AS PER SAFES STATEMENT

1. DR. P. RAMANATHAN.M.D,.
SENIOR CONSULTANT PHYSICIAN,
RAILWAY HOSPITAL,
MADURAI.

3. INTRODUCTION
• T2DM is pandemic , characterised by increasing
complexity of management and raising concerns
over safety and cost of medicine.
• Globally the prescription patterns have changed
with the introduction of new agents.
• Majority of the population is treated with OADs
either mono or combo therapy.
• SUs account for 20 percent of newly initated
drugs.
• This initiative by SAFES aims to encourage
rational, smart and safe prescription of Sus.

6. 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

8. • K ATP channels present in extra pancreatic tissues also
but with different SUR subunit.
• Effect of SUs on K ATP in different tissues vary.
• Affinity, selectivity and reversibility of different SUs are
different .
• Depends on the sulfonyl and benzamido moieties.
• Gliclazide has no benzamido moiety will bind only with
sulfonyl site of SUR and hence has pancreas selectivity.

9. Glimepride and gliclazide
• glimepride…different kDa binding site on
SUR..low affinity, higher rate of association
and dissociation,.. Lower inhibition of KATP
…low risk of hypoglycemia…augment both
first and second phase of insulin secretion..
• Gliclazide..only SU not to bind to Epac 2
moiety of SUR which is a stimulatig factor for
insulin exocytosis and hence low
hypoglycemic risk.

20. Reduces Beta cell apoptosis
unlike glimepiride
Metabolism. 2008;57:1038-1045.

21. Prolongs insulin free period
Diabetes Res Clin Pract. 2005;70:291-297.
While maintains HbA1c <7% for 14.5 years!!

25. Effect of Exenatide, Sitagliptin, or
Glimepiride on b-Cell Secretory
Capacity in Early Type 2 Diabetes
Diabetes Care 2014;37:2451–2458 |
DOI: 10.2337/dc14-0398
Lalitha Gudipaty,1 Nora K. Rosenfeld,1
Carissa S. Fuller,1 Robert Gallop,2
Mark H. Schutta,1 and Michael R. Rickels1
Diabetes Care Volume 37, September 2014

26. • GLP-1 analogues and DPP4 inhibitors have been shown
to increase both insulin production and secretion and
so were expected to have a positive effect on
functional β-cell mass.
• A sulfonylurea was selected as an active comparator
insulin secretogogue rather than a placebo to provide
an agent that would control glycemia by increasing
insulin secretion without affecting the functional β-cell
mass.
• Since sulfonylureas induce insulin secretion without
affecting production, they have been theorized to
deplete insulin stores

27. Subject characteristics over the 6-month study period.
Gudipaty L et al. Dia Care 2014;37:2451-2458
Copyright © 2014 American Diabetes Association, Inc.

28. • Six months of treatment with glimepiride was
effective in decreasing capillary blood glucose
and lowering HbA1c without producing
hypoglycemic episodes or weight gain with
careful dose titration

29. CONCLUSIONS
• After 6 months of treatment, exenatide or
sitagliptin had no significant effect on
functional β-cell mass as measured by β-cell
secretory capacity, whereas glimepiride
appeared to enhance β- and α-cell secretion

30. WEIGHT GAIN

32. Weight neutral unlike other SU
N Engl J Med. 2008;358:2560-2572

34. 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.

35. Lowest hypoglycemia
compared to DPP4-inhibitor
Int J Clin Pract. 2011;65:1132-1140. Curr Med Res Opin 2012; 28:1–8
Middle East 
 India & Malaysia

39. Better CV protection
than Metformin & glimepiride
Eur Heart J. 2011 Aug;32(15):1900-8.

40. 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.