SULFONYLUREA: OAD agentMode of action:• Sulfonylureas act directly on the β - cells of the islets ofLangerhans to stimulate insulin secretion• They enter the β – cell and bind to the cytosolic surface of thesulfonylurea receptor 1• Binding of a sulfonylurea closes the K + ATP channel, reducingthe efflux of potassium enabling membrane depolarization• Localized membrane depolarization opens adjacent voltage -dependent L - type calcium channels• Increasing calcium influx and raising the cytosolic freecalcium concentration• Mediate the exocytotic release of insulin granules
Classification• Divided into first and second generationagents• In general, the second-generation agents– Are more potent– Have fewer adverse effects and drug-druginteractions
Extended release preparations• Extended-release glipizide and glimepiride arepreferred agents because- they can be given once daily- involve a relatively low risk ofhypoglycemia-low weight gain
Modified release preparations• A “ modified release ” (MR) formulation ofgliclazide has been introduced for once - dailydosing• Interestingly, the 30 mg preparation ofgliclazide MR gives similar efficacy to 80 mg ofunmodified gliclazide and reduces risk ofsevere hypoglycemia
Target HbA1c <7% instead of <6.5%Evidence based alternative approachSU as 1st line, irrespective of BMITZD & DPP-4 inhibitor are 3rd optionWhat’s NEW in the treatmentalgorithm of IDF Guideline 2012?
Which SU to choose-gliclazide 80,glimepiride or the newDiamicron MR 60??
One of the largest clinical studiesever performed in type 2 diabetesN Engl J Med. 2008;358:2560-2572
More than 11,000 type 2 diabeticpatients from 20 countries worldwide4 Asian countries- China, India, Malaysia & PhilippinesN Engl J Med. 2008;358:2560-2572
Aim of the studyWhat benefits can be gained fromintensive glycemic control (HbA1c≤6.5%) versus standard control?N Engl J Med. 2008;358:2560-2572
Strategy & TimelineMean duration 5 yearsStrategy: treatment initiation with 60 mgDiamicron MR, increase up to 120 mg then addother therapyJune2001January2002January2003January2004January2005January2006January2007January2008Blood glucose lowering comparisonRecruitment periodN Engl J Med. 2008;358:2560-2572
Results & OutcomesN Engl J Med. 2008;358:2560-2572. Diabetes Care 32:2068–2074, 2009. Diabetes Res Clin Pract. 2010;89:126-133.
Prof. Hajera MahtabProfessor EmeritusEx-DirectorClinical 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, PakistanRESEARCH ANALYSIS
Sulphonylureas in the management of type 2 diabetes during the fastingmonth 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 patternassociated with greater risk of hypoglycemia & ketoacidosis
Among the two once daily Sulphonylureas hypoglycemia is -50% lesswith Diamicron MR60 than glimepirideDiamicron MR Glimepiride
Diamicron MR60 is associated with less hypo andless CV events than glimepiride
Objective:To evaluate the efficacy &safety of Diamicron MR60at the dosage of 1 tabletin RamadanParticipating 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- KhulnaTHE 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 mgDiamicron MR60 Patients well controlled on 60 mg of Diamicron MR60 Patients well controlled on 2 tablets of Gliclazide 80/MR or 2mg of Glimepiride: switched to 60 mg of Diamicron MR60THE 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 afterRamadan)Result:- Around 1% (0.8%) HbA1c reduction within 3 months- 3.7% hypoglycemia before, 2.2% during & 1.5% afterRamadanTHE RAMADAN STUDY
Objective:To compare the incidence ofsymptomatic hypoglycemia infasting Muslim patients with type2 diabetes treated with DPP-4inhibitor or SU during Ramadan.
Conclusion:Risk of hypoglycemia is lowest with Diamicron MR60, whereasdouble with glimepiride
IDF guideline (October’12) recommendssulfonylurea to initiate treatment irrespective ofBMIBut all sulfonylureas do not provide sameoutcomeTherefore, selection of sulfonylurea is a majorissue to be considered before initiating treatmentTake home messages
As per the clinical evidences Diamicron MR 60 provides effective glycemic control irrespectiveof BMI with least risk of hypo & without weight gain significantly reduces vascular complications ensures cardiovascular protection unlikeglimepiride,also better than metformin preserves beta cell through anti-oxidantpropertiesTake home messages
Acknowledgement• Prof. Md. Fariduddin• Asso. Prof. M A Hasanat• Dr. Mashfiqul Hasan• Dr. Yasmin Aktar• Sponsoring body