Cargando…
Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial
OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTIC...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771974/ https://www.ncbi.nlm.nih.gov/pubmed/26916685 http://dx.doi.org/10.1136/bmjopen-2015-008377 |
_version_ | 1782418479750578176 |
---|---|
author | Lundby-Christensen, Louise Vaag, Allan Tarnow, Lise Almdal, Thomas P Lund, Søren S Wetterslev, Jørn Gluud, Christian Boesgaard, Trine W Wiinberg, Niels Perrild, Hans Krarup, Thure Snorgaard, Ole Gade-Rasmussen, Birthe Thorsteinsson, Birger Røder, Michael Mathiesen, Elisabeth R Jensen, Tonny Vestergaard, Henrik Hedetoft, Christoffer Breum, Leif Duun, Elsebeth Sneppen, Simone B Pedersen, Oluf Hemmingsen, Bianca Carstensen, Bendix Madsbad, Sten |
author_facet | Lundby-Christensen, Louise Vaag, Allan Tarnow, Lise Almdal, Thomas P Lund, Søren S Wetterslev, Jørn Gluud, Christian Boesgaard, Trine W Wiinberg, Niels Perrild, Hans Krarup, Thure Snorgaard, Ole Gade-Rasmussen, Birthe Thorsteinsson, Birger Røder, Michael Mathiesen, Elisabeth R Jensen, Tonny Vestergaard, Henrik Hedetoft, Christoffer Breum, Leif Duun, Elsebeth Sneppen, Simone B Pedersen, Oluf Hemmingsen, Bianca Carstensen, Bendix Madsbad, Sten |
author_sort | Lundby-Christensen, Louise |
collection | PubMed |
description | OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA(1c))≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA(1c)≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA(1c), insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. RESULTS: Carotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA(1c) was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ. CONCLUSIONS: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA(1c), weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943. |
format | Online Article Text |
id | pubmed-4771974 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-47719742016-03-01 Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial Lundby-Christensen, Louise Vaag, Allan Tarnow, Lise Almdal, Thomas P Lund, Søren S Wetterslev, Jørn Gluud, Christian Boesgaard, Trine W Wiinberg, Niels Perrild, Hans Krarup, Thure Snorgaard, Ole Gade-Rasmussen, Birthe Thorsteinsson, Birger Røder, Michael Mathiesen, Elisabeth R Jensen, Tonny Vestergaard, Henrik Hedetoft, Christoffer Breum, Leif Duun, Elsebeth Sneppen, Simone B Pedersen, Oluf Hemmingsen, Bianca Carstensen, Bendix Madsbad, Sten BMJ Open Diabetes and Endocrinology OBJECTIVE: To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND SETTING: Investigator-initiated, randomised, placebo-controlled trial with a 2×3 factorial design, conducted at 8 hospitals in Denmark. PARTICIPANTS AND INTERVENTIONS: Participants with type 2 diabetes (glycated haemoglobin (HbA(1c))≥7.5% (≥58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1–3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA(1c)≤7.0% (≤53 mmol/mol). OUTCOMES: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA(1c), insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes. RESULTS: Carotid IMT change did not differ between groups (biphasic −0.009 mm (95% CI −0.022 to 0.004), aspart+detemir 0.000 mm (95% CI −0.013 to 0.013), detemir −0.012 mm (95% CI −0.025 to 0.000)). HbA(1c) was more reduced with biphasic (−1.0% (95% CI −1.2 to −0.8)) compared with the aspart+detemir (−0.4% (95% CI −0.6 to −0.3)) and detemir (−0.3% (95% CI −0.4 to −0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ. CONCLUSIONS: Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA(1c), weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results. TRIAL REGISTRATION NUMBER: NCT00657943. BMJ Publishing Group 2016-02-25 /pmc/articles/PMC4771974/ /pubmed/26916685 http://dx.doi.org/10.1136/bmjopen-2015-008377 Text en Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/ This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Diabetes and Endocrinology Lundby-Christensen, Louise Vaag, Allan Tarnow, Lise Almdal, Thomas P Lund, Søren S Wetterslev, Jørn Gluud, Christian Boesgaard, Trine W Wiinberg, Niels Perrild, Hans Krarup, Thure Snorgaard, Ole Gade-Rasmussen, Birthe Thorsteinsson, Birger Røder, Michael Mathiesen, Elisabeth R Jensen, Tonny Vestergaard, Henrik Hedetoft, Christoffer Breum, Leif Duun, Elsebeth Sneppen, Simone B Pedersen, Oluf Hemmingsen, Bianca Carstensen, Bendix Madsbad, Sten Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title | Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title_full | Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title_fullStr | Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title_full_unstemmed | Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title_short | Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial |
title_sort | effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised copenhagen insulin and metformin therapy (cimt) trial |
topic | Diabetes and Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771974/ https://www.ncbi.nlm.nih.gov/pubmed/26916685 http://dx.doi.org/10.1136/bmjopen-2015-008377 |
work_keys_str_mv | AT lundbychristensenlouise effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT vaagallan effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT tarnowlise effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT almdalthomasp effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT lundsørens effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT wetterslevjørn effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT gluudchristian effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT boesgaardtrinew effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT wiinbergniels effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT perrildhans effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT krarupthure effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT snorgaardole effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT gaderasmussenbirthe effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT thorsteinssonbirger effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT rødermichael effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT mathiesenelisabethr effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT jensentonny effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT vestergaardhenrik effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT hedetoftchristoffer effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT breumleif effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT duunelsebeth effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT sneppensimoneb effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT pedersenoluf effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT hemmingsenbianca effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT carstensenbendix effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial AT madsbadsten effectsofbiphasicbasalbolusorbasalinsulinanaloguetreatmentsoncarotidintimamediathicknessinpatientswithtype2diabetesmellitustherandomisedcopenhageninsulinandmetformintherapycimttrial |