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