Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database

Abstract

Objective To investigate the risk of incident myocardial infarction, congestive heart failure, and all cause mortality associated with prescription of oral antidiabetes drugs. Design Retrospective cohort study. Setting UK general practice research database, 1990-2005. Participants 91 521 people with diabetes. Main outcome measures Incident myocardial infarction, congestive heart failure, and all cause mortality. Person time intervals for drug treatment were categorised by drug class, excluding non-drug intervals and intervals for insulin.Results 3588 incident cases of myocardial infarction, 6900 of congestive heart failure, and 18 548 deaths occurred. Compared with metformin, monotherapy with first or second generation sulphonylureas was associated with a significant 24% to 61% excess risk for all cause mortality (P<0.001) and second generation sulphonylureas with an 18% to 30% excess risk for congestive heart failure (P=0.01 and P<0.001). The thiazolidinediones were not associated with risk of myocardial infarction; pioglitazone was associated with a significant 31% to 39% lower risk of all cause mortality (P=0.02 to P<0.001) compared with metformin. Among the thiazolidinediones, rosiglitazone was associated with a 34% to 41% higher risk of all cause mortality (P=0.14 to P=0.01) compared with pioglitazone. A large number of potential confounders were accounted for in the study; however, the possibility of residual confounding or confounding by indication (differences in prognostic factors between drug groups) cannot be excluded. Conclusions Our findings suggest a relatively unfavourable risk profile of sulphonylureas compared with metformin for all outcomes examined. Pioglitazone was associated with reduced all cause mortality compared with metformin. Pioglitazone also had a favourable risk profile compared with rosiglitazone;

Insulinosensibilisateurs (metformine/glitazones) : niveau de preuve et controverse

“…Après ajustement pour divers facteurs potentiellement confondants, la metformine s'est révélée être associée à moins d'événements CV que les sulfamides hypoglycémiants [17][18][19][20]. De même, la metformine s'est montrée plus favorable que l'acarbose, l'inhibiteur des α-glucosidases de référence [21], et également légèrement meilleure, quoi que de façon non significative, que la sitagliptine, le leader de la classe des inhibiteurs de la dipeptidylpeptidase-IV (DPP-4) [22].…”

“…Dans ces études, la pioglitazone s'est révélée être associée à un meilleur pronostic CV (hormis le risque d'insuffisance cardiaque qui était accru) que la metformine [18] ou qu'un sulfamide hypoglycémiant chez des patients par ailleurs déjà traités par metformine [31]. De plus, quelques études observationnelles ont comparé le devenir de patients DT2 traités par glitazones, et ont montré que la pioglitazone était associée à un meilleur pronostic que la rosiglitazone [18,32].…”

Survival in people with type 2 diabetes as a function of HbA1c

“…No information is provided about the actual insulin or oral doses, or drugs used for treatment. A study 10 that used the same database showed that first-generation sulphonylurea monotherapy was associated with higher mortality (HR 1·37, 1·11-1·71) than was second-generation sulphonylurea monotherapy (HR 1·24, 1·14-1·35) compared with metformin. Another study from the Saskatchewan Health administrative databases 11 implicated insulin exposure with increased mortality, with a dose-response relation in patients with type 2 diabetes.…”

Should the algorithm for the treatment of type 2 diabetes be evidence-based?

“…In the UKPDS and ADOPT, the effect of sulfonylureas on cardiovascular endpoints was favourable too, even in comparison with metformin, as in ADOPT [5]. More surprisingly, Schernthaner et al report the results of observational studies analysing cardiovascular events, such as that of Tzoulaki et al [10], published in the BMJ in 2009. This study represents the paradigm of a nonevidence-based study due to a retrospective design and multiplicity of flaws.…”