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Thomas R Pieber - One of the best experts on this subject based on the ideXlab platform.

  • Short Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • The Cochrane Library - Short‐Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • The Cochrane Library - Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • systematic review and meta analysis of Short Acting Insulin analogues in patients with diabetes mellitus
    JAMA Internal Medicine, 2005
    Co-Authors: Johannes Plank, Andrea Siebenhofer, Andrea Berghold, Klaus Jeitler, Karl Horvath, Peter Mrak, Thomas R Pieber
    Abstract:

    Background This article compares the effect of treatment with Short-Acting Insulin (SAI) analogues vs regular Insulin on glycemic control, hypoglycemic episodes, quality of life, and diabetes-specific complications. Methods Electronic searches (Cochrane Library, MEDLINE, and EMBASE) and additional searching (pharmaceutical companies, experts, approval agencies, abstracts of diabetology meetings) were performed. Two reviewers independently screened randomized controlled trials to determine inclusion. Results Forty-two randomized controlled trials that assessed the effect of SAI analogues vs regular Insulin in 7933 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus were identified. The weighted mean difference between hemoglobin A 1c values obtained using SAI analogues and regular Insulin was −0.12% (95% confidence interval [CI], −0.17% to −0.07%) for adult patients with type 1 diabetes mellitus and −0.02% (95% CI, −0.10% to 0.07%) for patients with type 2 diabetes mellitus. The standardized mean difference for overall hypoglycemia (episodes per patient per month) was −0.05 (95% CI, −0.22 to 0.11) and −0.04 (95% CI, −0.12 to 0.04) comparing SAI analogues with regular Insulin in adult patients with type 1 and type 2 diabetes mellitus, respectively. No differences between treatments were observed in children with type 1 diabetes, pregnant women with type 1 diabetes mellitus, and women with gestational diabetes. Concerning quality of life, improvement was observed only in open-label studies in patients with type 1 diabetes mellitus. No differences were seen in a double-blinded study of patients with type 1 or in the studies of patients with type 2 diabetes mellitus. Conclusion Our analysis suggests only a minor benefit to hemoglobin A 1c values in adult patients with type 1 diabetes mellitus but no benefit in the remaining population with type 2 or gestational diabetes from SAI analogue treatment.

Andrea Siebenhofer - One of the best experts on this subject based on the ideXlab platform.

  • Short-Acting Insulin analogues versus regular human Insulin for adult, non-pregnant persons with type 2 diabetes mellitus.
    Cochrane Database of Systematic Reviews, 2018
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    The use of Short-Acting Insulin analogues (Insulin lispro, Insulin aspart, Insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates. To assess the effects of Short-Acting Insulin analogues compared to regular human Insulin in adult, non-pregnant people with type 2 diabetes mellitus. For this update we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication. We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues to regular human Insulin in the treatment of people with type 2 diabetes, who were not pregnant. Two review authors independently extracted data and assessed the risk of bias. We assessed dichotomous outcomes by risk ratios (RR), and Peto odds ratios (POR), with 95% confidence intervals (CI). We assessed continuous outcomes by mean differences (MD) with 95% CI. We assessed trials for certainty of the evidence using the GRADE approach. We identified 10 trials that fulfilled the inclusion criteria, randomising 2751 participants; 1388 participants were randomised to receive Insulin analogues and 1363 participants to receive regular human Insulin. The duration of the intervention ranged from 24 to 104 weeks, with a mean of about 41 weeks. The trial populations showed diversity in disease duration, and inclusion and exclusion criteria. None of the trials were blinded, so the risk of performance bias and detection bias, especially for subjective outcomes, such as hypoglycaemia, was high in nine of 10 trials from which we extracted data. Several trials showed inconsistencies in the reporting of methods and results.None of the included trials defined all-cause mortality as a primary outcome. Six trials provided Information on the number of participants who died during the trial, with five deaths out of 1272 participants (0.4%) in the Insulin analogue groups and three deaths out of 1247 participants (0.2%) in the regular human Insulin groups (Peto OR 1.66, 95% CI 0.41 to 6.64; P = 0.48; moderate-certainty evidence). Six trials, with 2509 participants, assessed severe hypoglycaemia differently, therefore, we could not summarise the results with a meta-analysis. Overall, the incidence of severe hypoglycaemic events was low, and none of the trials showed a clear difference between the two intervention arms (low-certainty evidence).The MD in glycosylated haemoglobin A1c (HbA1c) change was -0.03% (95% CI -0.16 to 0.09; P = 0.60; 9 trials, 2608 participants; low-certainty evidence). The 95% prediction ranged between -0.31% and 0.25%. The MD in the overall number of non-severe hypoglycaemic episodes per participant per month was 0.08 events (95% CI 0.00 to 0.16; P = 0.05; 7 trials, 2667 participants; very low-certainty evidence). The 95% prediction interval ranged between -0.03 and 0.19 events per participant per month. The results provided for nocturnal hypoglycaemic episodes were of questionable validity. Overall, there was no clear difference between the two Short-Acting Insulin analogues and regular human Insulin. Two trials assessed health-related quality of life and treatment satisfaction, but we considered the results for both outcomes to be unreliable (very low-certainty evidence).No trial was designed to investigate possible long term effects (all-cause mortality, microvascular or macrovascular complications of diabetes), especially in participants with diabetes-related complications. No trial reported on socioeconomic effects. Our analysis found no clear benefits of Short-Acting Insulin analogues over regular human Insulin in people with type 2 diabetes. Overall, the certainty of the evidence was poor and results on patient-relevant outcomes, like all-cause mortality, microvascular or macrovascular complications and severe hypoglycaemic episodes were sparse. Long-term efficacy and safety data are needed to draw conclusions about the effects of Short-Acting Insulin analogues on patient-relevant outcomes.

  • Short Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • The Cochrane Library - Short‐Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • The Cochrane Library - Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

Johannes Plank - One of the best experts on this subject based on the ideXlab platform.

  • Short Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • The Cochrane Library - Short‐Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • The Cochrane Library - Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • systematic review and meta analysis of Short Acting Insulin analogues in patients with diabetes mellitus
    JAMA Internal Medicine, 2005
    Co-Authors: Johannes Plank, Andrea Siebenhofer, Andrea Berghold, Klaus Jeitler, Karl Horvath, Peter Mrak, Thomas R Pieber
    Abstract:

    Background This article compares the effect of treatment with Short-Acting Insulin (SAI) analogues vs regular Insulin on glycemic control, hypoglycemic episodes, quality of life, and diabetes-specific complications. Methods Electronic searches (Cochrane Library, MEDLINE, and EMBASE) and additional searching (pharmaceutical companies, experts, approval agencies, abstracts of diabetology meetings) were performed. Two reviewers independently screened randomized controlled trials to determine inclusion. Results Forty-two randomized controlled trials that assessed the effect of SAI analogues vs regular Insulin in 7933 patients with type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes mellitus were identified. The weighted mean difference between hemoglobin A 1c values obtained using SAI analogues and regular Insulin was −0.12% (95% confidence interval [CI], −0.17% to −0.07%) for adult patients with type 1 diabetes mellitus and −0.02% (95% CI, −0.10% to 0.07%) for patients with type 2 diabetes mellitus. The standardized mean difference for overall hypoglycemia (episodes per patient per month) was −0.05 (95% CI, −0.22 to 0.11) and −0.04 (95% CI, −0.12 to 0.04) comparing SAI analogues with regular Insulin in adult patients with type 1 and type 2 diabetes mellitus, respectively. No differences between treatments were observed in children with type 1 diabetes, pregnant women with type 1 diabetes mellitus, and women with gestational diabetes. Concerning quality of life, improvement was observed only in open-label studies in patients with type 1 diabetes mellitus. No differences were seen in a double-blinded study of patients with type 1 or in the studies of patients with type 2 diabetes mellitus. Conclusion Our analysis suggests only a minor benefit to hemoglobin A 1c values in adult patients with type 1 diabetes mellitus but no benefit in the remaining population with type 2 or gestational diabetes from SAI analogue treatment.

Andrea Berghold - One of the best experts on this subject based on the ideXlab platform.

  • Short-Acting Insulin analogues versus regular human Insulin for adult, non-pregnant persons with type 2 diabetes mellitus.
    Cochrane Database of Systematic Reviews, 2018
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    The use of Short-Acting Insulin analogues (Insulin lispro, Insulin aspart, Insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates. To assess the effects of Short-Acting Insulin analogues compared to regular human Insulin in adult, non-pregnant people with type 2 diabetes mellitus. For this update we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication. We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues to regular human Insulin in the treatment of people with type 2 diabetes, who were not pregnant. Two review authors independently extracted data and assessed the risk of bias. We assessed dichotomous outcomes by risk ratios (RR), and Peto odds ratios (POR), with 95% confidence intervals (CI). We assessed continuous outcomes by mean differences (MD) with 95% CI. We assessed trials for certainty of the evidence using the GRADE approach. We identified 10 trials that fulfilled the inclusion criteria, randomising 2751 participants; 1388 participants were randomised to receive Insulin analogues and 1363 participants to receive regular human Insulin. The duration of the intervention ranged from 24 to 104 weeks, with a mean of about 41 weeks. The trial populations showed diversity in disease duration, and inclusion and exclusion criteria. None of the trials were blinded, so the risk of performance bias and detection bias, especially for subjective outcomes, such as hypoglycaemia, was high in nine of 10 trials from which we extracted data. Several trials showed inconsistencies in the reporting of methods and results.None of the included trials defined all-cause mortality as a primary outcome. Six trials provided Information on the number of participants who died during the trial, with five deaths out of 1272 participants (0.4%) in the Insulin analogue groups and three deaths out of 1247 participants (0.2%) in the regular human Insulin groups (Peto OR 1.66, 95% CI 0.41 to 6.64; P = 0.48; moderate-certainty evidence). Six trials, with 2509 participants, assessed severe hypoglycaemia differently, therefore, we could not summarise the results with a meta-analysis. Overall, the incidence of severe hypoglycaemic events was low, and none of the trials showed a clear difference between the two intervention arms (low-certainty evidence).The MD in glycosylated haemoglobin A1c (HbA1c) change was -0.03% (95% CI -0.16 to 0.09; P = 0.60; 9 trials, 2608 participants; low-certainty evidence). The 95% prediction ranged between -0.31% and 0.25%. The MD in the overall number of non-severe hypoglycaemic episodes per participant per month was 0.08 events (95% CI 0.00 to 0.16; P = 0.05; 7 trials, 2667 participants; very low-certainty evidence). The 95% prediction interval ranged between -0.03 and 0.19 events per participant per month. The results provided for nocturnal hypoglycaemic episodes were of questionable validity. Overall, there was no clear difference between the two Short-Acting Insulin analogues and regular human Insulin. Two trials assessed health-related quality of life and treatment satisfaction, but we considered the results for both outcomes to be unreliable (very low-certainty evidence).No trial was designed to investigate possible long term effects (all-cause mortality, microvascular or macrovascular complications of diabetes), especially in participants with diabetes-related complications. No trial reported on socioeconomic effects. Our analysis found no clear benefits of Short-Acting Insulin analogues over regular human Insulin in people with type 2 diabetes. Overall, the certainty of the evidence was poor and results on patient-relevant outcomes, like all-cause mortality, microvascular or macrovascular complications and severe hypoglycaemic episodes were sparse. Long-term efficacy and safety data are needed to draw conclusions about the effects of Short-Acting Insulin analogues on patient-relevant outcomes.

  • Short Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • The Cochrane Library - Short‐Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • The Cochrane Library - Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

Karl Horvath - One of the best experts on this subject based on the ideXlab platform.

  • Short-Acting Insulin analogues versus regular human Insulin for adult, non-pregnant persons with type 2 diabetes mellitus.
    Cochrane Database of Systematic Reviews, 2018
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    The use of Short-Acting Insulin analogues (Insulin lispro, Insulin aspart, Insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates. To assess the effects of Short-Acting Insulin analogues compared to regular human Insulin in adult, non-pregnant people with type 2 diabetes mellitus. For this update we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication. We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues to regular human Insulin in the treatment of people with type 2 diabetes, who were not pregnant. Two review authors independently extracted data and assessed the risk of bias. We assessed dichotomous outcomes by risk ratios (RR), and Peto odds ratios (POR), with 95% confidence intervals (CI). We assessed continuous outcomes by mean differences (MD) with 95% CI. We assessed trials for certainty of the evidence using the GRADE approach. We identified 10 trials that fulfilled the inclusion criteria, randomising 2751 participants; 1388 participants were randomised to receive Insulin analogues and 1363 participants to receive regular human Insulin. The duration of the intervention ranged from 24 to 104 weeks, with a mean of about 41 weeks. The trial populations showed diversity in disease duration, and inclusion and exclusion criteria. None of the trials were blinded, so the risk of performance bias and detection bias, especially for subjective outcomes, such as hypoglycaemia, was high in nine of 10 trials from which we extracted data. Several trials showed inconsistencies in the reporting of methods and results.None of the included trials defined all-cause mortality as a primary outcome. Six trials provided Information on the number of participants who died during the trial, with five deaths out of 1272 participants (0.4%) in the Insulin analogue groups and three deaths out of 1247 participants (0.2%) in the regular human Insulin groups (Peto OR 1.66, 95% CI 0.41 to 6.64; P = 0.48; moderate-certainty evidence). Six trials, with 2509 participants, assessed severe hypoglycaemia differently, therefore, we could not summarise the results with a meta-analysis. Overall, the incidence of severe hypoglycaemic events was low, and none of the trials showed a clear difference between the two intervention arms (low-certainty evidence).The MD in glycosylated haemoglobin A1c (HbA1c) change was -0.03% (95% CI -0.16 to 0.09; P = 0.60; 9 trials, 2608 participants; low-certainty evidence). The 95% prediction ranged between -0.31% and 0.25%. The MD in the overall number of non-severe hypoglycaemic episodes per participant per month was 0.08 events (95% CI 0.00 to 0.16; P = 0.05; 7 trials, 2667 participants; very low-certainty evidence). The 95% prediction interval ranged between -0.03 and 0.19 events per participant per month. The results provided for nocturnal hypoglycaemic episodes were of questionable validity. Overall, there was no clear difference between the two Short-Acting Insulin analogues and regular human Insulin. Two trials assessed health-related quality of life and treatment satisfaction, but we considered the results for both outcomes to be unreliable (very low-certainty evidence).No trial was designed to investigate possible long term effects (all-cause mortality, microvascular or macrovascular complications of diabetes), especially in participants with diabetes-related complications. No trial reported on socioeconomic effects. Our analysis found no clear benefits of Short-Acting Insulin analogues over regular human Insulin in people with type 2 diabetes. Overall, the certainty of the evidence was poor and results on patient-relevant outcomes, like all-cause mortality, microvascular or macrovascular complications and severe hypoglycaemic episodes were sparse. Long-term efficacy and safety data are needed to draw conclusions about the effects of Short-Acting Insulin analogues on patient-relevant outcomes.

  • Short Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • The Cochrane Library - Short‐Acting Insulin analogues versus regular human Insulin for adults with type 1 diabetes mellitus
    Cochrane Database of Systematic Reviews, 2016
    Co-Authors: Birgit Fullerton, Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Thomas R Pieber, Thomas Semlitsch, Ferdinand M Gerlach
    Abstract:

    Background Short-Acting Insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. Objectives To assess the effects of Short-Acting Insulin analogues versus regular human Insulin in adults with type 1 diabetes. Search methods We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). Selection criteria We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared Short-Acting Insulin analogues with regular human Insulins in the treatment of adults with type 1 diabetes who were not pregnant. Data collection and analysis Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. Main results We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in the reporting of methods and results. The mean difference (MD) in glycosylated haemoglobin A1c (HbA1c) was -0.15% (95% CI -0.2% to -0.1%; P value < 0.00001; 2608 participants; 9 trials; low quality evidence) in favour of Insulin analogues. The comparison of the risk of severe hypoglycaemia between the two treatment groups showed an OR of 0.89 (95% CI 0.71 to 1.12; P value = 0.31; 2459 participants; 7 trials; very low quality evidence). For overall hypoglycaemia, also taking into account mild forms of hypoglycaemia, the data were generally of low quality, but also did not indicate substantial group differences. Regarding nocturnal severe hypoglycaemic episodes, two trials reported statistically significant effects in favour of the Insulin analogue, Insulin aspart. However, due to inconsistent reporting in publications and trial reports, the validity of the result remains questionable. We also found no clear evidence for a substantial effect of Insulin analogues on health-related quality of life. However, there were few results only based on subgroups of the trial populations. None of the trials reported substantial effects regarding weight gain or any other adverse events. No trial was designed to investigate possible long-term effects (such as all-cause mortality, diabetic complications), in particular in people with diabetes related complications. Authors' conclusions Our analysis suggests only a minor benefit of Short-Acting Insulin analogues on blood glucose control in people with type 1 diabetes. To make conclusions about the effect of Short Acting Insulin analogues on long-term patient-relevant outcomes, long-term efficacy and safety data are needed.

  • Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.

  • The Cochrane Library - Short Acting Insulin analogues versus regular human Insulin in patients with diabetes mellitus
    Cochrane Database of Systematic Reviews, 2006
    Co-Authors: Andrea Siebenhofer, Johannes Plank, Andrea Berghold, Klaus Jeitler, Karl Horvath, Markus Narath, Robert Gfrerer, Thomas R Pieber
    Abstract:

    Short Acting Insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of Short Acting Insulin analogues versus regular human Insulin.