The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Andrea Siebenhofer - One of the best experts on this subject based on the ideXlab platform.
-
ultra Long Acting Insulin analogues versus nph Insulin human isophane Insulin for adults with type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2020Co-Authors: Thomas Semlitsch, Jennifer Engler, Andrea Siebenhofer, Klaus Jeitler, Andrea Berghold, Karl HorvathAbstract:Background Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer Insulin analogues may result in fewer macrovascular and microvascular events. Objectives To compare the effects of Long-term treatment with (ultra-)Long-Acting Insulin analogues (Insulin glargine U100 and U300, Insulin detemir and Insulin degludec) with NPH (neutral protamine Hagedorn) Insulin (human isophane Insulin) in adults with type 2 diabetes mellitus. Search methods For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions. Selection criteria We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)Long-Acting Insulin analogues to NPH in adults with type 2 diabetes mellitus. Data collection and analysis Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses. Main results We identified 24 RCTs. Of these, 16 trials compared Insulin glargine to NPH Insulin and eight trials compared Insulin detemir to NPH Insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to Insulin glargine and 1321 people to Insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing Insulin glargine to NPH Insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing Insulin detemir to NPH Insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, Insulin glargine and Insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH Insulin. Changes in HbA1c were comparable for Long-Acting Insulin analogues and NPH Insulin. Insulin glargine compared to NPH Insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with Insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with Insulin detemir compared to NPH Insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such as death from any cause, diabetes-related complications, health-related quality of life and socioeconomic effects was insufficient or lacking in almost all included trials. For those outcomes for which some data were available, there were no meaningful differences between treatment with glargine or detemir and treatment with NPH. There was no clear difference between Insulin-analogues and NPH Insulin in terms of weight gain. The incidence of adverse events was comparable for people treated with glargine or detemir, and people treated with NPH. We found no trials comparing ultra-Long-Acting Insulin glargine U300 or Insulin degludec with NPH Insulin. Authors' conclusions While the effects on HbA1c were comparable, treatment with Insulin glargine and Insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH Insulin. Treatment with Insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with Insulin detemir instead of NPH Insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a Long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.
-
Long Acting Insulin analogues versus nph Insulin human isophane Insulin for type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2007Co-Authors: Karl Horvath, Klaus Jeitler, Andrea Berghold, Susanne H Ebrahim, Thomas W Gratzer, Johannes Plank, Thomas Kaiser, Thomas R Pieber, Andrea SiebenhoferAbstract:Background Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer Insulin analogues might result in fewer macrovascular and microvascular events. Objectives To assess the effects of Long-term treatment with Long-Acting Insulin analogues (Insulin glargine and Insulin detemir) compared to NPH Insulin in patients with type 2 diabetes mellitus. Search methods Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as Insulin producing companies. Selection criteria Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks. Data collection and analysis Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed. Main results Six studies comparing Insulin glargine to NPH (Neutral Protamine Hagedorn) Insulin and two studies comparing Insulin detemir to NPH Insulin were identified. In these trials, 1715 patients were randomised to Insulin glargine and 578 patients to Insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either Insulin glargine or detemir. No evidence for a beneficial effect of Long-Acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained. Authors' conclusions Our analysis suggests, if at all only a minor clinical benefit of treatment with Long-Acting Insulin analogues for patients with diabetes mellitus type 2 treated with "basal" Insulin regarding symptomatic nocturnal hypoglycaemic events. Until Long-term efficacy and safety data are available, we suggest a cautious approach to therapy with Insulin glargine or detemir.
-
pharmacokinetic and pharmacodynamic properties of Long Acting Insulin analogue nn304 in comparison to nph Insulin in humans
Experimental and Clinical Endocrinology & Diabetes, 2000Co-Authors: Gernot Brunner, Andrea Siebenhofer, S Hirschberger, Gerald Sendlhofer, A Wutte, M Ellmerer, B Sogaard, G J Krejs, Thomas R PieberAbstract:Abstract NN304 is a Long-Acting Insulin analogue that is acylated with a 14-C-fatty acid chain. Protraction of action of this novel Insulin analogue is due not to slow absorption after subcutaneous administration but to reversible binding to albumin. We investigated the pharmacokinetic and pharmacodynamic properties of Insulin analogue NN304 (0.3 and 0.6 U/kg) in comparison to NPH Insulin (0.3 and 0.6 IU/kg) in 10 healthy volunteers performing a randomised, double-blind, cross-over, placebo-controlled glucose clamp study. During the observation period of 24 hours the areas under the Insulin curve for NPH[0.3 IU/kg] vs. NPH[0.6 IU/kg] were 60 vs. 102 nmol min l(-1) (p<0.01) and for Insulin analogue NN304[0.3 U/kg] vs. NN304[0.6 U/kg] 490 vs. 932 nmol min l(-1) (p <0.001), suggesting a clear dose-response relationship for both NPH Insulin and NN304. The amount of disposed glucose (area under the curve of glucose infusion) differed with statistical significance between the five treatments and was highest with NPH[0.6 IU/kg] (2671 mg/kg) and lowest with placebo (265 mg/kg). However, area under the curve of glucose infusion after treatment with NN304 was only 36% (dose of 0.3 U/kg) and 24% (dose of 0.6 U/kg) of that observed with corresponding doses of NPH Insulin. Moreover, increasing dosages of NN304 failed to demonstrate a significant dose-response with regard to the area under the curve of glucose infusion. This study demonstrates that the principle of protracted Insulin action of NN304 by reversible binding to albumin is effective in humans albeit at a much lower rate of glucose utilisation when compared to NPH Insulin. Thus, in contrast to animal studies NN304 and NPH Insulin can not be considered equipotent in humans.
Karl Horvath - One of the best experts on this subject based on the ideXlab platform.
-
ultra Long Acting Insulin analogues versus nph Insulin human isophane Insulin for adults with type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2020Co-Authors: Thomas Semlitsch, Jennifer Engler, Andrea Siebenhofer, Klaus Jeitler, Andrea Berghold, Karl HorvathAbstract:Background Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer Insulin analogues may result in fewer macrovascular and microvascular events. Objectives To compare the effects of Long-term treatment with (ultra-)Long-Acting Insulin analogues (Insulin glargine U100 and U300, Insulin detemir and Insulin degludec) with NPH (neutral protamine Hagedorn) Insulin (human isophane Insulin) in adults with type 2 diabetes mellitus. Search methods For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions. Selection criteria We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)Long-Acting Insulin analogues to NPH in adults with type 2 diabetes mellitus. Data collection and analysis Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses. Main results We identified 24 RCTs. Of these, 16 trials compared Insulin glargine to NPH Insulin and eight trials compared Insulin detemir to NPH Insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to Insulin glargine and 1321 people to Insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing Insulin glargine to NPH Insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing Insulin detemir to NPH Insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, Insulin glargine and Insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH Insulin. Changes in HbA1c were comparable for Long-Acting Insulin analogues and NPH Insulin. Insulin glargine compared to NPH Insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with Insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with Insulin detemir compared to NPH Insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such as death from any cause, diabetes-related complications, health-related quality of life and socioeconomic effects was insufficient or lacking in almost all included trials. For those outcomes for which some data were available, there were no meaningful differences between treatment with glargine or detemir and treatment with NPH. There was no clear difference between Insulin-analogues and NPH Insulin in terms of weight gain. The incidence of adverse events was comparable for people treated with glargine or detemir, and people treated with NPH. We found no trials comparing ultra-Long-Acting Insulin glargine U300 or Insulin degludec with NPH Insulin. Authors' conclusions While the effects on HbA1c were comparable, treatment with Insulin glargine and Insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH Insulin. Treatment with Insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with Insulin detemir instead of NPH Insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a Long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.
-
Long Acting Insulin analogues versus nph Insulin human isophane Insulin for type 2 diabetes mellitus
Cochrane Database of Systematic Reviews, 2007Co-Authors: Karl Horvath, Klaus Jeitler, Andrea Berghold, Susanne H Ebrahim, Thomas W Gratzer, Johannes Plank, Thomas Kaiser, Thomas R Pieber, Andrea SiebenhoferAbstract:Background Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer Insulin analogues might result in fewer macrovascular and microvascular events. Objectives To assess the effects of Long-term treatment with Long-Acting Insulin analogues (Insulin glargine and Insulin detemir) compared to NPH Insulin in patients with type 2 diabetes mellitus. Search methods Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as Insulin producing companies. Selection criteria Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks. Data collection and analysis Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed. Main results Six studies comparing Insulin glargine to NPH (Neutral Protamine Hagedorn) Insulin and two studies comparing Insulin detemir to NPH Insulin were identified. In these trials, 1715 patients were randomised to Insulin glargine and 578 patients to Insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either Insulin glargine or detemir. No evidence for a beneficial effect of Long-Acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained. Authors' conclusions Our analysis suggests, if at all only a minor clinical benefit of treatment with Long-Acting Insulin analogues for patients with diabetes mellitus type 2 treated with "basal" Insulin regarding symptomatic nocturnal hypoglycaemic events. Until Long-term efficacy and safety data are available, we suggest a cautious approach to therapy with Insulin glargine or detemir.
Claudio Cobelli - One of the best experts on this subject based on the ideXlab platform.
-
in silico head to head comparison of Insulin glargine 300 u ml and Insulin degludec 100 u ml in type 1 diabetes
Diabetes Technology & Therapeutics, 2020Co-Authors: Michele Schiavon, Roberto Visentin, Clemens Giegerich, Jochen Sieber, Chiara Dalla Man, Claudio Cobelli, Thomas KlabundeAbstract:Background: Second-generation Long-Acting Insulin glargine 300 U/mL (Gla-300) and degludec 100 U/mL (Deg-100) provide novel basal Insulin therapies for the treatment of type 1 diabetes (T1D). Both ...
-
modeling subcutaneous absorption of Long Acting Insulin glargine in type 1 diabetes
IEEE Transactions on Biomedical Engineering, 2020Co-Authors: Michele Schiavon, Roberto Visentin, Clemens Giegerich, Claudio Cobelli, Thomas Klabunde, Chiara Dalla ManAbstract:Objective: Subcutaneous (sc) administration of Long-Acting Insulin analogs is often employed in multiple daily injection (MDI) therapy of type 1 diabetes (T1D) to cover patient's basal Insulin needs. Among these, Insulin glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) are formulations indicated for once daily sc administration in MDI therapy of T1D. A few semi-mechanistic models of sc absorption of Insulin glargine have been proposed in the literature, but were not quantitatively assessed on a large dataset. The aim of this paper is to propose a model of sc absorption of Insulin glargine able to describe the data and provide precise model parameters estimates with a clear physiological interpretation. Methods: Three candidate models were identified on a total of 47 and 77 Insulin profiles of T1D subjects receiving a single or repeated sc administration of Gla-100 or Gla-300, respectively. Model comparison and selection were performed on the basis of their ability to describe the data and numerical identifiability. Results: The most parsimonious model is linear two-compartment and accounts for the Insulin distribution between the two compartments after sc administration through parameter k . Between the two formulations, we report a lower fraction of Insulin in the first versus second compartment ( k = 86% versus 94% in Gla-100 versus Gla-300, p $k_{sp}= \text{0.0013}$ versus 0.0008 min−1 in Gla-100 versus Gla-300, p $k_{a}= \text{0.0018}$ versus 0.0016 min−1 in Gla-100 versus Gla-300, p = NS), in accordance with the mechanisms of Insulin glargine protraction. Conclusions: The proposed model is able to both accurately describe plasma Insulin data after sc administration and precisely estimate physiologically plausible parameters. Significance: The model can be incorporated in simulation platforms potentially usable for optimizing basal Insulin treatment strategies.
-
incorporating Long Acting Insulin glargine into the uva padova type 1 diabetes simulator for in silico testing of mdi therapies
IEEE Transactions on Biomedical Engineering, 2019Co-Authors: Roberto Visentin, Michele Schiavon, Clemens Giegerich, Chiara Dalla Man, Thomas Klabunde, Claudio CobelliAbstract:Objective: Glargine 100 U/mL (Gla-100) and 300 U/mL (Gla-300) are Long-Acting Insulin analogs providing basal Insulin supply in multiple daily injection (MDI) therapy of type 1 diabetes (T1D). Both Insulins require extensive testing to arrive at the optimal dosing regimen, e.g., timing and amount. Here we aim at a simulation tool for evaluating benefits/risks of different dosing schemes and up-titration rules for both Gla-100 and Gla-300 before clinical testing. Methods: A new pharmacokinetic (PK) model of both Gla-100 and Gla-300 was incorporated into the FDA-accepted University of Virginia/Padova T1D simulator: Specifically, a joint parameter distribution, built from PK parameter estimates, was used to generate individual PK parametrizations for each in silico subject. A virtual trial comparing Gla-100 vs. Gla-300 was performed and assessed against a clinical study to validate the glargine simulator. Results: Like in vivo , in silico both Insulins performed similarly with respect to glucose control: percent time of glucose between [80–140] mg/dL with Gla-100 vs. Gla-300 (primary endpoint) were 41.5 ± 1.1% vs. 39.0 ± 1.2% ( P = 0.11) in silico , 31.0 ± 1.6% vs. 31.8 ± 1.5% ( P = 0.73) in vivo . Conclusions: The glargine simulator reproduced the main findings of the clinical trial, proving its validity for testing MDI therapies. Significance: In silico testing of MDI therapies can help designing clinical trials. Due to the more standardized settings in silico (e.g., standardized meals and strict adherence to titration rule), any potential treatment effect is reaching statistical significance in simulation vs. clinical trial.
-
Long Acting Insulin in diabetes therapy in silico clinical trials with the uva padova type 1 diabetes simulator
International Conference of the IEEE Engineering in Medicine and Biology Society, 2018Co-Authors: Roberto Visentin, Michele Schiavon, Clemens Giegerich, Chiara Dalla Man, Thomas Klabunde, Claudio CobelliAbstract:The University of Virginia /Padova Type 1 Diabetes (TID) simulator has been widely used for testing artificial pancreas controllers, and, recently, novel Insulin formulations and glucose sensors. However, a module describing the pharmacokinetics of the new Long-Acting Insulin analogues is not available. The aim of this contribution is to reproduce multiple daily Insulin injection (MDI) therapy, with Insulin glargine 100 U/mL (Gla-100) as basal Insulin, using the TID simulator. This was achieved by developing a model of Gla-100 and by incorporating it into the simulator. The methodology described here can be extended to other Insulins, allowing an extensive in silico testing of different Long-Acting Insulin analogues under various settings before starting human trials.
Edoardo Mannucci - One of the best experts on this subject based on the ideXlab platform.
-
Long Acting Insulin analogues vs nph human Insulin in type 1 diabetes a meta analysis
Diabetes Obesity and Metabolism, 2009Co-Authors: Matteo Monami, Niccolo Marchionni, Edoardo MannucciAbstract:Aim: Basal Insulin in type 1 diabetes can be provided using either NPH (Neutral Protamine Hagedorn) human Insulin or Long-Acting Insulin analogues, which are supposed to warrant a better metabolic control with reduced hypoglycaemic risk. Aim of this meta-analysis is the assessment of differences with respect to HbA1c (Glycated hemoglobin), incidence of hypoglycaemia, and weight gain, between NPH human Insulin and each Long-Acting analogue. Methods: Of 285 randomized controlled trials with a duration > 12 weeks comparing Long-Acting Insulin analogues (detemir or glargine) with NPH Insulin in type 1 diabetic patients identified through Medline search and searches on www.clinicaltrials.gov, 20 met eligibility criteria (enrolling 3693 and 2485 in the Long-Acting analogues and NPH group respectively). Data on HbA1c and body mass index at endpoint, and incidence of any, nocturnal and severe hypoglycaemia, were extracted and meta-analysed. Results: Long-Acting analogues had a small, but significant effect on HbA1c [-0.07 (−0.13; −0.01)%; p = 0.026], in comparison with NPH human Insulin. When analysing the effect of Long-Acting analogues on body weight, detemir was associated with a significantly smaller weight gain than human Insulin [by 0.26 (0.06;0.47) kg/m2; p = 0.012]. Long-Acting analogues were associated with a reduced risk for nocturnal and severe hypoglycaemia [OR (Odd Ratio, 95% Confidence Intervals) 0.69 (0.55; 0.86), and OR 0.73 (0.60; 0.89) respectively; all p < 0.01]. Conclusions: The switch from NPH to Long-Acting analogues as basal Insulin replacement in type 1 diabetic patients had a small effect on HbA1c, and also reduced the risk of nocturnal and severe hypoglycaemia.
-
Long Acting Insulin analogues versus nph human Insulin in type 2 diabetes a meta analysis
Diabetes Research and Clinical Practice, 2008Co-Authors: Matteo Monami, Niccolo Marchionni, Edoardo MannucciAbstract:Abstract Background Long-Acting Insulin analogues, in comparison with NPH Insulin, should warrant a greater reproducibility of absorption after subcutaneous injection, providing better metabolic control with reduced hypoglycaemic risk. Aim of the present meta-analysis is the assessment of differences with respect to HbA1c, incidence of hypoglycaemia, weight gain, between NPH human Insulin and each Long-Acting analogue. Methods All randomized controlled trials (RCTs) with a duration >12 weeks comparing Long-Acting Insulin analogues (detemir or glargine) with NPH Insulin in type 2 diabetic patients were retrieved; data on HbA1c and BMI at endpoint, and incidence of any, symptomatic, nocturnal, and severe hypoglycaemia, were extracted and meta-analysed. Results A total of 14 RCTs was retrieved and included in the analysis. Long-Acting analogues did not produce any significant improvement of HbA1c, in comparison with NPH human Insulin. When trials with different analogues were analysed separately, NPH showed a significant superiority (by 0.1%) over detemir, but not over glargine. When analysing the effect of Long-Acting analogues on body weight, detemir, but not glargine, was associated with a significantly smaller weight gain than human Insulin Both analogues were associated with a reduced risk for nocturnal and symptomatic hypoglycaemia (OR: 0.46[0.38–0.55] and 0.69[0.60–0.80]; all p Conclusions Long-Acting Insulin analogues in type 2 diabetic patients does not seem to provide a better glycemic control in comparison with NPH Insulin, whereas it reduces the risk of nocturnal and symptomatic hypoglycemia. Detemir, but not glargine, could be associated with smaller weight gain than NPH Insulin.
Sharon E Straus - One of the best experts on this subject based on the ideXlab platform.
-
safety effectiveness and cost of Long Acting versus intermediate Acting Insulin for type 1 diabetes protocol for a systematic review and network meta analysis
Systematic Reviews, 2013Co-Authors: Andrea C Tricco, Huda M Ashoor, Charlene Soobiah, Brenda R Hemmelgarn, David Moher, Brian Hutton, Sumit R Majumdar, Sharon E StrausAbstract:Background Type 1 diabetes mellitus (T1DM) causes progressive destruction of pancreatic beta cells leading to absolute Insulin deficiency. Treatment of T1DM requires Insulin, and some evidence suggests that Longer Acting Insulin analogues might have a higher effectiveness and greater safety profile compared to intermediate-Acting Insulin. Our objective is to evaluate the comparative effectiveness, safety, and cost of Long-Acting Insulin versus intermediate-Acting Insulin through a systematic review and network meta-analysis.
