Are concomitant treatments confounding factors in randomized controlled trials on intensive blood-glucose control in type 2 diabetes? a systematic review.
BACKGROUND
Open-label, randomized controlled trials (RCTs) are subject to observer bias. If patient management is conducted without blinding, a difference between groups may be explained by other factors than study treatment. One factor may come from taking concomitant treatments with an efficacy on the studied outcomes. In type 2 diabetes, some antihypertensive or lipid-lowering drugs are effective against diabetic complications. We wanted to determine if these concomitant treatments were correctly reported in articles of RCTs on type 2 diabetes and if they might have influenced the outcome.


METHODS
We performed a systematic review using Medline, Embase, and the Cochrane Library (from January 1950 to July 2010). Open-label RCTs assessing the effectiveness of intensive blood-glucose control in type 2 diabetes were included. We chose five therapeutic classes with proven efficacy against diabetes complications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor antagonists (AIIRAs), fibrates, statins, and aspirin. Differences between concomitant treatments were considered statistically significant when p < 0.05.


RESULTS
A total of eight open-label RCTs were included, but only three (37.5%) of them published concomitant treatments. In two studies (ACCORD and ADVANCE), a statistically significant difference was observed between the two groups for aspirin (p = 0.02) and ACEIs (p = 0.02).


CONCLUSIONS
Few concomitant treatments were published in this sample of open-label RCTs. We cannot completely eliminate an observer bias for these studies. This bias probably influenced the results to an extent that has yet to be determined.
UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, CNRS, Université Claude Bernard Lyon 1, Villeurbanne F-69100, France. francois.gueyffier@chu-lyon.fr.
Rémy
R
Boussageon
Irène
I
Supper
Sylvie
S
Erpeldinger
Michel
M
Cucherat
Theodora
T
Bejan-Angoulvant
Behrouz
B
Kassai
Catherine
C
Cornu
François
F
Gueyffier
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose; D015986:Confounding Factors, Epidemiologic; D048909:Diabetes Complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015588:Observer Variation; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents