GLICLAZIDE MR IN THE

MANAGEMENT OF TYPE 2 DM

Dr. Nazma Akhtar

Resident phase B
Department of Endocrinology
BSMMU
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
 What’s NEW in the treatment
algorithm of IDF Guideline 2012?

Target HbA1c <7% instead of <6.5%

Evidence based alternative approach

SU as 1st line, irrespective of BMI

TZD & DPP-4 inhibitor are 3rd option

?
Which SU to choose-
gliclazide 80,
glimepiride or the new
Diamicron MR 60?
 One of the largest clinical studies
ever 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

Strategy: treatment initiation with 60 mg

Diamicron MR, increase up to 120 mg then add
other therapy
June January January January January January January January
2001 2002 2003 2004 2005 2006 2007 2008

Recruitment period Blood glucose lowering comparison

Mean duration 5 years

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 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.

 Lowest hypoglycemia
compared to DPP4-inhibitor

Middle East

India & Malaysia

Int J Clin Pract. 2011;65:1132-1140. Curr Med Res Opin 2012; 28:1–8
 Weight neutral unlike other SU

N Engl J Med. 2008;358:2560-2572

 Significantly reduces combined
micro & 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.

 Better CV protection
than Metformin & glimepiride

Eur Heart J. 2011 Aug;32(15):1900-8.

 Reduces End-stage Kidney Disease
unlike any other OAD

Diabetologia. 2011;54(suppl 1):S23.

 Reduces Beta cell apoptosis
unlike glimepiride

Metabolism. 2008;57:1038-1045.
 Prolongs insulin free period

While maintains HbA1c <7% for 14.5 years!!

Diabetes Res Clin Pract. 2005;70:291-297.
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)

9 n= 359
8.5
8.9% -
8 1.9%
7.5

7
7.0%
6.5

5.5

5
Base line After 6 months

-1.9% HbA1c reduction within 6 months

 Tolerability

Only 1.0% hypoglycemia was found!!

Baseline After 6 Change

months
Weight (kgs) 63.7 63.3 -0.4
 Findings of FACT study

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
Clinical Evidences on use of
OAD in Ramadan
 RESEARCH ANALYSIS

 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
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
THE RAMADAN STUDY GROUP- BANGLADESH

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

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
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.
Conclusion:
Risk of hypoglycemia is lowest with Diamicron MR60, whereas
double with glimepiride
 Take home messages
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
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
 Acknowledgement
• Prof. Md. Fariduddin
• Asso. Prof. M A Hasanat
• Dr. Mashfiqul Hasan
• Dr. Yasmin Aktar
• Sponsoring body
Thank you