Gliclazide MR in the management of Type 2 Diabetes Mellitus

Symposium on 10th June, 2013. Presented by Dr. Nazma Akhter (Phase B Resident, Endocrinology)

1. GLICLAZIDE MR IN THE MANAGEMENT OF TYPE 2 DM Dr. Nazma Akhtar Resident phase B Department of Endocrinology BSMMU

2. 3/28/2013 3

3. 3/28/2013 4

4. SULFONYLUREA: OAD agent Mode of action: Sulfonylureas act directly on the β - cells of the islets of Langerhans to stimulate insulin secretion They enter the β – cell and bind to the cytosolic surface of the sulfonylurea receptor 1 Binding of a sulfonylurea closes the K + ATP channel , reducing the efflux of potassium enabling membrane depolarization Localized membrane depolarization opens adjacent voltage - dependent L - type calcium channels Increasing calcium influx and raising the cytosolic free calcium concentration Mediate the exocytotic release of insulin granules

5. Classification Divided into first and second generation agents In general, the second-generation agents Are more potent Have fewer adverse effects and drug-drug interactions

6. Extended release preparations Extended-release glipizide and glimepiride are preferred agents because - they can be given once daily - involve a relatively low risk of hypoglycemia -low weight gain

7. Modified release preparations A “ modified release ” (MR) formulation of gliclazide has been introduced for once - daily dosing Interestingly , the 30 mg preparation of gliclazide MR gives similar efficacy to 80 mg of unmodified gliclazide and reduces risk of severe hypoglycemia

8. Target HbA1c <7% instead of <6.5% Evidence based alternative approach SU as 1 st line, irrespective of BMI TZD & DPP-4 inhibitor are 3 rd option What’s NEW in the treatment algorithm of IDF Guideline 2012?

9. Which SU to choose- gliclazide 80, glimepiride or the new Diamicron MR 60 ? ?

10. One of the largest clinical studies ever performed in type 2 diabetes N Engl J Med. 2008;358:2560-2572

11. More than 11,000 type 2 diabetic patients from 20 countries worldwide 4 Asian countries- China, India, Malaysia & Philippines N Engl J Med. 2008;358:2560-2572

12. Aim of the study What benefits can be gained from intensive glycemic control (HbA1c ≤6.5%) versus standard control? N Engl J Med. 2008;358:2560-2572

13. Strategy & Timeline Mean duration 5 years Strategy: treatment initiation with 60 mg Diamicron MR, increase up to 120 mg then add other therapy June 2001 January 2002 January 2003 January 2004 January 2005 January 2006 January 2007 January 2008 Blood glucose lowering comparison Recruitment period N Engl J Med. 2008;358:2560-2572

14. Results & Outcomes N Engl J Med. 2008;358:2560-2572. Diabetes Care 32:2068–2074, 2009. Diabetes Res Clin Pract . 2010;89:126-133.

15. Reduces HbA1c ≤7% within 6 months N Engl J Med. 2008;358:2560-2572

16. Reduces HbA1c by more than 4% unlike other SU N Engl J Med. 2008;358:2560-2572

17. Reduces HbA1c ≤7% irrespective of BMI N Engl J Med. 2008;358:2560-2572

18. Lowest episodes of hypoglycemia compared to other large scale clinical trials 1. N Engl J Med . 2008;358:2560-2572. 2. N Engl J Med . 2008;358:2545-2559. 3. Lancet . 1998;352:837-853.

19. Lowest hypoglycemia compared to DPP4-inhibitor Int J Clin Pract. 2011;65:1132-1140. Curr Med Res Opin 2012; 28:1–8 Middle East   India & Malaysia MORE EVIDENCES

20. Weight neutral unlike other SU N Engl J Med. 2008;358:2560-2572 5 YEARS DATA

21. Significantly reduces combined micro & macro vascular complications N Engl J Med. 2008;358:2560-2572

22. Opposite outcome compared to other trials using glimepiride N Engl J Med. 2008;358:2545-2559. N Engl J Med. 2008;358:2560-2572. N Engl J Med. 2009;360. MORE EVIDENCES

23. Better CV protection than Metformin & glimepiride Eur Heart J. 2011 Aug;32(15):1900-8. MORE EVIDENCES

24. Reduces End-stage Kidney Disease unlike any other OAD Diabetologia . 2011;54(suppl 1):S23. RECENT ANALYSIS

25. Reduces Beta cell apoptosis unlike glimepiride Metabolism. 2008;57:1038-1045. MORE EVIDENCES

26. Prolongs insulin free period Diabetes Res Clin Pract. 2005;70:291-297. While maintains HbA1c <7% for 14.5 years!!

27. FACT: EFficacy & tolerAbility of DiamiCron MR60 at the dosage of 1.5 to 2 tablets at breakfast over Bangladeshi Type 2 diabetic patients

28. A clinical study conducted by Bangladeshi clinicians over Bangladeshi type 2 diabetic patients

29. Objective of the study To observe efficacy and tolerability of Diamicron MR60 at the dosage of 1.5 to 2 tablets over Bangladeshi type 2 diabetic patients

30. Findings

31. Patient characteristics Characteristics (N= 359) Male (166) 166 (n) Female (193) 193 (n) Mean Age (279) 51 yrs ± 11 Mean Height (75) 1.5 m ± 0.6 Mean Weight (219) 64 kgs ± 9 Mean BMI (96) 26 ± 3

32. Efficacy: Reduction of HbA1c (Total Patients) -1.9% HbA1c reduction within 6 months -1.9% n= 359 8.9% 7.0%

33. Tolerability Only 1.0% hypoglycemia was found!! Baseline After 6 months Change Weight ( kgs ) 63.7 63.3 -0.4

34. As per the FACT study, Diamicron MR 60 reduces HbA1c by -1.9% in 6 months at the dosage of 1.5 to 2 tablets With least hypoglycemia as well as no weight gain Findings of FACT study

35. Clinical Evidences on use of OAD in Ramadan

36. Prof. Hajera Mahtab Professor Emeritus Ex-Director Clinical Services, Research & Academy Dhaka, Bangladesh Prof. Abdul Hamid Zargar Professor & Head Department of Endocrinology SK Institute of Medical Sciences Srinagar, India Prof. Abdul Basit Director & Head of the Department Baqai Institute of Diabetology & Endocrinology Baqai Medical University Karachi, Pakistan RESEARCH ANALYSIS

37. Sulphonylureas in the management of type 2 diabetes during the fasting month of Ramadan Among the 2 nd generation SUs considering efficacy and safety, which one is more suitable during Ramadan Sulfonylureas as a first line used by majority of patients Many of Muslim type 2 diabetic patients fast in Ramadan Alteration of energy intake, physical activity & drug pattern associated with greater risk of hypoglycemia & ketoacidosis

38. Among the two once daily Sulphonylureas hypoglycemia is -50% less with Diamicron MR60 than glimepiride Diamicron MR Glimepiride

39. Diamicron MR60 is associated with less hypo and less CV events than glimepiride

40. Objective: To evaluate the efficacy & safety of Diamicron MR60 at the dosage of 1 tablet in Ramadan Participating countries: Bangladesh, India & Pakistan

41. Prof. Hajera Mahtab BIHS Prof. Zafar A Latif BIRDEM Prof. Tofail Ahmed BIRDEM Prof. M A Mannan DMCH Prof. Md. Farid Uddin BSMMU Dr. Saghir Abdur Rahim BIRDEM Dr. Sarker M Saiful Islam MEDINOVA Dr. ABM Rahmatullah HCDP- Jurain Dr. Sufia Khatun NHN- Mirpur 10 Dr. Umme Sadia Mili NHN- Darus Salam Dr. Md. Wahiduzzaman NHN- Darus Salam Dr. MA Sabur DAB- Khulna THE RAMADAN STUDY GROUP- BANGLADESH

42. Inclusion Criteria: Newly diagnosed type 2 diabetic patients: start with 60 mg Patients uncontrolled with 1 tablets of Diamicron MR/ Gliclazide 80/MR or 1 mg of Glimepiride : up-titrate to 60 mg Diamicron MR60 Patients well controlled on 60 mg of Diamicron MR60 Patients well controlled on 2 tablets of Gliclazide 80/MR or 2 mg of Glimepiride : switched to 60 mg of Diamicron MR60 THE RAMADAN STUDY

43. Total number of patients: 136 fasting type 2 diabetic (35 Bangladeshi+ 50 Indian+ 51 Pakistani) Duration: 90 days (45 before Ramadan+ 30 Ramadan+ 15 after Ramadan) Result: - Around 1% (0.8%) HbA1c reduction within 3 months - 3.7% hypoglycemia before, 2.2% during & 1.5% after Ramadan THE RAMADAN STUDY

44. Conclusion: Diamicron MR60 maintains tight glycemic control, safely before, during & after Ramadan

45. Objective: To compare the incidence of symptomatic hypoglycemia in fasting Muslim patients with type 2 diabetes treated with DPP-4 inhibitor or SU during Ramadan. Middle East

46. Conclusion: Risk of hypoglycemia is lowest with Diamicron MR60, whereas double with glimepiride

47. IDF guideline (October’12) recommends sulfonylurea to initiate treatment irrespective of BMI But all sulfonylureas do not provide same outcome Therefore, selection of sulfonylurea is a major issue to be considered before initiating treatment Take home messages

48. As per the clinical evidences Diamicron MR 60 provides effective glycemic control irrespective of BMI with least risk of hypo & without weight gain significantly reduces vascular complications ensures cardiovascular protection unlike glimepiride , also better than metformin preserves beta cell through anti-oxidant properties Take home messages

49. Acknowledgement Prof. Md. Fariduddin Asso . Prof. M A Hasanat Dr. Mashfiqul Hasan Dr. Yasmin Aktar Sponsoring body

50. Thank you