Sulfonylureas were discovered by the french chemist Marcel Janbon and co-workers during World War II , who were studying sulfonamide antibiotics and discovered that the compound sulfonylurea induced hypoglycemia in animals.

1. Translating evidence into patients’ benefits
By: Abbas Oraby

3. History
Sulfonylureas were discovered
by the french chemist Marcel
Janbon and co-workers during
World War II
, who were studying
sulfonamide antibiotics and
discovered that the compound
sulfonylurea induced
hypoglycemia in animals.

4. History
Janbon convinced a medical
colleague, August Loubatieres, to
try it on his diabetic patients. The
drug triggered a fall in these
patients' blood sugars.
Experiments by Loubatieres and
others, with animals and with
isolated pancreas, later revealed
that the sulfonylurea stimulated
pancreas cells to release insulin.

5. History
Sulfonylureas were the first
widely used oral anti-
hyperglycaemic medications.
Many types of these pills have
been marketed but not all remain
available.
Until 1995, sulfonylureas were
the only class of medications
available for the treatment of
patients with type 2 diabetes
besides insulin.

6. Drugs in this class
Sulfonylureas were the first widely used oral anti-hyperglycaemic
medications. Many types of these pills have been marketed but not all
remain available.

7. MECHANISMS OF ACTION OF SUs

8. Insulin release
•
It involves 3 main steps :
1. Translocation of insulin granules.
2. Docking of insulin granules.
3. Fusion of insulin granules.
8

9. Translocation of insulin granules
•
Two essential components of
the cytoskeletal elements :
1. Microtubules (formed of tubulin
subunits).
2. Microfilaments (Actin + Myosin).
9

10. Microtubules form a network radiating from the
perinuclear region outwords
.
The framework provides
the mechanical pathway
along which secretory
granules move toward the
exocytic sites close to the
plasma membrane.
It gives the way but not the force
10

11. The motive force to propel granules along the
microtubules is provided by the interaction between :
Filamentous Phosphorylated
actin + myosin
ATP Ca+
Granule transport
It gives the force but not the way
11

12. Ca+ is essential for almost all steps
involved in insulin release, thus factors
increasing intracellular Ca+ will augment
insulin release.Mechanisms involved in
increasing intra-cytoplasmic Ca+ :
 Ca-influx from outside.
 Inhibition of Ca-reuptake by Ca++ Store
intracellulas stores. x
 Increased Ca-sensitivity.
12

13. Increased intracellular Ca+ is essential for
granules translocation and fusion hence release of
insulin.
ATP-sensitive Voltage-gate Ca
Glucose
K+ channel channel
6
GLUT2 X
Fusion
K retention 4
Glucose 3
Depolarization Ca+
2
Glucokinase 1 5
G-6-P ATP Translocation
Each B-cell contains up to 500 Ca channels 13

14. Mechanisms of action cont.
• The rise in intracellular calcium leads to
increased fusion of insulin granules with the
cell membrane, and therefore increased
secretion of (pro)insulin.
• There is some evidence that sulfonylureas
also sensitize β-cells to glucose, that they
limit glucose production in the liver, that they
decrease lipolysis and decrease clearance of
insulin by the liver.

15. Insulin Secretion (Glimepiride)
Glimepiride binds to the 65 kDa subunit of the sulfonylurea
receptor; glibenclamide binds to the 140 kDa subunit

16. Therapeutic actions
Pancreas
Sulfonylurea +
Impaired glimepiride
Insulin secretion
Insulin
– resistance
Increased Decreased
glucose glucose
production Hyperglycaemia uptake
Liver Muscle
Metformin
16

17. Attributes of sulfonylureas
How they work Enhance insulin secretion
Expected HbA1c
1 to 2%
reduction
Adverse events Hypoglycemia* (but severe episodes are infrequent)
Weight effects ~ 2 kg weight gain common when therapy initiated
CV effects None substantiated by UKPDS or ADVANCE study
* Substantially greater risk of hypoglycemia with chlorpropamide and glibenclamide (glyburide) than other
second- generation sulfonylureas (gliclazide, glimepiride, glipizide) 17
Adapted from Nathan DM, et al. Diabetes Care 2009;32:193-203.

18. IDF Global Guideline for Type 2 Diabetes
Diagnosis
Lifestyle intervention then metformin
HbA1c ≥6.5 %
Add sulfonylurea
HbA1c ≥6.5 % HbA1c ≥6.5 %
*Alternatively, start Add thiazolidinedione* Add insulin
thiazolidinedione before
sulfonylurea,
and sulfonylurea later. HbA1c ≥7.5 % HbA1c ≥7.0 %
Start insulin intensify insulin
Meal-time + basal insulin + metformin ± thiazolidinedione
IDF. Global Guideline for Type 2 Diabetes. 2005

21. ADA and EASD algorithm for the management
of type 2 diabetes
Tier 1: Well validated therapies
Lifestyle and
At Lifestyle and met + intensive
diagnosis: met + basal insulin
Lifestyle insulin
+
metformin Lifestyle and
met + SUa
Step 1 Step 2 Step 3
Tier 2: Less well validated therapies
Lifestyle and
met + pio Lifestyle and met
No hypoglycaemia
Oedema/CHF
+ pio + SUa
Bone loss
Lifestyle and met
+ GLP-1 agonistb Lifestyle and
No hypoglycaemia
Weight loss
met + basal insulin
Nausea/vomiting
Reinforce lifestyle interventions every visit and check HbA1C every
3 months until HbA1C is <7% and then at least every 6 months.
The interventions should be changed if HbA1C is ≥7%
SUs other than glybenclamide (glyburide) or chlorpropamide. bInsufficient clinical use to be confident regarding safety.
a
Met=metformin; Pio=pioglitazone; SU=sulfonylurea
Nathan et al., Diabetes Care 2008 [Epub]

23. Type 2 Diabetes is a Dual Problem
Schematic Representation of the Natural Progression of
Type 2 Diabetes
INSULIN
RESISTANCE
FPG/PPG
HbA1c↑
INSULIN
SECRETION
Normal IGT Type 2
Adapted from Type 2 Diabetes BASICS. Minneapolis, MN: International Diabetes Center; 2000

24. Glimepiride : Dual Mechanism for Dual Problem
INSULIN
RESISTANCE
FPG / PPG
HbA1C
INSULIN
SECRETION
Normal IGT Type 2
Graphic interpretation based on:
24
Muller G, et al. Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37; Massi-Benedetti M. Clin Ther 2003; 25(3): 799-816

25. Unique Dual Mode of Action
Action on insulin Action on insulin
secretion resistance
Glimepiride1 ► ►
Conventional
Sulfonylureas1 ► -
Glinides1,2 ► -
Biguanides1,3-5 - ►
Glitazones1,6 - ►
1
Medical Management of Type 2 Diabetes. 4th ed. Alexandria, Va: American Diabetes Association; 1998:1-139; 2Goldberg 1998, et al. Diabetes Care
21:1897-1903; 3Bell & Hadden. Endocrinol Metab Clin 1997;26:523-37; 4De Fronzo, et al. N Engl J Med 1995;333:541-9; 5Bailey & Turner. N Engl J Med
1996;334:574-9; 6Henry. Endocrinol Metab Clin 1997;26:553-73

26. Acting on Both Phases of Insulin Secretion
GlimepirideThe only sulfonylurea to treat
fasting and postprandial hyperglycemia
First and second phase insulin secretion
before and after treatment with Glimepiride
p=0.02
100
Incremental plasma insulin
Euglycemic and
hyperglycemic clamp
studies in 11 obese
patients with T2DM
with good glycemic
p=0.04 + Glimepiride
control before and after
50 4 months treatment
with Glimepiride to
assess effect of
(pmol/L)
+Glimepiride Glimepiride on insulin
secretion
0
First Phase Second Phase
Insulin secretion
Before treatment After Glimepiride treatment
Korytkowski M et al. Diabetes Care 2002; 25(9):1607-11.

27. 2nd Action: Extra-Pancreatic
The extrapancreatic effect of Glimepiride
Rate limiting step for glucose
utilization is glucose uptake via GLUT4
transporter
• Glimepride↑ translocation of GLUT4
transporters from low-density
microsomes to plasma membrane
of insulin-resistant fat and muscle
cells
Glimepiride appears to ↑ peripheral
glucose uptake and to mimic the
action of insulin
27 Müller & Wied. Diabetes. 1993;42: 1852-1867

28. Glimepiride Controls Glycemia with Less Insulin Secretion
• For an equivalent glycemic effect, Glimepiride induces a lower
secretion of insulin
Mean variation of insulin and Mean ratio between increased level of
glycemia over a 36-h period insulin and reduced glycemia
Sulfonylureas tested in
fasted male beagle dogs
3 to determine ratios of
Insulinemia
2
Ratio mean plasma insulin
release/ blood glucose
(µU/mL)
1 decrease
0.20
n=16
0
Glimepiride Glibenclamide Gliclazide Glipizide 0.15
0 n=13
0.10
5 n=14
variation (%)
10 0.05 n=16
Glycemic
15
0.00
20 Glibenclamide Glipizide Gliclazide Glimepiride
28 Muller G, et al. Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37

29. Glimepiride Beneficial Effect on Adiponectin Levels
• Glimepiride increases plasma adiponectin levels
whilst achieving control of glycemia
Evolution of adiponectin and HbA1c levels during 12 weeks of
Glimepiride treatment
11 9
concentration (µg/mL)
10
10.2
Plasma adiponectin
9 8
HbA1c (%)
A study in 17 elderly
patients with type 2
8 diabetes who were
8.2 treated with Glimepiride
for 12 weeks.
7 7
7.5
6.6 6.9
6 6.5
5 6
Baseline 4 weeks 8 weeks 12 weeks
Plasma adiponectin HbA1c (%)
29 Tsunekawa T, et al. Diabetes Care 2003; 26(2); 285-289

30. GLIMEPIRIDE IS MORE THAN AN
INSULIN SECRETAGUGE !!!

31. Glimepiride : Efficacy Proven in Monotherapy
Tight glycemic control (HbA1c<7.2%) Glimepride : decreased FPG by 46
was achieved in 69% of Glimepiride patients mg/dL more and 2-hour PPG by 72 mg/dL
and 32% of placebo patients more than placebo (p<0.001)
Change from baseline to week 22 Change from baseline to week 22 in
in median HbA1c median FPG and 2-hour PPG
Prospective,
Baseline HbA1c randomized, double-
blind, placebo- FPG PPG
9.1% 8.9% controlled, dose-
0 titration study. T2DM n=117 n=118 n=108 n=101
Δ in glucose concentration (mg/dL)
0
-1% patients received
Glimepiride (n=123) or
Δ in median HbA1c (%)
-1 placebo (n=126) for a -20 -13
-2.4%# 10-week dose-titration
period and then the -40 -31
-2 optimal dose (1 to 8
7.9% mg) for 12 weeks. -60
54% of patients on -59*
-3 active treatment -80
received <4 mg/day
Glimepiride
-4 6.7% -100
HbA1c at Endpoint -120
-117*
*p<0.001 vs placebo -140
Glimepiride Placebo
Schade DS et al. J Clin Pharmacol 1998;38:636-51
31

32. Adding sulfonylurea to metformin is particularly
effective in lowering HbA1c
Drug 1 more beneficial Drug 1 less beneficial
Drug 1
Glyb vs. other SU
TZD vs. SU
TZD vs. Met
Repag vs. SU
SU vs. Met
SU vs. Acarbose
Met + TZD vs. Met
SU + TZD vs. SU
Met + SU vs. Met
Met + SU vs. SU
Glyb: glyburide -1.5 -1.0 -0.5 0 0.5
TZD: thiazolidinedione
Repag: repaglinide Weighted mean difference in
SU: sulfonylurea HbA1c Value, %
Met: metformin 32
Bolen S, et al. Ann Intern Med 2007;147:386-399.

33. Glimepiride + Metformin Combination vs Monotherapy
Superior glycemic control with metformin + Glimepiride
Evolution in FBG over time according to treatment
225
209 mg/dl
Metformin
Mean FBG (mg/dL)
200 Prospective,
Glimepiride 207 mg/dl multicenter,
randomized, double-
blind, double-dummy
175 parallel group study of
372 T2DM patients
Metformin + Glimepiride inadequately controlled
by metformin 850 mg
150 tid. Patients received
158 mg/dl metformin, Glimepiride
or both for 20 weeks.
125
0 3 6 9 12 15 18 20
Titration Maintenance
Treatment Duration (wk)
Glimepiride Metformin Metformin + G;imepiride
33 Charpentier G et al. Diabet Med. 2001;18:828-34

34. Efficacy: Glimepiride + Metformin Combination vs
Pioglitazone + Metformin
Glimepiride + metformin provides faster glycemic control
than pioglitazone + metformin
Change in HbA1c over time
Glimepiride + Metformin (n = 96) Pioglitazone + Metformin (n = 107)
9
Open-label,
8.5 randomized, forced-
Mean HbA1C (%)
titration study in 203
8 * adults with poorly
controlled T2D (HbA1c
7.5 * 7.5-10%)on metformin
monotherapy.
* Glimepirideor
7 pioglitazone, titrated
to maximum doses,
6.5 was added to
metformin therapy
and patients were
6 followed for 26
0 6 12 20 26 weeks.
Time (Weeks)
*p<0.05 vs metformin + pioglitazone
Adapted from Umpierrez G, et al. Curr Med Res Opin 2006; 22(4): 751-759

35. Efficacy: Glimepiride + Gliptin Combination
• Combining sitagliptin with Glimepiride improves glycemic control1
Difference in LSM change from baseline in HbA1c relative
to placebo
Baseline HbA1c
8.4% 8.3% Randomized,
0 placebo-controlled
-0.1 study in 441 patients
with T2D poorly
-0.2 controlled by
Glimepiride + sitagliptin Glimepiride or
-0.3
∆ in HbA1c (%)
glimepiride +
-0.4 Glimepiride + metformin (HbA1c
-0.5 -0.57* metformin + sitagliptin ≥7.5% and ≤10.5%). In
addition to their
-0.6 usual therapy,
-0.7 patients received
-0.89* sitagliptin 100mg or
-0.8
placebo for 24
-0.9 weeks.
-1
*p<0.001 vs placebo Hermansen K, et al. Diabetes Obes Metab 2007; 9: 733-745
1
The EU’s Committee for Medicinal Products for Humans (CHMP) recently recommended that
sitagliptin be approved for use in combination with a sulfonylurea and for triple therapy in
combination with metformin + sulfonylurea2
2
European Medicines Agency, 15 Nov 2007: Available at
http://emea.europa.eu/pdfs/human/opinion/Januvia_53120907en.pdf

36. Efficacy: Glimepiride + Insulin Analog Combination
• Superior glycemic control with insulin glargine + Glimepiride +
metformin vs 70/30 insulin as initial therapy
Adjusted mean decrease in HbA1c at week 24 according to
treatment
All patients (n=371) Elderly patients (n=130)
24-week, multinational
Baseline HbA1c 8.85 8.83 8.8 8.9 open, parallel group
0 Insulin clinical study. Insulin-
-0.2 glargine naïve T2DM subjects
(n=371) with poor
-0.4 + glycemic control on OAD
∆ in HbA1c (%)
Glimepiride (sulfonylurea +
-0.6 metformin) were
+ metformin
-0.8 randomized to once-daily
morning insulin glargine
-1 + Glimepiride and
-1.2 -1.31 70/30 insulin metformin (glargine +
-1.4 OAD) or to 30% regular/
-1.4 70% human NPH insulin
-1.64* (70/30) twice daily
-1.6 7.49 without OADs
7.4
-1.8 -1.9†
-2 7.15
HbA1c at endpoint 7.0 *p=0.0003; †p=0.003 vs 70/30 insulin
36 Janka HU et al. Diabetes Care. 2005; 28: 254-259; Janka HU, et al. J Am Geriatr Soc 2007; 55: 182-188

37. SAFETY ?!!!

38. Safety: Hypoglycemia vs Glibenclamide
Significantly lower incidence of severe hypoglycemic events
with Glimepiride vs glibenclamide (0.86 vs 5.6/1000 person-years)
Incidence of severe* hypoglycemic events
according to treatment
6
# Episodes/1000 person-years
Prospective, population-
based, 4-year study to
6.5x compare frequency of
4 severe hypoglycemia in
less patients with T2DM
risk of 5.6 treated with
Glimepiride (estimated
hypo n=1768)
versus glibenclamide
2 (estimated n=1721)
0.86
0
Glimepiride Glibenclamide
*Defined as requiring IV glucose or glucagon
Holstein A et al. Diabetes Met Res Rev 2001; 17:467-73

39. Safety: Weight
• Reduction in glycemia with Glimepiride is accompanied by significant and
stable weight loss
Mean intra-individual changes from baseline in body weight
and HbA1c
Months of treatment
4 12 18
0 Open, uncontrolled,
Change from baseline
observational study.
1770 T2DM patients
-1 -1.4* were enrolled and 284
-1.5* were followed-up for 1.5
-1.7* years. Patients
-1.9* received 0.5 to > 4 mg
-2 Glimepiride once daily.
Baseline HbA1c: 8.4%;
-2.9† -3.0‡ body weight: 79.8kg
-3
Body weight (kg) HbA1c (%)
*p<0.0001; †p<0.05; ‡p<0.005 vs baseline
Weitgasser R et al. Diabetes Res Clin Pract 2003; 61: 13-19

40. Safety: Weight
• The higher the BMI, the greater the weight loss
Change in body weight after 2 months of treatment with
Glimepiride according to baseline BMI
BMI at baseline
0.5 <20 ≥19 to <25 ≥25 - <30 ≥30
0.2
0
Weight loss (kg)
-0.4
-0.5
-1.0
-1.4
-1.5
-2.0 -2.2
-2.5
Scholz GH, et al. Clin Drug Invest 2001; 21: 597-604

41. CARDIAC SAFETY ?!!!

42. University Group Diabetes Program
• Study Design
Randomized Clinical Trial
1000 Patients with Type 2 Diabetes
Assigned to Diet, Insulin or Sulphonylureas
Primary Outcomes – Cardiovascular Events

43. University Group Diabetes Program
Study Terminated
Increased Risk of Cardiovascular Mortality
p < 0.05

47. Glimepiride Beneficial Effect on Cardiovascular Risk Factors
Glimepiride significantly reduces cardiovascular risk markers
Reductions metabolic parameters after 12 months of
treatment with Glimepiride
Lp(a) PAI-1 Hcy
mg/dL (ng/mL) (µmol/L)
0
Randomized, double-
-5
Change from baseline
blind study in which
patients with type 2
-10
diabetes were treated
-15 -21.4† with Glimepiride
(n=62)or repaglinide
-20 ng/mL (n=62) for 12 months.
-25
-30
-35 -39.7* -40.1*
mg/dL µmol/L
-40
-45
Lp(a) = Lipoprotein A
PAI-1 = plasminogen activator inhibitor-1
*p<0.01; †p<0.05 vs baseline Hcy = homocysteine
De Rosa, et al. Clin Ther 2003; 25(2); 472-484

48. Cardiovascular Safety: Ischemic Preconditioning
Unlike glibenclamide, Glimepiride does not block the beneficial
cardioprotective effect of ischemic preconditioning
Mean ST segment depression during
balloon occlusion according to treatment
p = 0.049 p = 0.01 p = NS
100
% change in mean ST shift
Double-blind,
randomized,
placebo-controlled
trial in 45 patients
with stable coronary
artery disease. Mean
50 ST segment shift (mV)
after repetitive
balloon dilatation
was measured to
compare the effects
of Glimepiride
glibenclamide and
0 placebo on ischemic
Placebo Glimepiride(n=15) Glibenclamide preconditioning.
(n=15) (n=15)
Baseline After drug administration
Klepzig et al. Eur Heart J 1999;20:439-446

49. Cardiovascular Safety: Ischemic Preconditioning
• Glimepiride maintains KATP channel-dependent peripheral
vasodilation, unlike glibenclamide
Mean (SEM) % change in forearm blood flow in response to
intra-arterial infusion with 2.25 mg/min/dL diazoxide
*p value compared with placebo
900
% change in forearm blood flow
*p = NS The effects on forearm
blood flow of co-
700 administration of
diazoxide +
Glimepiride or
*p < 0.01 glibenclamide were
500 assessed in healthy
males volunteers
(n = 12 per group).
300
100
Placebo Glimepiride Placebo Glibenclamide
n=12 2.5 µg/min/dL n=12 0.33 µg/min/dL
(n=12) (n=12)
Bijlstra PJ et al. Diabetologia. 1996;39:1083-1090

50. Cardiovascular Safety: Ischemic Preconditioning
Glimepiride maintains and glibenclamide blunts the
anti-anginal effect of ischemic preconditioning
Mean (SD) chest pain scores during angioplasty
Non-diabetic
Diabetic group
group Myocardial responses
were assessed
Glib + Glimepiri following coronary
Control Glib Glimepiri Glib Glimepiri
Nic de + Nic angioplasty in
(n=7) (n=6) de (n=7) (n=6) de (n=5)
(n=6) (n= 6) diabetic and non-
diabetic subjects
Inflation 1 5.9 5.2 6.2 5.8 6.2 3.2 4.4 receiving Glimepiride
(2 mg or usual dose)
± 0.9 ± 1.5 ± 0.8 ± 0.8 ± 0.8 ± 0.8† ± 1.5 or glibenclamide (10
mg or usual dose).
Inflation 2 2.4 5.3 3.2 5.5 3.4 2.7 4.0
± 0.5* ± 1.5 ± 0.8* ± 1.5 ± 0.9* ± 0.8† ± 1.2
*p<0.05 v. inflation 1 within same group. † p<0.05 vs Glib group alone at same time.
Glib = glibenclamide; Nic = nicorandil.
Lee TM, Chou TF. J Clin Endocrinol Metab. 2003;88:531-537

51. Safety: All-Cause Mortality
In combination with metformin, Glimepiride is associated with lower all-cause
mortality than other sulfonylureas with less selectivity for β-cell receptors
Kaplan-Meier survival analysis
1.0
Glimepiride or gliclazide
Retrospective,
observational cohort
Repaglinide study in T2D
0.9 outpatients. A total of
Cumulative survival
696 patients received
insulin secretagogues
in combination with
0.8 biguanides. A Kaplan-
Glibenclamide Meier survival analysis
was conducted in
patients treated with
Yearly mortality metformin in
0.7 Glimepiride 0.4% combination with
Gliclazide 2.1%* glibenclamide,
gliclazide, repaglinide
Repaglinide 3.1%*
or Glimepiride .
Glibenclamide 8.7%**
0.6
Time
* P < 0.05 vs Glimepiride 0 10.0 20.0 30.0 40.0 (months)
**P <0.01 vs all comparators
Monami M, et al. Diabetes Metab Res Rev 2006; 22(6): 477-482

53. GLIMEPIRIDE IN 2010
A NON-STOPPING WEALTH OF EVIDENCE

54. 2010
2010
Xu dan-yan et al. diabetes research and clinical practice 88(2010 ) 71–75

55. Research Design and methods
2010
• Objective:
– To investigate the effects of Glimepiride on blood glucose
in patients with newly diagnosed type 2 diabetes mellitus
(T2DM) in connection with plasma lipoproteins and
plasminogen activity.
• Methods
– A total of 565 T2DM patients received Glimepiride (n =
333) or Glibenclamide (n = 232) for 12 weeks. The level of
blood glucose (BG), glycated hemoglobin (HbA1C), the
insulin resistance (IR) state, plasma lipoproteins, tissue-
type plasminogen activator (t-PA) and plasminogen
activator inhibitor type I (PAI-1) were observed before
and after a 12 weeks of treatment.
Xu dan-yan et al. diabetes research and clinical practice 88(2010 ) 71–75

56. Results Cont. 2010
Conclusion: Glimepiride can rapidly and
stably improve glycemic control and
lipoprotein metabolism, significantly
alleviate insulin resistance and enhance
fibrinolytic activity.
Xu dan-yan et al. diabetes research and clinical practice 88(2010 ) 71–75

57. 2010
2010
Pantalone K. M. et al. DIABETES CARE(33)-6, 2010, 1224 - 29

58. Research Design and methods
2010
• Objective: The purpose of this study is to assess the
relationship of individual sulfonylureas and the risk of overall
mortality in a large cohort of patients with type 2 diabetes.
• Methods: A retrospective cohort study , 11,141 patients
with type 2 diabetes (4,279 initiators of monotherapy with
glyburide, 4,325 initiators of monotherapy with glipizide,
and 2,537 initiators of monotherapy with glimepiride), ≥ 18
years of age, with and without a history of coronary artery
disease (CAD), and not on insulin or a non-insulin injectable
at baseline. The patients were followed for mortality
Pantalone K. M. et al. DIABETES CARE(33)-6, 2010, 1224 - 29

59. Results 2010
• No statistically significant difference in the risk of
overall mortality was observed among these agents
in the entire cohort,
But
• evidence of a trend towards an increased overall
mortality risk with glyburide vs. glimepiride (HR
1.36; CI 0.96-1.91) and glipizide vs. glimepiride (HR
1.39; 95% CI 0.99-1.96), in those with documented
CAD was found.
Pantalone K. M. et al. DIABETES CARE(33)-6, 2010, 1224 - 29

60. Mortality Risk with Sulfonylurea Monotherapy
2010
Conclusion: The results did not identify an
increased mortality risk among the
individual sulfonylureas but did suggest that
glimepiride may be the preferred
sulfonylurea in those with underlying CAD.
Pantalone K. M. et al. DIABETES CARE(33)-6, 2010, 1224 - 29

61. Conclusion
Glimepiride the 3rd generation SU:
– Unique dual mode of action
– Fast and sustained blood glucose lowering effect
– Ideal for combination with insulin and/or other oral
antidiabetic agents
– Benefits beyond blood glucose-lowering
– Clinically proven safety profile
– Glimepiride and Metformine in fixed dose combination
presentation offer a synergistic combination serving the efficacy
and safety objectives needed in the management of T2DM and
Described in ADA/EASD Guidelines.
61