FINDING THE EVIDENCE

1. FINDING THE EVIDENCE Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus Alvaro Alés Ruiz. R-2 MFyC. Area II of the Malaga Community and Family Medicine Teaching Unit

2. Are the results valid? Didthereviewexplicitlyaddress a sensible clinicalquestion? Notcompletely. Thearticleexplainssomeaspectsaboutthetreatment in the Diabetes Mellitusfollow-up, apartfromthe control of theglycemia. Thisfact has happenedbecausethearticleisbasedonmanystudies, whichconsiderdifferentaspects. Itisalsoinfluencedbyothereventsonthefollow-up.

3. Some of the aspects which influence the article because they are also included in the studies are: • Lowering-lipid treatment . • Blood pressure control. • Body mass index. • Previous disease. • Kind of population (eastern people, men between 53-66 years) • HbA1 concentration. • Time from diagnosis of Diabetes.

4. The article also gives information about other events during the follow-up: • Non-fatal myocardial infarction • Coronary heart disease • Stroke • All-cause mortality And other events linked with the glucose-lowering treatment: • Hypoglycaemia • Weight gain.

5. In conclusion: The article gives a valuable information about the pros and cons of the intensive glucose-lowering treatment , but does not adress, sufficiently in my opinion, the clinical question

6. Wasthesearchforrelevantstudiesdetalided and exhaustive? Yes. ItusedMedline, Cochrane, and EmBasefrom 1970 to 2009. ItrestrictedthesearchtoRandomisedcontrolledtrials, wichprovided 2439 articles, and furtherscreenedforinclusion: • Titles. • Abstracts. • Full texts. And supplementedtheelectronicsearchfromreferencelists of relevantarticleswith: • Meta-analyses. • Reviews. • And bydiscussionwithexperts.

7. Were the primary studies of high methodological quality? In an review, sometimes it is difficult to seek the quality of the selected studies. It uses explicit methodological criteria according to the main aspects about the article is. Therefore, I think it uses the necessary studies; which are: • The UKPDS 33: control with sulphonylureas or insulin compared with usual care. • The UKPds 34: control with metformin compared with diet. • The Proactrive: prospective pioglitazone clinical trial en macrovascular disease. • The ADVANCE: Action in Vascular Disease, Preterax and diamicron. • The VADT: Veterans Affairs Diabetes Trial. • The ACCORD: Action to Control Cardiovascular Risk in Diabetes trial • The Overall studies.

8. The reason to have this opinion is that the studies are made with a huge number of patients and the follow-up was for a long time and it takes into account many different aspects which were commented in the first question and also it considers the main methodological features of the RCT.

9. Were assessments of studies reproducible? Yes, it gathered information in duplicate using a standardised format from all relevant studies and it used another investigator to avoid possible errors. The investigator is called KKR

10. What are the results? Were the results similar from study to study? Despite the inclusion criteria, the studies are different among them. They have similar parameters, but there are differences between individuals and groups of patients; some aspects are similar (as we can see from the heterogeneity tests and from the graph part of the results) as the reduction on non-fatal myocardial infarction on the intensive glucose control pool, but in other causes of mortality, it did not significantly affect them (stroke, all-cause mortality). In consequence of this; this matter should be analysed in a deeper way.

11. What are the overall results of the review? The findings provide reassurance about the effectiveness of glycaemic control for: - Cardiovascular risk reduction, but have not proved a clear benefit to all-cause mortality.

12. How precise were the results? The confidence intervals of the overall calculation are narrow so I think the results were precise.

13. How can I apply the results to patient care? How can I best interpret the results to apply them to the care of patients in my practice? There is not a strong evidence about the benefits of exhaustive control of glycaemia, and we have to consider the risk of hypoglycaemia. There are also others aspects which have been proved as important factors to reduce mortality in the patients; which have been lipid-lowering treatment and blood pressure reduction, among others, so it is interesting to apply these matters to the diary clinical practice

14. Were all clinically important outcomes considered? Not completely, because most of the patients from all the studies were men between 53-66 years old, from n eastern population , with the diagnosis at least 8 years ago, and there were many aspects which were not explained in every pool of patients (as previous disease, concomitant events, among others)

15. Are the benefits worth the costs and potential risks? If we consider only the glycaemic control, there is no clear benefit, but there are others which worth the costs. (lipid treatment and blood pressure control). Therefore, the article gives us a beginning to take into account more important aspects apart from the glucose level, which are proven to reduce mortality in our patients, which we shall study.