Co-interests

1. Co-interests • Editor: ACP Journal Club, Evidence-Based Medicine • Supplier: bmjupdates+, PIER, Clinical Evidence, Medscape

2. CANADIAN SOCIETY OF INTERNAL MEDICINE ANNUAL SCIENTIFIC MEETING NOVEMBER 1-4, 2006 1500-1730 SHORT SNAPPERS 1. Perioperative AMI - Dr. Akbar Panju, Hamilton 2. Optimal Asthma Management - Dr. Tony Bai, Vancouver 3. Incretins – TBA 4. New Insulins – TBA 5. New Method for Rapid HIV Testing - Dr. Donna Sweet, Wichita Incretin Therapy in Type 2 Diabetes Type 2 Diabetes in Canada. Where are we going. Irene Hramiak, UWO (sponsored by Merck) 11:45 – 13:00 Peter Bolli approached me to make a presentation at the ACP meeting in Toronto

3. Advances in Resources for Evidence-Based Clinical Practice How to Determine for Yourself What Recent Studies You Should be Paying Attention To Brian Haynes Health Information Research Unit McMaster University

4. 58 y/o obese male with …type 2 DM …A1c 9% on glyburide and rosiglitazone, with metformin intolerance…continuing to gain weight…veryreluctant to take insulin Can incretin therapy help? (exenatide, pramlintide, sitagliptin)

5. EBHC is... …a set of procedures, pre-appraised resources and information tools to assist practitioners to apply evidence from research in the care of individual patients.

6. Examples Computerized decision support Evidence-based textbooks Evidence-based journal abstracts Systematic reviews Original journal articles New School EBM Olde School EBM

7. Evidence-basedPush, Pull, Prompt …ways to deal with too much information

8. Push:

9. Evidence-Based Journals Critical Appraisal Filters ~3000 articles/yr meet critical appraisal and content criteria (95% noise reduction) 60,000 articles/yr from 120 journals

10. McMaster PLUS Project Clinical Relevancy Filter (MORE) ~25 articles/yr for clinicians (99.995% noise reduction) ~3,000 articles/yr meet critical appraisal and content criteria (95% noise reduction) ~5-50 articles/yr for authors of evidence-based clinical topic reviews

11. User End • Users sign up according to discipline • Users control relevance and flow • Users can change disciplines at any time, and can sign up for as many as they wish • Users can search according to discipline – or not • Users can access PubMed Clinical Queries

12. Self Serve Version Ovid Stat!Ref Pyramid of Evidence Full Serve Version Ovid Stat! Ref Pyramid of Evidence PLUS Email Alerts PLUS Search Engine Randomized Trial of PLUS Randomization to 2 different trial interfaces: PULL + PUSH PULL

13. RCT begins Control cross-over begins PLUS Findings: % of Participants Using PLUS by Month Self-servevsFull-serve Baseline (5 mo) Full-Serve 70 60 50 40 30 20 10 0 Percentage Using PLUS Relative increase 58.7%, P=0.001 Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun 03 03 04 04 04 04 04 04 04 04 04 04 04 04 05 05 05 05 05 05 Month Haynes et al, JAMIA Nov 2006 Self-serve Full-Serve

14. Free at http://bmjupdates.mcmaster.ca

15. CONCLUSIONS: Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine. (19% withdrew on exenatide, 9.7% on glargine)

16. The major adverse effects associated with pramlintide include an increase in nausea or anorexia, and possible hypoglycemia…several concerns with the published literature still exist. Must be injected. Costs $100-200/mo.

17. CONCLUSIONS: In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states {vs placebo}, improved measures of beta-cell function, and was well tolerated in patients with type 2 diabetes.

18. (My) “push” conclusions • Interesting but not enough to warrant a change in practice • Short-term trials with wrong comparators • Adverse effects • Expensive • Sitagliptin (Januvia) - $6/pill • Exenatide (Byetta) - $10/dose • Pramlintide ?? Metformin $0.25/pill Glyburide $0.20/pill Pioglitazone $1.00/pill

19. PULL: Resources for Finding Evidence When You Need it

20. Examples Computerized decision support Evidence-based textbooks Evidence-based journal abstracts Systematic reviews Original journal articles

21. Premier evidence resources for internal medicine • Systems: EMR with decision support • Summaries: Clinical Evidence, PIER, UpToDate, Dynamed • Synopses: ACP Journal Club • Syntheses: via BMJUpdates+ • Studies: via BMJUpdates, PubMed Clinical Queries

22. 58 y/o obese male with …type 2 DM …A1c 9% on glyburide and rosiglitazone, with metformin intolerance…continuing to gain weight…very reluctant to take insulin Can exenatide, pramlintide or sitagliptin help?

23. For type 2 diabetes, what are the effects- good and bad -of incretin therapy? • Systems: none • Summaries: in UTD, PIER, Dynamed, not CE • Synopses: sitagliptin in ACP JC • Syntheses: one for pramlintide in BMJUpdates+ • Studies: exenatide and pramlintide in UTD, PIER, CE, BMJUpdates+; more on exenatide, pramlintide and sitagliptin in Clinical Queries

24. Januvia is approved for use by people with type 2 diabetes that can't be controlled adequately with diet and exercise. Section updated June 2006; update scheduled February 2007 (not available; no GRADE yet) “Many questions remain unanswered regarding clinical use and long-term outcomes with these drugs.” Sitagliptin is stated to be “experimental” {but is now FDA approved (October 17, 2006)} $6 per pill

25. Includes exenatide, pramlintide, and sitagliptin, with drug monographs for each • “Consider metformin as a first-line agent because it causes less hypoglycemia and weight gain, along with possible improvements in cardiovascular risk.” • “Consider other oral agents, such as sulfonylureas, thiazolidinediones, and DPP-IV inhibitors, as reasonable first-line agents, although some are costly and the long-term benefits of these drugs have not been well studied.”

26. CONCLUSIONS: Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine. (19% withdrew on exenatide, 9.7% on glargine)

27. CONCLUSIONS: In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states {vs placebo}, improved measures of beta-cell function, and was well tolerated in patients with type 2 diabetes.

28. The major adverse effects associated with pramlintide include an increase in nausea or anorexia, and possible hypoglycemia…several concerns with the published literature still exist. Must be injected. Costs $100-200/mo.

29. Survey of traditional texts • Harrison’s – no; Harrison’s Practice - yes • Books@Ovid – no • Stat!Ref – in PIER and Mosby Drug Consult • Kelley’s Textbook - no

30. My conclusions about exenatide, pramlintide, gliptins • Interesting new options for diabetes • Not well studied (eg, no head-to-head studies with current agents) • Exenatide and pramlintide would likely be out for this patient (injections) • Sitagliptin would be a possibility, but not until better known options tried (acarbose, Avandamet, repaglinide)

32. To keep up • Pull • Push • Prompt…some labs and EMRs with a credible evidence-based pedigree (Zynx)

33. Any questions?