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

Louise Lundby-Christensen; Allan Vaag; Lise Tarnow; Thomas P Almdal; Søren S Lund; Jørn Wetterslev; Christian Gluud; Trine W Boesgaard; Niels Wiinberg; Hans Perrild; Thure Krarup; Ole Snorgaard; Birthe Gade-Rasmussen; Birger Thorsteinsson; Michael Røder; Elisabeth R Mathiesen; Tonny Jensen; Henrik Vestergaard; Christoffer Hedetoft; Leif Breum; Elsebeth Duun; Simone B Sneppen; Oluf Pedersen; Bianca Hemmingsen; Bendix Carstensen; Sten Madsbad

doi:10.1136/bmjopen-2015-008377

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

Louise Lundby-Christensen, Allan Vaag, Lise Tarnow, Thomas P Almdal, Søren S Lund, Jørn Wetterslev, Christian Gluud, Trine W Boesgaard, Niels Wiinberg, Hans Perrild, Thure Krarup, Ole Snorgaard, Birthe Gade-Rasmussen, Birger Thorsteinsson, Michael Røder, Elisabeth R Mathiesen, Tonny Jensen, Henrik Vestergaard, Christoffer Hedetoft, Leif BreumElsebeth Duun, Simone B Sneppen, Oluf Pedersen, Bianca Hemmingsen, Bendix Carstensen, Sten Madsbad

9 Citations (Scopus)

Abstract

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/m2) 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.

Original language	English
Article number	e008377
Journal	B M J Open
Volume	6
Issue number	2
ISSN	2044-6055
DOIs	https://doi.org/10.1136/bmjopen-2015-008377
Publication status	Published - 2016

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Lundby-Christensen, L., Vaag, A., Tarnow, L., Almdal, T. P., Lund, S. S., Wetterslev, J., Gluud, C., Boesgaard, T. W., Wiinberg, N., Perrild, H., Krarup, T., Snorgaard, O., Gade-Rasmussen, B., Thorsteinsson, B., Røder, M., Mathiesen, E. R., Jensen, T., Vestergaard, H., Hedetoft, C., ... Madsbad, S. (2016). 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. B M J Open, 6(2), Article e008377. https://doi.org/10.1136/bmjopen-2015-008377

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 et al.
In: B M J Open, Vol. 6, No. 2, e008377, 2016.

Research output: Contribution to journal › Journal article › Research › peer-review

Lundby-Christensen, L, Vaag, A, Tarnow, L, Almdal, TP, Lund, SS, Wetterslev, J, Gluud, C, Boesgaard, TW, Wiinberg, N, Perrild, H, Krarup, T, Snorgaard, O, Gade-Rasmussen, B, Thorsteinsson, B, Røder, M, Mathiesen, ER, Jensen, T, Vestergaard, H, Hedetoft, C, Breum, L, Duun, E, Sneppen, SB, Pedersen, O, Hemmingsen, B, Carstensen, B & Madsbad, S 2016, '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', B M J Open, vol. 6, no. 2, e008377. https://doi.org/10.1136/bmjopen-2015-008377

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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",

abstract = "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 (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m2) 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 HbA1c≤7.0% (≤53 mmol/mol). Outcomes: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, 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)). HbA1c 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 HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.",

author = "Louise Lundby-Christensen and Allan Vaag and Lise Tarnow and Almdal, {Thomas P} and Lund, {S{\o}ren S} and J{\o}rn Wetterslev and Christian Gluud and Boesgaard, {Trine W} and Niels Wiinberg and Hans Perrild and Thure Krarup and Ole Snorgaard and Birthe Gade-Rasmussen and Birger Thorsteinsson and Michael R{\o}der and Mathiesen, {Elisabeth R} and Tonny Jensen and Henrik Vestergaard and Christoffer Hedetoft and Leif Breum and Elsebeth Duun and Sneppen, {Simone B} and Oluf Pedersen and Bianca Hemmingsen and Bendix Carstensen and Sten Madsbad",

note = "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/",

year = "2016",

doi = "10.1136/bmjopen-2015-008377",

language = "English",

volume = "6",

journal = "B M J Open",

issn = "2044-6055",

publisher = "BMJ Publishing Group",

number = "2",

}

TY - JOUR

T1 - Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus

T2 - the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial

AU - Lundby-Christensen, Louise

AU - Vaag, Allan

AU - Tarnow, Lise

AU - Almdal, Thomas P

AU - Lund, Søren S

AU - Wetterslev, Jørn

AU - Gluud, Christian

AU - Boesgaard, Trine W

AU - Wiinberg, Niels

AU - Perrild, Hans

AU - Krarup, Thure

AU - Snorgaard, Ole

AU - Gade-Rasmussen, Birthe

AU - Thorsteinsson, Birger

AU - Røder, Michael

AU - Mathiesen, Elisabeth R

AU - Jensen, Tonny

AU - Vestergaard, Henrik

AU - Hedetoft, Christoffer

AU - Breum, Leif

AU - Duun, Elsebeth

AU - Sneppen, Simone B

AU - Pedersen, Oluf

AU - Hemmingsen, Bianca

AU - Carstensen, Bendix

AU - Madsbad, Sten

N1 - 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/

PY - 2016

Y1 - 2016

N2 - 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 (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m2) 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 HbA1c≤7.0% (≤53 mmol/mol). Outcomes: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, 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)). HbA1c 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 HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.

AB - 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 (HbA1c)≥7.5% (≥58 mmol/mol), body mass index >25 kg/m2) 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 HbA1c≤7.0% (≤53 mmol/mol). Outcomes: Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, 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)). HbA1c 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 HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.

U2 - 10.1136/bmjopen-2015-008377

DO - 10.1136/bmjopen-2015-008377

M3 - Journal article

C2 - 26916685

SN - 2044-6055

VL - 6

JO - B M J Open

JF - B M J Open

IS - 2

M1 - e008377

ER -