This document discusses the novelty of gliclazide MR in assessing patient needs compared to other sulfonylureas and newer drug classes. It summarizes data from major trials like ADVANCE showing gliclazide MR's efficacy in rapidly reaching glycemic targets regardless of baseline levels, maintaining long-term control for up to 15 years, and protecting kidney function even in advanced CKD patients. It also has a long history of safe use and is one of the most cost-effective oral hypoglycemic agents according to the WHO.

1. THE NOVELTY IN ASSESSING
THE PATIENT’S NEEDS
Prof Hanan Gawish, MD,PhD
Diabetes and Endocrinology Unit, Mansoura Uni
Chair of the Egyptian Society of Diabetic Foot

2. Novelty may be said of some very old places, as of
some very old books, that they are destined to be
forever new.
The nearer we approach them…..the more we
study them, the more we have yet to learn.
This is true of many ancient civilization but of no
place it is so true as of ……..Egypt.
Amelia Blanford Edwards

4. AGENDA
 Novelty among other Sulfonylureas

5.  11,140 type 2 diabetics.
 Average age is 66 years.
 8 years of Diabetes.
 32% had diagnosed
CVD.
 10% had microvascular
complications
 CVD risk factors
[Lipids, BP, smoking or
obesity].
ADVANCE
N=11,140
The ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572.

6. Randomized treatment
Intensive
(n=4828)
Standard
(n=4741)
Gliclazide MR
Other Sulfonylureas
92%
0%
 0%
59%
Metformin 74% 67%
Thiazolidinediones 17% 11%
Acarbose 19% 13%
Glinides 1% 3%
Insulin 40% 24%
ADVANCE
N=11,140

7. TIGHT GLYCEMIC CONTROL MAINTAINED ON LONG TERM
ADVANCE collaborative group. N Engl J Med 2008; 358:2560-72

8. COMBINED PRIMARY OUTCOMES
MAJOR MACRO OR MICROVASCULAR EVENT
ADVANCE
N=11,140
-10%
The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.

9. MAJOR MICROVASCULAR EVENTS
ADVANCE
N=11,140
-14%
The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.

10. GLICLAZIDE REDUCES MORTALITY
Cardiovascular death 253 289 12% (-4 to 26)
All deaths 498 533 7% (-6 to 17)
Non-cardiovascular death 245 244 0% (-20 to 16)
Number of patients with event
Intensive Standard
(n=5,571) (n=5,569)
Relative risk
reduction (95%CI)
Favors
Intensive
Favors
Standard
Hazard ratio
0.5 1.0 2.0
Cardiovascular Mortality
-12%
P=0.12
ADVANCE
N=11,140
The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.

12. ACCORD
N=10,251
New England Journal of Medicine. N Engl J Med. 2008;358:2545-2559.

13. New England Journal of Medicine. N Engl J Med. 2008;358:2545-2559.
7.5%
6.4%
6.4 in the intensive group Vs. 7.5 in the Standard
ACCORD
N=10,251

15. VADT
N=1,791
Duckworth et al, New eng J Med 2008; ahead of print
 Metformin (BMI >27)
or Glimepiride (BMI
<27).
 Rosiglitazone.
 Insulin.
 Other oral agents.
8.4%
6.9%

16. 1. N Engl J Med. 358(2008)2545-59
2. N Engl J Med. 360(2009)129-39
ACCORD1 VADT2
Number 10,251 1,791
Primary CVD
endpoint
 10% (p=0.16)  13% (p=0.12)
Mortality
(overall)
 22% (p=0.04)  6.5% (p=NS)
CV mortality  39% (p=0.02)  25% (p=NS)
Reduction of CV disease risk in type 2 diabetes:
lessons learned from ACCORD and VADT trials

17. IDF
2012
ACCORD
Guidelines asked to assess the cardiac safety for all the new drugs
EVIDENCE-BASED MEDICINE
SHAPED THE NEW IDF ALGORITHM

18. THE LOWEST RISK OF HYPOGLYCEMIA
AMONG SUS STRATEGIES
Reached targets below 7%

19. Accord ADVANCE VADT
Severe hypoglycemia in
intensive arm [%
participants with ≥ 1
episodes]
16.2% 2,7% 21.2%
Lowest rates of hypoglycemia
A position statement of ADA, ACC and AHA. Diabetes Care, volume 32; 1, January 2009.

21. CONTROL Group. Diabetologia. 2009, August 6. Epub ahead of print.
ADVANCE TRIAL: STRICT WEIGHT
NEUTRALITY BELOW 7%
2 tablets

22. ADVANCE TRIAL: STRICT WEIGHT
NEUTRALITY BELOW 7%

24. 1-NO ACTIVE METABOLITES
1. Gribble FM. Diabetologia. 1999;42:845-848.
2. Gribble FM. Diabetes. 1998;47:1412-1418. 3. Song DK. Br J Pharmacol. 2001;133:193-199.

25. 2-
REVERSIBILITY
1. Gribble FM. Diabetologia. 1999;42:845-848.
2. Gribble FM. Diabetes. 1998;47:1412-1418. 3. Song DK. Br J Pharmacol. 2001;133:193-199.
Why?

26. 3- INSULIN SECRETION
1. Gribble FM. Diabetologia. 1999;42:845-848.
2. Gribble FM. Diabetes. 1998;47:1412-1418. 3. Song DK. Br J Pharmacol. 2001;133:193-199.
Why?

27. Gregorio F et al. Diabetes Res Clin Prac. 1992;18:197-206.
3- INSULIN SECRETION
Why?

28. 4- ANTI-OXIDANT
PROPERTIES
Sawada F et al. Metabolism. 2008;57:1038-1045.
Why?

29. Canadian therapeutic algorithm for
management of patients with T2D 2013)

30. NHG Standard on T2DM (third edition)
Deutsch guidelines for T2DM (2013).

33. SLOVAK therapeutic algorithm for
management of patients with T2D
(Slovak diabetology society,
June 2015)

34. AGENDA
 Novelty among other Sulfonylureas
 Novelty among other new groups

35. NOVELTY AMONG OTHER GROUPS
sulphonylureas
TZDs
DPP-4
inhs
Glinides
GLP-1
agonists
SGLT2

36. AGENDA
 Novelty among other Sulfonylureas
 Novelty among other new groups:
 Efficacy

37. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

38. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

39. 1. DIAGONAL study. Congress of the Federation of the International Danube Symposia on Diabetes Mellitus,2012. Hungary, Budapest. Abstract. Available at
http://fid2012.shp.hu/hpc/web.php?a=fid2012&o=abstracts_8qQs 2. Satoh J et al. Diabetes Res Clin Pract. 2005;70:291-297.
PATIENTS STARTED WITH GLICLAZIDE 60 MR 1-2 TABLETS.
RAPID GLYCEMIC CONTROL

40. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

41. The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.
STRONG REDUCTION WHATEVER THE
HBA1C BASELINE

42. INITIAL FIXED-DOSE COMBINATION THERAPY
WITH SITA+ MET VS METFORMIN MONO-THERAPY:
CHANGE FROM BASELINE IN HBA1CAT WEEK 18
Diabetes, Obesity and Metabolism 13: 644–652, 2011.

43. MBANYA, JUNE.2015
IDF-WPR abstract: Singapore, 21-24 November 2014,prof.mbanya

44. ADA , JUNE.2014
Hassanein et al. Vascular Health & Risk Management, 10(2014)319-26

45. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

46. The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.
WHATEVER THE BMI

47. The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.
WHATEVER THE DURATION OF
DIABETES

48. The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.
WHATEVER THE AGE

49. The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.
WHATEVER THE BASELINE
TREATMENT

50. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

51. % OF PATIENTS CONTROLLED BELOW
7%
*Esposito et al. Acta Diabetol. 2014;51:305-311.

52. HIGHEST
% OF PATIENTS CONTROLLED BELOW
7%
The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.

53. NOVELTY AMONG OTHER GROUPS
NOVELTY IN EFFICACY
1.RAPID .
2.REACHING THE TARGET WHATEVER THE BASELINE.
3.SUITABLE FOR MOST OF THE PATIENTS.
4.CONTROL RATE.
5.MAINTAINED CONTROL.

54. Objectives: To evaluate glycaemic durability with (DPP-4)
inhibitors in type 2 diabetes.
Interventions: (sitagliptin, vildagliptin, saxagliptin,
linagliptin and alogliptin).
Inclusion: We screened 12 trials in 14,829 participants.
In conclusion, the analysis of 12 randomized trials with duration
up to 108 weeks suggests that the effect of DPP-4 inhibitors on
HbA1c decreases after the first year of treatment.
Downloaded from bmjopen.bmj.com on June 18, 2014 - Published by group.bmj.com

56. Maintained CONTROL FOR 5 YEARS IN
ADVANCE
The ADVANCE Collaborative Group. Action in Diabetes and Vascular disease: Preterax and Diamicron MR Controlled Evaluation. IDF Annual Meeting.2009.

57. EASD,SEPT,2014
THE EARLY START WITH GLICLAZIDE 60
MR DECREASES THE NEED FOR INSULIN.
Gliclazide 60 MR
2 tabs
120 mg
DOI: 10.1056/NEJMoa1407963

58. Maintained for 15 years if compared with
other SUs
Satoh J et al. Diabetes Res Clin Pract. 2005;70:291-297.
2 tabs
120 mg

59. AGENDA
 Novelty among other Sulfonylureas
 Novelty among other new groups:
 Efficacy
 CKD Patients

62. WHY DIAMICRON 60 MR is preferred
without dose adjustment ?

63. 1. UKPDS Group (33). Lancet. 1998;352:837-853. 2. VADT Investigators. N Engl J Med. 2009;360:129-139. 3. Ismail-Beigi F et al. Lancet. 2010;376:419-
430. 4. ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560-2572. 5. Zoungas S et al. Diabetologia. 2011;54(suppl 1):S23.
ADVANCE TRIAL:
UNIQUE KIDNEY PROTECTION IN ALL THE STAGES

64. AGENDA
 Novelty among other Sulfonylureas
 Novelty among other new groups:
 Efficacy
 CKD Patients
 Having long record in the market

66. AGENDA
 Novelty among other Sulfonylureas
 Novelty among other new groups:
 Efficacy
 CKD Patients
 Having long record in the market
 Cost effectiveness

67. WHO Model List of Essential Medicines 18th list. Accessed on May 2015
NOVELTY IN COST EFFECTIVENESS
WHO
August 2015
Criteria for Selection of Essential Medicines: Essential medicines are selected with due
regard to disease prevalence, evidence on
efficacy , safety, and comparative cost-effectiveness

68. Conclusion:
Treatment decision should be based on :
• Practice (Results and Durability)
• Evidence ( Efficacy and Safety)
• Cost Effectiveness