GLICLAZIDE MR IN THE MANAGEMENT OF TYPE 2 DM
Dr. Nazma AkhtarResident phase B
Department of EndocrinologyBSMMU
3/28/2013 3
3/28/2013 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
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
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
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
Þ Target HbA1c <7% instead of <6.5%
Þ Evidence based alternative approach
Þ SU as 1st line, irrespective of BMI
Þ TZD & DPP-4 inhibitor are 3rd option
What’s NEW in the treatmentalgorithm of IDF Guideline 2012?
Which SU to choose-gliclazide 80, glimepiride or the new Diamicron MR 60?
?
One of the largest clinical studiesever performed in type 2 diabetes
N Engl J Med. 2008;358:2560-2572
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
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
Strategy & Timeline
Mean duration 5 years
Strategy: treatment initiation with 60 mg Diamicron MR, increase up to 120 mg then
add other therapyJune 2001
January 2002
January 2003
January 2004
January 2005
January 2006
January 2007
January 2008
Blood glucose lowering comparisonRecruitment period
N Engl J Med. 2008;358:2560-2572
Results & Outcomes
N Engl J Med. 2008;358:2560-2572. Diabetes Care 32:2068–2074, 2009. Diabetes Res Clin Pract. 2010;89:126-133.
Reduces HbA1c ≤7% within 6 months
N Engl J Med. 2008;358:2560-2572
Reduces HbA1c by more than 4%unlike other SU
N Engl J Med. 2008;358:2560-2572
Reduces HbA1c ≤7% irrespective of BMI
N Engl J Med. 2008;358:2560-2572
Lowest episodes of hypoglycemiacompared 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.
Lowest hypoglycemiacompared to DPP4-inhibitor
Int J Clin Pract. 2011;65:1132-1140. Curr Med Res Opin 2012; 28:1–8
Middle East
India & Malaysia
MORE
EVIDENCESMORE
EVIDENCES
Weight neutral unlike other SU
N Engl J Med. 2008;358:2560-2572
5 YEARS
DATA5 YEARS
DATA
Significantly reduces combinedmicro & macro vascular complications
N Engl J Med. 2008;358:2560-2572
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
EVIDENCESMORE
EVIDENCES
Better CV protectionthan Metformin & glimepiride
Eur Heart J. 2011 Aug;32(15):1900-8.
MORE
EVIDENCESMORE
EVIDENCES
Reduces End-stage Kidney Diseaseunlike any other OAD
Diabetologia. 2011;54(suppl 1):S23.
RECENT
ANALYSISRECENT
ANALYSIS
Reduces Beta cell apoptosisunlike glimepiride
Metabolism. 2008;57:1038-1045.
MORE
EVIDENCESMORE
EVIDENCES
Prolongs insulin free period
Diabetes Res Clin Pract. 2005;70:291-297.
While maintains HbA1c <7% for 14.5 years!!
FACT: EFficacy & tolerAbility of DiamiCron MR60
at the dosage of 1.5 to 2 tablets at breakfast over
Bangladeshi Type 2 diabetic patients
A clinical study conducted by Bangladeshi clinicians over
Bangladeshi type 2 diabetic patients
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
Findings
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
Efficacy: Reduction of HbA1c (Total Patients)
5
5.5
6
6.5
7
7.5
8
8.5
9
Base line After 6 months
-1.9% HbA1c reduction within 6 months
-1.9%
n= 3598.9%
7.0%
Tolerability
Only 1.0% hypoglycemia was found!!
Baseline After 6 months
Change
Weight (kgs)
63.7 63.3 -0.4
Þ 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
Þ With least hypoglycemia as well as no
weight gain
Findings of FACT study
Clinical Evidences on use
of OAD in Ramadan
Prof. Hajera MahtabProfessor EmeritusEx-Director Clinical Services, Research & AcademyDhaka, Bangladesh
Prof. Abdul Hamid ZargarProfessor & HeadDepartment of EndocrinologySK Institute of Medical SciencesSrinagar, India
Prof. Abdul BasitDirector & Head of the DepartmentBaqai Institute of Diabetology & EndocrinologyBaqai Medical UniversityKarachi, Pakistan
RESEARCH ANALYSIS
Sulphonylureas in the management of type 2 diabetes during the fasting month of Ramadan
Among the 2nd 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
Among the two once daily Sulphonylureas hypoglycemia is -50% less with Diamicron MR60 than glimepiride
Diamicron MR Glimepiride
Diamicron MR60 is associated with less hypo and less CV events than glimepiride
Objective:
To evaluate the efficacy & safety of Diamicron MR60 at the dosage of 1 tablet in Ramadan
Participating countries:
Bangladesh, India & Pakistan
Prof. Hajera Mahtab BIHSProf. Zafar A Latif BIRDEMProf. Tofail Ahmed BIRDEMProf. M A Mannan DMCHProf. Md. Farid Uddin BSMMUDr. Saghir Abdur Rahim BIRDEMDr. Sarker M Saiful Islam MEDINOVADr. ABM Rahmatullah HCDP- JurainDr. Sufia Khatun NHN- Mirpur 10Dr. Umme Sadia Mili NHN- Darus SalamDr. Md. Wahiduzzaman NHN- Darus SalamDr. MA Sabur DAB- Khulna
THE RAMADAN STUDY GROUP- BANGLADESH
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
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
Conclusion:Diamicron MR60 maintains tight glycemic control, safely before, during & after Ramadan
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
Conclusion:Risk of hypoglycemia is lowest with Diamicron MR60, whereas double with glimepiride
Þ IDF guideline (October’12) recommends
sulfonylurea to initiate treatment
irrespective of BMI
Þ But all sulfonylureas do not provide same
outcome
Þ Therefore, selection of sulfonylurea is a
major issue to be considered before
initiating treatment
Take home messages
Þ 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
Acknowledgement
• Prof. Md. Fariduddin• Asso. Prof. M A Hasanat• Dr. Mashfiqul Hasan• Dr. Yasmin Aktar• Sponsoring body
Thank you
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