ± 4204 pmol/L*min), intact proinsulin (-1771 ± 426 pmol/L*min), postprandial glucagon (-1597 ± 1831 pg/mL*min) and PAI-1 levels (-410 ± 276 ng/mL*min).CONCLUSIONS: Despite an improvement in blood glucose control in both groups, linagliptin reduced postprandial insulin, proinsulin, glucagon and PAI-levels. These results indicate an improvement in postprandial alpha and beta cell function, as well as a reduced postprandial vascular risk profile during treatment with linagliptin. Copyright © 2014 John Wiley & Sons, Ltd.


PubMed | Profil Mainz
Type: Journal Article | Journal: Expert opinion on pharmacotherapy | Year: 2013

The global prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing and is associated with a high risk of microvascular and macrovascular complications. Although some glucose-lowering therapies are associated with hypoglycemia and weight gain, glucagon-like peptide-1 (GLP-1) receptor agonists represent a significant advance in the treatment of T2DM, as they provide effective glycemic control with a low incidence of hypoglycemia and a beneficial effect on body weight, as well as potential improvements in cardiovascular outcomes.This article evaluates the pharmacological and clinical profile of the once-daily prandial GLP-1 receptor agonist lixisenatide for the treatment of T2DM.Once-daily prandial lixisenatide has been evaluated in an extensive clinical trials program, in which it was shown to have a favorable safety and tolerability profile, and to effectively improve metabolic control. The unique pharmacological properties of lixisenatide clearly differentiate it from other GLP-1 receptor agonists. As a once-daily agonist with a high affinity for the GLP-1 receptor, lixisenatide improves overall glycemic control, with particularly strong effects on postprandial plasma glucose levels. These attributes encourage the application of lixisenatide in those patients with extensive postprandial glucose excursions, or in combination with other antidiabetic drugs that have prevailing effects on fasting glucose levels.

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