Evidence mapPaperPMID 26916685Full record

Trial reportBMJ open2016

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 and 16 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in BMJ open, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT00657943. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00657943 phase4completed

The Effect of Metformin Versus Placebo, Including Three Insulin-Analogue Regimens With Variating Postprandial Glucose Regulation, on CIMT in T2DM Patients - A Randomized, Multicenter Trial

Ran2008Enrolled415Registered outcomes2Posted comparisons0ConditionsArteriosclerosis, Atherosclerosis, Type 2 DiabetesArmsInsulin Aspart, insulin aspart + insulin aspart protamin, insulin detemir, Metformin
Open the trial in the graph
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors at 9 institutions in 2 countries.

Louise Lundby-ChristensenSteno Diabetes Center, Gentofte, Denmark Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Paediatrics, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
Allan VaagSteno Diabetes Center, Gentofte, Denmark Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark University of Copenhagen, Copenhagen, Denmark.
Lise TarnowSteno Diabetes Center, Gentofte, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark Department of Health, University of Aarhus, Aarhus, Denmark.
Thomas P AlmdalDepartment of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Søren S LundSteno Diabetes Center, Gentofte, Denmark Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
Jørn WetterslevCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Christian GluudCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Trine W BoesgaardSteno Diabetes Center, Gentofte, Denmark.
Niels WiinbergDepartment of Physiology and Nuclear Medicine, Frederiksberg, Copenhagen University Hospital, Frederiksberg, Denmark.
Hans PerrildDepartment of Endocrinology, Bispebjerg, Copenhagen University Hospital, Copenhagen, Denmark.
Thure KrarupDepartment of Endocrinology, Bispebjerg, Copenhagen University Hospital, Copenhagen, Denmark.
Ole SnorgaardDepartment of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
Birthe Gade-RasmussenDepartment of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
Birger ThorsteinssonUniversity of Copenhagen, Copenhagen, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark.
Michael RøderDepartment of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark Department of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
Elisabeth R MathiesenDepartment of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark University of Copenhagen, Copenhagen, Denmark.
Tonny JensenDepartment of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Henrik VestergaardUniversity of Copenhagen, Copenhagen, Denmark Department of Endocrinology, Herlev, Copenhagen University Hospital, Herlev, Denmark Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Christoffer HedetoftDepartment of Medicine, University Hospital Køge, Køge, Denmark.
Leif BreumDepartment of Medicine, University Hospital Køge, Køge, Denmark.
Elsebeth DuunDepartment of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
Simone B SneppenDepartment of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
Oluf PedersenSteno Diabetes Center, Gentofte, Denmark University of Copenhagen, Copenhagen, Denmark Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Bianca HemmingsenCopenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark.
Bendix CarstensenSteno Diabetes Center, Gentofte, Denmark.
Sten MadsbadDepartment of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark University of Copenhagen, Copenhagen, Denmark.
Copenhagen University Hospital · DKSteno Diabetes Center · DKGentofte Hospital · DKRigshospitalet · DKUniversity of Copenhagen · DKNordsjællands Hospital · DKZealand University Hospital Køge · DKBoehringer Ingelheim (Germany) · DEHvidovre Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes. DESIGN AND

settingInvestigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design, conducted at 8 hospitals in Denmark. PARTICIPANTS AND

interventionsParticipants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 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 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.

resultsCarotid 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.

conclusionsCarotid 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. TRIAL REGISTRATION NUMBER: NCT00657943.

Indexed as

Carotid Intima-Media ThicknessBlood GlucoseBody WeightDenmarkDiabetes Mellitus, Type 2Drug Administration ScheduleFemaleGlycated HemoglobinHumansHypoglycemiaHypoglycemic AgentsInsulinInsulin AspartInsulin DetemirMaleMetforminBlood GlucoseGlycated HemoglobinHypoglycemic AgentsInsulinInsulin AspartInsulin DetemirMetforminULTRASONOGRAPHY

Identifiers

PMID26916685
PMCPMC4771974
OpenAlexW2297859973

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.