ueda2012 unmet needs in diabetes management-d.mgahed

2. Unmet Needs
in Diabetes Management
BY PROFESSOR MEGAHID ABUELMAGD
HEAD OF DIABETES AND ENOCRINE UNIT
MANSOURA EGYPT

3. The Nile

4. The corniche of the
Nile

5. The corniche of the Nile

6. The
corniche
of the
Nile

7. Top 10 countries in number of people with diabetes
(20-79 age group)
International diabetes federation
www.worlddiabetesday.org/files/docs/Top_10_countries.pdf Cited 10-may2011

8. Egypt will face explosive growth of diabetes
0
1,000
2,000
3,000
4,000
5,000
6,000
7,000
8,000
9,000
Egypt
Iran
Iraq
SaudiArabia
Algeria
M
orocco
Syria
Sudan
UAE
Tunisia
Jordan
Kuwait
Lebanon
Libya
Bahrain
2003
2025
Due to a rapidly increasing & ageing
population, Egypt will have the largest
number of people with diabetes in the
region by 2025
Source:DiabetesAtlas,2ndedition,IDF
Diabetes Atlas, 2nd edition, IDF

9. Unmet Needs in Patients with Type 2 DM
A. Achieving Goals
B. Beta Cells Deterioration
C. Complications of Therapy
D. Drugs Available can not Cover All Disease
Aspects ( Limited efficacy )

11. aHbA1c ≤6.5%.
HbA1c=haemoglobin A1c; T2DM=type 2 diabetes mellitus.
Liebl A, et al. Diabetologia. 2002; 45: S23–S28.
In CODE study of a European cohort of over 7000 patients
with T2DM, ONLY 31% of patients had adequate glycemic
control
Patientswithadequateglycaemic
control(%)
Approximately 70% of patients with T2DM do not
reach HbA1c goalsa

12. Percentages of adults reaching targets
(Data from European countries)
Most of patients with T2DM do not achieve HbA1c
goals
25.5
49
0
10
20
30
40
50
60
A1C <6.5%
A1C 6.5-7.6%
%patientsreachingtarget
Alvarez Guisasola F. et al. Diab Metab Obes. 2008. 10 (suppl 1): 8-15
Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study

13. Incidence of microvascular complications
increases with mean HbA1c
HbA1c=haemoglobin A1c.
Incidence rates and 95% confidence intervals for myocardial infarction and microvascular complications by category of mean HbA1c concentration, adjusted for age,
sex and ethnic group, expressed for white men aged 50–54 years at diagnosis and with mean duration of diabetes of 10 years.
Stratton IM. et al. BMJ. 2000; 321: 405–412.
80
60
40
20
0
Adjustedincidence
per1000personyears(%)
5 6 7 8 9 10 11
Mean HbA1c (%)
Myocardial infarction
Microvascular endpoints

14. 0
15
30
45
UKPDS : Significant Risk Reduction for T2DM
Complications with Each 1% Reduction in Mean HbA1c
Risk Reduction with 1% Decline in HbA1c
Micro-
vascular
disease
PVD MI Stroke CHF Cataract
extraction
Death
related to
diabetes
P <0.0001P <0.0001 P=0.035 P=0.021 P <0.0001
37% 43%
14% 12% 16% 19% 21%
CHF=congestive heart failure; HbA1c=hemoglobin A1c; PVD=peripheral vascular disease; MI=myocardial infarction
Adapted from Stratton IM, et al. BMJ. 2000; 321: 405–412.
N=3642

15. UKPDS: Acheiving early glycaemic control may generate a
good legacy effect
HbA1c=haemoglobin A1c.
Diabetes Trials Unit. UKPDS Post Trial Monitoring. UKPDS 80 Slide Set. Available at: http://www.dtu.ox.ac.uk/index.php?maindoc=/ukpds/. Accessed
12 September, 2008; Holman RR, et al. N Engl J Med. 2008; 359: 1577–1589; UKPDS 33. Lancet. 1998; 352: 837–853.
MedianHbA1c(%)
0
6
7
8
9
UKPDS 1998
Conventional
Intensive
Holman et al 2008
Legacy effect
1997
Difference in HbA1c was lost after
first
year but patients in the initial
intensive arm still had lower
incidence of any complication
2007
Patients initially received intensive therapy had a lower
incidence of any complication

16. Reaching the target in late stages of the disease
does not reduce the vascular complications
P=0.14.
Primary outcome: first occurrence of a major cardiovascular event (a composite of myocardial infarction, stroke,
death from cardiovascular causes, congestive heart failure, surgery for vascular disease, inoperable coronary
disease, and amputation for ischaemic gangrene).
Duckworth W, et al. N Engl J Med. 2009; 360: 129–139.
1.0
0.8
0.6
0.4
0.2
0.0
0 2 4 6 8
Probabilityofsurvival
Years
Standard
therapy
Intensive
therapy
892
899
774
770
707
693
No. at risk
Intensive
Standard
639
637
582
570
510
471
252
240
62
55
0
0
VADT
Primary outcome

17. Legacy effect: early glycemic control is the key to
long-term reduction in complications
Achieving glycemic control late in the disease, after a
prolonged period of poor control, does not improve long-
term risk of macrovascular complications2
Long-standing, preceding hyperglycaemia accounted for
the high rate of complications at baseline in VADT3
UKPDS=UK Prospective Diabetes Study; VADT=Veterans Affairs Diabetes Trial.
1Holman RR, et al. N Engl J Med. 2008; 359: 1577–1589.
2Duckworth W, et al. N Engl J Med. 2009; 360: 129–139;
3Del Prato S. Diabetologia. 2009; 52: 1219–1226.
Good legacy effect
Early, strict glycemic control brings benefits,
reducing the long-term risk of microvascular and
macrovascular complications (UKPDS1)

18. Unmet Needs in Patients with Type 2 DM
A. Achieving Goals
B. Beta Cells Deterioration
C. Complications of Therapy
D. Drugs Available can not Cover All Disease
Aspects ( Limited efficacy )

20. Evidence of β-Cell Function Decline Even Before
Diagnosis of T2DM
Adapted from UK Prospective Diabetes Study Group (UKPDS 16). Diabetes. 1995;44:1249-1258.
0
20
40
60
80
100
–12 –10 –8 –6 –4 –2 0 2 4 6
Years Before and After Diagnosis of T2DM
β-CellFunction(%)
Normal
Glucose
Tolerance
Prediabetes
(IFG/IGT)
Progressive loss of β-cell function
occurs before diagnosis
T2DM
Diagnosis

21. Causes of Beta-Cells Dysfunction
Recent studies indicated that pancreatic-cell failure arises from
a combination of :
1.Glucotoxicity
2.lipotoxicity
3.Increased proinflammatory cytokines and leptin
4.Islet cell amyloidal deposition1
5.Insulin secretion
• Response to increased insulin demand B-cell
proliferation
• Response to increased insulin demand Neogenesis
• Response to increased insulin demand apoptosis 2
221-Clinical Therapeutics/Volume 33, Number 5, 2011
2-Rev Endocr Metab Disord (2008) 9:329–343

22. β-cell Function Continues to Decline Regardless of
Intervention in T2DM
T2DM=type 2 diabetes mellitus.
*β-cell function measured by homeostasis model assessment (HOMA).
Adapted from UKPDS Group. Diabetes. 1995; 44: 1249–1258.
0
20
40
60
80
100
–5 –4 –3 –2 –1 0 1 2 3 4 5 6
Years since Diagnosis
β-cellFunction(%)*
Progressive Loss of β-cell Function
Occurs prior to Diagnosis
Metformin (n=159)
Diet (n=110)
Sulfonylurea (n=511)

23. Unmet Needs in Patients with Type 2 DM
A. Achieving Goals
B. Beta Cells Deterioration
C. Complications of Therapy
D. Drugs Available can not Cover All Disease
Aspects ( Limited efficacy )

25. Hypoglycemia is defined as...
• ADA defined hypoglycemia as: “Any abnormally low plasma glucose
concentration that exposes the subject to potential harm”.
Plasma glucose <70 mg/dL (<3.9 mmol/L), with or without symptoms.
• The European Medicines Agency (EMA): Recommended a lower
threshold of plasma glucose (<3 mmol/L) to define hypoglycemia
• Most recent trials defined hypoglycemia as:
(<54 mg /dl - <70 mg/dl)
Clinically severe hypoglycemia as any episode in which a patient is
unable to self-treat
Mild hypoglycemic events, usually defined as self-treated episodes
Minimizing the Risk of Hypoglycemia with Vildagliptin Diabetes Ther (2011) 2(2)

26. Pathophysiology: Hierarchy and thresholds of physiological
mechanisms involved in the response to low blood glucose level
27
This material can only be shown reactively to answer specific questions from physicians.
Arterialisedvenousbloodglucoseconcentration
(mmoI/L)
5.0
0.0
1.0
2.0
3.0
4.0
Cognitive Dysfunction
• Inability to perform
complex tasks
2.8 mmoI/L
Severe
Neuroglycopenia
• Reduced
conscious level
• Convulsions
• Coma
<1.5 mmoI/L
Counter regulatory
hormone release
• Glucagon
• Epinephrine
3.8 mmoI/L
Onset of symptoms
• Autonomic
• Neuroglycopenic
3.2 –
2.8mmoI/L
Neurophysiological Dysfunction
• Evoked responses
3.0 – 2.4mmoI/L
Inhibition of
endogenous insulin
secretion
4.6 mmoI/L
Zammit N, et al. Diabetes care. 2005;28(12):2948–961
82.8 mg/dL
68.4 mg/dL
68.4- 50.4 mg/dL
54- 43.2mg/dL 50.4 mg/dL
<27 mg/dL

27. Treat to Target increases the risk of hypoglycemia
28
1. ACCORD Study Group. N Engl J Med. 2008;358:2545–2559
2. Duckworth W, et al. N Engl J Med. 2009;360:129–139
3. ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560–2572
ACCORD1 VADT2 ADVANCE3
P <0.001
Events(%)
Standard Intensive
16
6
4
2
0
14
12
10
8
18
P <0.01
Standard Intensive
Eventsper100patient-years
6
4
2
0
14
12
10
8
P <0.001
Standard Intensive
Eventsper100patientsperyear
0.6
0.4
0.2
0
0.8
0.7
0.5
0.3
0.1
This material can only be shown reactively to answer specific questions from physicians.

28. Consequences of hypoglycaemia (1)
Hypoglycaemia
Cardiovascular
complications3
Weight gain
by defensive eating5
Coma3
Increased risk
of car accident6
Hospitalisation
costs4
Loss of
consciousness3
Increased risk
of seizures3
Death2,3
Increased risk
of dementia1
1Whitmer RA, et al. JAMA. 2009; 301: 1565–1572; 2Bonds DE, et al. Br Med J. 2010; 340: b4909;
3Barnett AH. Curr Med Res Opin. 2010; 26: 1333–1342; 4Jönsson L, et al. Value Health. 2006; 9: 193–198;
5Foley JE, Jordan J. Vasc Health Risk Manag. 2010; 6: 541–548; 6Begg IS, et al. Can J Diabetes. 2003; 27: 128–140; 7McEwan P, et al. Diabetes Obes
Metab. 2010; 12: 431–436.
.
Reduced
quality of life7

29. aDiet initially then sulfonylureas, insulin and / or metformin if FPG >15 mmol/L.
CI=confidence interval; FPG=fasting plasma glucose.
n=number of patients at baseline.
1UKPDS 34. Lancet. 1998; 352: 854–865;
2Kahn SE, et al. N Engl J Med. 2006; 355: 2427–2443.
UKPDS: up to 8 kg in 12 years1
ADOPT: up to 4.8 kg in 5 years2
0
88
92
96
100
0 1 2 3 4 5
0
0 1 6 9 12
1
2
3
4
5
6
7
8
Years from randomisation
Years
Annualised slope (95% CI)
Weight(kg)
Treatment difference (95% CI)
Rosiglitazone vs metformin 6.9 (6.3 to 7.4); P <0.001
Rosiglitazone vs glyburide 2.5 (2.0 to 3.1); P <0.001
Changeinweight(kg)
Insulin (n=409)
Glibenclamide (n=277)
Metformin (n=342)
Conventional treatment
(n=411)a
Rosiglitazone, 0.7 (0.6 to 0.8)
Glyburide, -0.2 (-0.3 to 0.0)
Metformin, -0.3 (-0.4 to -0.2)
Most therapies result in weight gain over time

30. The consequences of hypoglycaemia (2)
Hypoglycaemia
Cardiovascular
complications3
Weight gain
by defensive eating5
Coma3
Increased risk
of car accident6
Hospitalisation
costs4
Loss of
consciousness3
Increased risk
of seizures3
Death2,3
Increased risk
of dementia1
1Whitmer RA, et al. JAMA. 2009; 301: 1565–1572; 2Bonds DE, et al. Br Med J. 2010; 340: b4909;
3Barnett AH. Curr Med Res Opin. 2010; 26: 1333–1342; 4Jönsson L, et al. Value Health. 2006; 9: 193–198;
5Foley JE, Jordan J. Vasc Health Risk Manag. 2010; 6: 541–548; 6Begg IS, et al. Can J Diabetes. 2003; 27: 128–140;
7McEwan P, et al. Diabetes Obes Metab. 2010; 12: 431–436.
.
Reduced
quality of life7

31. Hypoglycemic events may
trigger inflammation by
inducing the release of C-
reactive protein (CRP), IL-
6, and vascular endothelial
growth factor (VEGF)
Underlying endothelial
dysfunction leading to
decreased vasodilatation
may also contribute to
cardiovascular risk.
32
This material can only be shown reactively to answer specific questions from physicians.
Desouza CV, et al. Diabetes Care. 2010; 33:1389–394
Cardiovascular Complications with Hypoglycemia

32. *P=0.01; **P=0.02; ***P <0.01.
CL=confidence limit; HDL-C=high-density lipoprotein cholesterol.
Abraira C. Oral Presentation. Presented at the 68th Scientific Sessions of the American Diabetes Association; 6–10 June 2008, San Francisco, USA.
HR (Lower CL, Upper CL)
Risk of death
Lower Higher
Hypoglycemia
HbA1c
HDL-C
Age
Prior event
4.042 (1.449, 11.276)*
1.213 (1.038, 1.417)**
0.699 (0.536, 0.910)*
2.090 (1.518, 2.877)***
3.116 (1.744, 5.567)***
Hypoglycemia was a Strong Predictor of CV
Deaths in VADT study
0 2 4 6 8 10 12
Hazard Ratio

33. 34
©2008 New England Journal of Medicine. Used with permission
Gerstein HC, et al, for the Action to Control Cardiovascular Risk in Diabetes Study Group.
N Engl J Med 2008;358:2545-2559.
Intensive Glycemic Control and Cardiovascular
Outcomes: ACCORD Study
Primary Outcome: Nonfatal MI, Nonfatal Stroke, CVD
death

34. Intensive
n (%)
Standard
n (%)
HR
(95% CI) P value
Primary 352 (6.86) 371 (7.23)
0.90
(0.78-1.04)
0.16
Secondary
Mortality 257 (5.01) 203 (3.96)
1.22
(1.01-1.46)
0.04
Nonfatal MI 186 (3.63) 235 (4.59)
0.76
(0.62-0.92)
0.004
Nonfatal Stroke 67 (1.31) 61 (1.19)
1.06
(0.75-1.50)
0.74
CVD Death 135 (2.63) 94 (1.83)
1.35
(1.04-1.76)
0.02
CHF 152 (2.96) 124 (2.42)
1.18
(0.93-1.49)
0.17
ACCORD: increased mortality rate in the intensive arm
compared with the standard arm
CHF=congestive heart failure; CI=confidence interval; CVD=cardiovascular disease; HR=hazard ratio; MI=myocardial infarction.
Gerstein HC. Oral Presentation. Presented at: 68th Scientific Sessions of the American Diabetes Association;
June 6-10, 2008; San Francisco, CA; Action to Control Cardiovascular Risk in Diabetes Study Group. N Engl J Med. 2008;358:2545-2559.

35. Consequences of hypoglycaemia (3)
Hypoglycaemia
Cardiovascular
complications3
Weight gain
by defensive eating5
Coma3
Increased risk
of car accident6
Hospitalisation
costs4
Loss of
consciousness3
Increased risk
of seizures3
Death2,3
Increased risk
of dementia1
1Whitmer RA, et al. JAMA. 2009; 301: 1565–1572; 2Bonds DE, et al. Br Med J. 2010; 340: b4909;
3Barnett AH. Curr Med Res Opin. 2010; 26: 1333–1342; 4Jönsson L, et al. Value Health. 2006; 9: 193–198;
5Foley JE, Jordan J. Vasc Health Risk Manag. 2010; 6: 541–548; 6Begg IS, et al. Can J Diabetes. 2003; 27: 128–140;
7McEwan P, et al. Diabetes Obes Metab. 2010; 12: 431–436.
.
Reduced
quality of life7

36. ADA Recommendations include...
Prevention of hypoglycemia is
critical in treatment strategy for
Type 2 DM
37
Phung et al. Effect of Noninsulin Antidiabetic Drugs Added to Metformin Therapy on Glycemic Control, Weight Gain, and Hypoglycemia in Type 2 Diabetes. JAMA. 2010;303(14):1410-1418

37. CVD=cardiovascular; HbA1c=haemoglobin A1c; T2DM=type 2 diabetes mellitus.
American Diabetes Association. Diabetes Care. 2011; 34 (Suppl 1): S4–S10.
Normal Controlled T2DM Uncontrolled T2DM
≥7%6.1–6.9%HbA1c <6%
Initiate or change
treatment whenever
HbA1c levels are ≥7%
• Initiate or change therapy when HbA1c
≥7% without hypoglycaemia
• Less stringent HbA1c goals may be
appropriate for patients with a history of
hypoglycaemia and CVD
ADA Recommendations include...

38. HbA1c=haemoglobin A1c; OAD, oral antidiabetic drugs.
Jacob AN, et al. Diabetes Obes Metab. 2007; 9:386–393;
Kahn SE, et al. N Engl J Med. 2006; 355: 2427–2443;
Wright AD, et al. J Diabetes Complications. 2006; 20: 395–401
* Abraira C. Oral Presentation. Presented at: 68th Scientific Sessions of the American Diabetes Association; June 6-10, 2008; San Francisco, CA.
Duckworth W, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009; 360: 129–139..
Decreasing HbA1c is associated with increased risks
of hypoglycaemia, weight gain and CV death*
Weight gain
and
hypoglycaemia
Bodyweight
HbA1c
Plasmaglucose

39. Unmet Needs in Patients with Type 2 DM
A. Achieving Goals
B. Beta Cells Deterioration
C. Complications of Therapy
D. Drugs Available can not Cover All Disease
Aspects ( Limited efficacy )

40. Factors to Consider when Choosing an
Anti-hyperglycemic Agent
• Effectiveness in lowering glucose
• Glycemic control that may reduce long-term
complications
• Patient profile
• Safety profile
• Tolerability
• Expense
41
Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

41. Pancreatic Islet Dysfunction Leads to Hyperglycemia
in T2DM
↑ Glucose
Fewer
-cells
-cells
Hypertrophy
Insufficient
Insulin
Excessive
Glucagon
–+
↓ Glucose
Uptake
↑ HGO
+
HGO=hepatic glucose output.
Adapted from Ohneda A, et al. J Clin Endocrinol Metab. 1978; 46: 504–510; Gomis R, et al. Diabetes Res Clin Pract. 1989; 6: 191–198.

42. Pharmacologic targets of current drugs used in
the treatment of T2DM
-glucosidase inhibitors
Delay intestinal carbohydrate
absorption
Thiazolidinediones
Decrease lipolysis in
adipose tissue,
increase glucose
uptake in skeletal
muscle and decrease
glucose production in
liverSulfonylureas
Increase insulin secretion
from pancreatic -cells
DDP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; T2DM=type 2 diabetes mellitus.
Adapted from Cheng AY, Fantus IG. CMAJ. 2005; 172: 213–226. Ahrén B, Foley JE. Int J Clin Pract. 2008; 62: 8–14.
Glinides
Increase insulin secretion
from pancreatic -cells

43. Current Oral Therapies do not Address Islet Cell
Dysfunction
Pancreatic Islet Dysfunction
Inadequate
glucagon
suppression
(-cell
dysfunction)
Progressive
decline of β-cell
function
Insufficient
Insulin secretion
(β-cell
dysfunction)
Sulfonylureas
Glinides
TZDs
Metformin
TZDs
Ins. Resistance
(Impaired insulin action)
TZD= Thiazolidinedione; T2DM= Type 2 Diabetes Mellitus
Adapted from DeFronzo RA. Br J Diabetes Vasc Dis. 2003;3(suppl 1):S24–S40

44. Metformin
TZDs
α-Glucosidase
inhibitors
*Role uncertain
Adapted from Inzucchi SE. JAMA. 2002;287:360-372. Kolterman OG, et al. Am J Health-Syst Pharm 2005;62:173-181; DeFronzo RA, et al.
Diabetes Care 2005;28:1092-1100.
Weight gain, edema, CHF
GI effects (flatulence, diarrhea)
GI effects (nausea, diarrhea), lactic acidosis (rare)
SUs
Meglitinides
Hypoglycemia, weight gain, hyperinsulinemia*
Major Adverse Events of Current Treatments
for T2DM Limit the Efficacy

45. Risk of hypoglycemia with different
Sulfonylureas
*<50 mg/dL.
Tayek J. Diabetes Obes Metab. 2008; 10: 1128–1130.
0
5
10
15
20
25
30
Glipizide
8.70
Tolbutamide
3.50
Chlorpropamide
16.00
Glyburide
16.00
Severe hypoglycaemia*
n/1000 person years =
RelativeRisk(%)
Gliclazide
0.85
Glimepiride
0.86
4.6*
8.0*
11.5*
12.3* 12.3*
24.0*

46. RECORD study results: secondary endpoints –
cardiovascular
All cause
Heart failure*
Hazard Ratio (95% CI)
0.86 (0.68, 1.08); P=0.19
0.84 (0.59, 1.18); P=0.32
0.72 (0.49, 1.06); P=0.10
0.93 (0.74, 1.15); P=0.50
2.10 (1.35, 3.27); P=0.001
MI
Stroke
CV death,
MI or stroke
*Fatal and non-fatal.
CI=confidence interval; CV=cardiovascular; MI=myocardial infarction.
Home PD et al. Lancet. 2009; 373: 2125–2135.
Rosiglitazone
(n=2220)
Control
(n=2227)
46
64
154
63
2961
165
56 1.14 (0.80, 1.63); P=0.47
Hazard ratio (95% CI)
0.5 1.0 2.0 3.0 4.0
Death
CV
136
60
157
71

47. Use of TZDs is Associated with Increased
Incidence Heart Failure
0 6 12 18 24 30 36
0
1
2
3
6
5
7
8
9
10
4
TZD 8.8%†
No TZD 5.5%
Subjects at Risk
TZD 5,441 2,474 1,203 580 266 108 26 0
No TZD 28,103 13,373 6,836 3,638 1,414 330 89 0
Months
Delea TE et al. Diabetes Care 2003; 26: 2983-2989, (a retrospective study using a healthcare insurance claims database)
Subjects%*
*Adjusted estimates of the percentage of subjects with diagnosis of heart failure, † p<0.001
P<0.001

48. PROactive: incidence of edema and magnitude of
weight gain with Pioglitazone
21.6
13.0
0
5
10
15
20
25 3.6
-0.4
-1
0
1
2
3
4
% of Edema without HF Weight Gain (kg)
Placebo
Pioglitazone <45 mg daily
HF=heart failure.
Adapted from Dormandy JA, et al. Lancet. 2005; 366: 1279–1289.
P <0.0001

49. Pharmacologic targets GLP-1 based therapy
used in the treatment of T2DM
GLP-1 analogs
Improve pancreatic islet glucose
sensing, slow gastric emptying,
improve satiety
DDP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1; T2DM=type 2 diabetes mellitus.
Adapted from Cheng AY, Fantus IG. CMAJ. 2005; 172: 213–226. Ahrén B, Foley JE. Int J Clin Pract. 2008; 62: 8–14.
DPP-4 inhibitors
Prolong GLP-1 action leading to
improved pancreatic islet glucose
sensing, increase glucose uptake

50. Current Oral Therapies do not Address Islet Cell
Dysfunction
Pancreatic Islet Dysfunction
Inadequate
glucagon
suppression
(-cell
dysfunction)
Progressive
decline of β-cell
function
Insufficient
Insulin secretion
(β-cell
dysfunction)
Sulfonylureas
Glinides
TZDs
Metformin
TZDs
VildagliptinVildagliptin
Ins. Resistance
(Impaired insulin action)
TZD= Thiazolidinedione; T2DM= Type 2 Diabetes Mellitus
Adapted from DeFronzo RA. Br J Diabetes Vasc Dis. 2003;3(suppl 1):S24–S40

51. A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dl (7.0 mmol/l)
(Fasting: i.e. No calories intake for at least 8 hours)
OR
Two-hour plasma glucose ≥200 mg/dl (11.1
mmol/l) during an OGTT
OR
A random plasma glucose ≥200 mg/dl (11.1
mmol/l)
Criteria for the Diagnosis of Diabetes
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

52. 2010 ADA Type 2 Diabetes Treatment Algorithm
• Regarding Diabetes Mellitus Diagnostic Criteria :

53. ADA 2011 Glycemic Goals
DIABETES CARE, VOLUME 34, SUPPLEMENT 1, JANUARY 2011

54. Categories of increased risk for diabetes
(Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG
or
2-h plasma glucose in the 75-g OGTT
140-199 mg/dl (7.8-11.0 mmol/l): IGT
or
A1C 5.7-6.4%
Prediabetes: IFG, IGT, Increased A1C
*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately
greater at higher ends of the range.
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.

55. Vildagliptin:
in T2DM Management

57. Inhibition of DPP-4 increases active GLP-1
DPP-4 DPP-4
inhibitor
Meal
Intestinal
GLP-1
release
Active
GLP-1
Active
GLP-1
DPP-4
GLP-1
inactive
(>80% of pool)
GLP-1
inactive
No DPP-4
inhibitor present
DPP-4
inhibitor present
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon-like peptide-1.
Adapted from Rothenberg P, et al. Diabetes. 2000; 49 (Suppl 1): A39. Abstract 160-OR.
Adapted from Deacon CF, et al. Diabetes. 1995; 44: 1126–1131.

58. DPP4 Inhibitors
• A different mechanism for overcoming the loss of
incretin activity in patients with diabetes involves
inhibition of the DPP-4 enzyme ( DPP4 Inhibitors )
thus prolonging the activity of endogenous GLP-1
• These agents are all orally administered and rapidly
absorbed, as 100% inhibition of enzyme activity can
be observed within 30 minutes after administration of
vildagliptin

59. Vildagliptin Comprehensive Clinical Development
Program
OAD mono
OAD combo Insulin combo
Insulin mono
Prediabetes
Diet and
exercise
Mono vs placebo
TZD add-on
Insulin add-on
Metformin add-on vs placebo
SU add-on
Mono head to head
vs metformin
Overall and in elderly
Mono head to head
vs rosiglitazone
Initial combo
with TZD
Mono head to head
vs acarbose
Metformin add-on vs TZD
In IFG
In IGT
Metformin add-on vs SU
Initial combo with metformin
IFG=impaired fasting glucose; IGT=impaired glucose tolerance; OAD=oral antidiabetic drug; SU=sulfonylurea; TZD=thiazolidinedione.
Mono head to head
vs SU
Metformin add-on
metformin up-titration

60. Patients Exposure in Vildagliptin Clinical Programa
• Over 22,023 patients overall treated in the clinical program1
>13,856 exposed to vildagliptin
• Over 20,990 patients treated in completed studies2
13,253 exposed to vildagliptin in completed studies
• Patient exposure by treatment duration in completed studies
4034 patients exposed to vildagliptin >1 year
1800 patients exposed to vildagliptin >2 years
aData on file, Novartis Pharmaceuticals. Current as of April 19th, 2010.
1All Phase I-IV studies; numbers do not include EDGE study 2All completed Phase I-IV studies
EDGE study patients number:
Total: 56355 with 64% in vildagliptin arm and 35% in non vildagliptin arm

61. Vildagliptin
as Monotherapy

62. Vildagliptin Dose-Ranging Study: Design and Objective
HbA1c=hemoglobin A1c; T2DM=type 2 diabetes mellitus
Pi-Sunyer FX, et al. Diabetes Res Clin Pract 2007; 76: 132-138.
Drug-naïve
24 weeks2 weeks
N=354
n=88: Vildagliptin 50 mg once daily
n=83: Vildagliptin 50 mg twice daily
n=91: Vildagliptin 100 mg once daily
n=92: Placebo
Design: a 24-week, double-blind, randomized, placebo-controlled,
parallel-group study
Objective: to demonstrate superior HbA1c reduction of vildagliptin
versus placebo
Target population: drug-naïve patients with T2DM; HbA1c 7.5–10%

63. 7.0
7.4
7.8
8.2
8.6
9.0
-4 -2 0 2 4 6 8 10 12 14 16 18 20 22 24
Vilda 50 mg once daily (n=84)
Vilda 50 mg twice daily (n=79)
Vilda 100 mg once daily (n=89)
PBO (n=88)
Vildagliptin Monotherapy: Reductions in HbA1c over
24 Weeks
MeanHbA1c(%)
Time (weeks)
HbA1c=hemoglobin A1c; PBO=placebo; vilda=vildagliptin
Primary intention-to-treat population. *P=0.01; **P <0.001 vs placebo.
Pi-Sunyer F, et al. Diabetes Res Clin Pract 2007; 76: 132-138.
**
**
*

64. Vildagliptin
As
Add-on to
Metformin

65. Vildagliptin add-on to metformin:
Study design and objective
Objective: to demonstrate superior HbA1c reduction with
vildagliptin + metformin vs metformin monotherapy
Target population: T2DM on maximal dose of metformin;
HbA1c 7.5–11%
HbA1c=hemoglobin A1c; T2DM=type 2 diabetes mellitus.
*Patient number refers to primary intention-to-treat population.
Bosi E, et al. Diabetes Care. 2007; 30: 890–895.
n=130: Placebo + metformin
n=143: Vildagliptin 50 mg twice daily + metformin
n=143: Vildagliptin 50 mg once daily + metformin
24 weeks
Metformin
>1500 mg
(monotherapy,
stable dose)
4 weeks
N=416*

66. HbA1c=hemoglobin A1c; met=metformin;
PBO=placebo; vilda=vildagliptin
*P <0.001. Primary intention-to-treat population.
Bosi E, et al. Diabetes Care 2007; 30: 890-895.
Vildagliptin Add-on to Metformin: Reduction in
HbA1c over 24 Weeks
7.2
7.4
7.6
7.8
8.0
8.2
8.4
8.6
−4 0 4 8 12 16 20 24
Time (weeks of treatment)
MeanHbA1c(%)
PBO + met (n=130)
Vilda 50 mg twice daily + met (n=143)
Vilda 50 mg once daily + met (n=143)
Add-on treatment to metformin (2.1 g mean daily)
−0.7% vs PBO
−1.1%vs
PBO
*
*

67. Vildagliptin produces clinically meaningful, dose
related decreases in A1C and
Placebo + metformin (n=130)
Vildagliptin 50 mg twice daily + metformin (n=143)
Vildagliptin 50 mg once daily + metformin (n=143)
FPG=fasting plasma glucose; HbA1c=hemoglobin A1c.
*P <0.001; **P=0.003 vs placebo; ***P <0.001 vs placebo.
Primary intention-to-treat population.
Bosi E, et al. Diabetes Care. 2007; 30: 890–895.
7.2
7.4
7.6
7.8
8.0
8.2
8.4
8.6
−4 0 4 8 12 16 20 24
Time (Weeks)
MeanHbA1c(%)
−0.7% vs placebo
−1.1%
vs placebo
*
*
Time (Weeks)
MeanFPG(mmol/L)
−4 0 4 8 12 16 20 24
8
9
10
11
−0.8 vs placebo
−1.7 vs
placebo
**
***
Add-on Treatment to Metformin (2.1 g Mean Daily)
Duration: 24 weeks vildagliptin add on to metformin
Reduction in HbA1c Reduction in FPG

68. Initial combination
of
Vildagliptin and
Metformin

69. Initial combination of vildagliptin and metformin:
Effective across the hyperglycemia spectrum (data from core
study and open-label sub-study)
~9.9%
96
Change from BL to EP
~8.7%
285
Overall*
>9%
High BL Open-label
Sub-studyb
MeanChangeinHbA1c(%)
≥10%
~10. 6%
35
~9.2%
201
>8%
Subgroups by BL HbA1ca
*P <0.001 vs BL; **100 mg once daily is not a recommended dosing regimen.
Intent-to-treat population. aRaw mean change from baseline;
bLS (least-square) mean change from baseline. BL=baseline; EP=end point;
HbA1c=glycosylated hemoglobin; met=metformin; vilda=vildagliptin.
Bosi E, et al. Diabetes Obes Metab. 2009; 11: 506–515;
a Data on file, Novartis Pharmaceuticals, LMF237A2302 and LMF237A2302S1.
Vilda 100 mg daily** + met 2000 mg
daily open-label sub-study (P <0.001
vs BL)d
High-dose vilda + met (50/1000 mg twice daily)c
BL mean=
n =
>11%
~12. 1%
86
*
As with traditional OADs, vildagliptin as add-on
to metformin substantially reduces HbA1c in
patients with high baseline levels

70. Vildagliptin vs SU
as
Add-on to
Metformin

71. Vildagliptin vs. Glimepiride as add-on to Metformin:
Study design and objective
Study purpose: To demonstrate long-term efficacy and safety of add-on therapy with
vildagliptin vs glimepiride in patients with T2DM inadequately controlled with ongoing
metformin monotherapy
Interim analysis: To demonstrate non-inferiority of vildagliptin vs glimepiride at 1 year
Target population: Patients with T2DM inadequately controlled on stable metformin
monotherapy (metformin minimum dose 1500 mg/day; baseline HbA1c 6.5–8.5%)
n=1393: Glimepiride up to 6 mg once daily + metformin
n=1396: Vildagliptin 50 mg twice daily + metformin
4 weeks
Metformin
HbA1c=haemoglobin A1c; SU=sulfonylurea; T2DM=type 2 diabetes mellitus.* Randomised population.
Ferrannini E et al. Diabetes Obes Metab 2009; 11: 157–166.
1-year interim
analysis
N=2789*
104 weeks

72. In patients uncontrolled with metformin monotherapy
vildagliptin is as effective as Glimepiride over 1 year with
low incidence of hypoglycemia and no weight gain
Glimepiride up to 6 mg once daily + metformin
Vildagliptin 50 mg twice daily + metformin
Number of
hypoglycaemic events
Patients with
1 hypos (%)
Number of severe
hypoglycaemic
events c
Incidence(%)
1389 1383 1389 1383 1389 1383n =
No.ofevents
No.ofevents
16.2
1.7 39
554
Duration: 52 weeks, add-on to metformin: vildagliptin vs glimepiride
Mean HbA1c reduction a Incidence of hypoglycaemia b
BL=baseline; CI=confidence interval
NI=non-inferiority; aPer protocol population ; bSafety population.
cGrade 2 or suspected grade 2 events.
*P <0.001; adjusted mean change from BL to Week 52,
between-treatment difference and P value were from
an ANCOVA model containing terms for treatment,
baseline and pooled centre.
Ferrannini E et al. Diab Obes Metab 2009; 11: 157–166.
MeanHbA1c(%)
0.0
6.5
6.7
6.9
7.1
7.3
7.5
-8 -4 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56
NI: 97.5%
CI (0.02, 0.16)
−0.4%
−0.5%
Time (weeks)
Adjustedmeanchangein
bodyweight(kg)fromBL
(BL mean ~88.8kg)
1117n = 1071
Change in body weight a

73. Vildagliptin vs TZD
as
Add-on to
Metformin

74. Vildagliptin vs Pioglitazone as add-on to metformin:
Study design and objective
Objective: demonstrate efficacy and safety of vildagliptin as add-on to metformin vs
pioglitazone as add-on to metformin over 52 weeks (with interim analysis at 24 weeks)
Target population: patients with T2DM inadequately controlled with metformin monotherapy
(baseline HbA1c 7.5–11%)
Design: randomised, multicentre, active-comparator, 52-week study: 24-week,
double-blind phase (primary objective) followed by a 28-week single-blind phase
N=576*
24 weeks4 weeks 28 weeks
Interim
analysis
Double-blind1 Single-blind2
Metformin
≥1500 mg
HbA1c=haemoglobin A1c; T2DM=type 2 diabetes mellitus.
1Bolli G, et al. Diabetes Obes Metab. 2008; 10: 82–90; 2Bolli G, et al. Diabetes Obes Metab. 2009; 11: 589–595.
n=281: Pioglitazone 30 mg once daily + metformin
n=295: Vildagliptin 50 mg twice daily + metformin

75. BL=baseline; DPP-4=dipeptidyl peptidase-4; HbA1c=haemoglobin A1c.
Per protocol population. *Non-inferiority of vildagliptin to pioglitazone established at both 0.4% and 0.3% margins,
95% confidence interval=(-0.05, 0.26). Adjusted mean change derived from analysis of covariance model.
Bolli G, et al. Diabetes Obes Metab. 2008; 10: 82–90.
Vildagliptin plus metformin:
The only DPP-4 inhibitor with proven efficacy comparable to Pioglitazone plus
metformin at 24 weeks
-1.0
-1.5-1.5
-0.9
-1.8
-1.6
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
Overall
Mean BL ~8.4%
Adjustedmean
changeinHbA1c(%)
HbA1c >9%
Mean BL ~9.7%
n= 264 246
Pioglitazone 30 mg once daily + metformin
Vildagliptin 50 mg twice daily + metformin
73 69
Non-inferior*
Add-on treatment to metformin (2.0 g mean daily)

76. 78
Vildagliptin vs Pioglitazone as add on to Metformin:
No Change in Mean Body Weight
n=277n=293
UnadjustedMean
ChangeinBW(kg)
*
Overall
Mean BL BW ~91 kg
Intention-to-treat population.
BL=baseline; BW=body weight; pio=pioglitazone; vilda=vildagliptin.
*P <0.001 change from baseline.
Bolli G, et al. Diabetes Obes Metab. 2009; 11: 589–595.
Data on file, Novartis Pharmaceuticals, LMF237A2354.
Add-on Treatment to Metformin
Duration : 52 weeks
Pio 30 mg once daily + met
Vilda 50 mg twice daily + met

77. Vildagliptin
and
Beta cell preservation

78. Vildagliptin increases pancreatic Beta cell mass in
neonatal rats
Duttaroy A. et al. European J Pharmacol. 2011; 650: 703–707
Control Vildagliptin
Day 7
BrdU+
cells
Day 7
Apoptag+
cells
Day 21
Insulin+
cells
*p<0.05; **p<0.01
Replication
Apoptosis
-cell Mass

79. ISR/G=insulin-secretory rate relative to glucose concentration
Scherbaum WA, et al. Diabetes Obes Metab. 2008; Epub ahead of print..
Durability of β-cell Function over 2 Years
MeanISR/G(pmol/min/m2/mM)
Time (weeks)
Treatment period Wk 0–52 Treatment period Wk 56–108Washout Washout
Placebo (n=40)
Vildagliptin 50 mg once daily (n=49)
30
−8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112
35
40
45
50
81

80. Safety Profile
of
Vildagliptin

81. 83
In more than 14,000 patients No Increased Risk for
Adjudicated CV Events, Relative to All Comparators*
AEs=adverse events; bid=twice daily; CI=confidence interval; CV=cardiovascular; M-H RR=Mantel-Haenszel risk ratio; qd=once daily; vilda=vildagliptin.
#Vs comparators (all non-vildagliptin treatment groups). All-study safety population.
‡Guidance for Industry: Diabetes Mellitus - Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes, U.S. Department
of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), December 2008.
Schweizer A, et al. DOM 2010 in press.
Vildagliptin Reference M-H RR
n / N (%) n / N (%) (95% CI)
Vilda 50 mg qd# 10 / 1393 (0.72) 14 / 1555 (0.90) 0.88 (0.37–2.11)
Vilda 50 mg bid# 81 / 6116 (1.32) 80 / 4872 (1.64) 0.84 (0.62–1.14)
Risk Ratio
Incidences and Odds Ratios for Adjudicated CV Events by
Treatment
Vildagliptin better Vildagliptin worse
0.1 1 10
#Meta-analysis of vildagliptin 50 mg bid data vs all comparators according to the methodology set by
the US Food and Drug Administration‡ [50 mg bid odds ratio = 0.84 (95% CI 0.62–1.14)].

82. In more than 14,000 patients, Vildagliptin Showed No
increase in liver enzymes Vs comparators
AEs=adverse events; bid=twice daily; CI=confidence interval; qd=once daily;
SAEs=serious adverse events; vilda=vildagliptin. *Vs comparators
(all non-vildagliptin treatment groups). All-study safety (excluding open-label) population.
Vildagliptin better Vildagliptin worse
Vildagliptin Reference Peto odds ratio
n / N (%) n / N (%) (95% CI)
Hepatic AEs
Vilda 50 mg qd* 15 / 1502 (1.00) 14 / 1662 (0.84) 1.29 (0.61–2.70)
Vilda 50 mg bid* 83 / 6116 (1.36) 84 / 4872 (1.72) 0.87 (0.64–1.19)
Hepatic SAEs
Vilda 50 mg qd* 2 / 1502 (0.13) 2 / 1662 (0.12) 1.08 (0.15–7.76)
Vilda 50 mg bid* 6 / 6116 (0.10) 5 / 4872 (0.10) 1.13 (0.35–3.67)
Odds Ratio
0.01 0.1 1 10 100
According to the Prescribing information, vildagliptin should not be used in patients with
hepatic impairment, including patients with pre-treatment alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3x the upper limit of normal
(ULN).
Liver function tests should be performed prior to the initiation of treatment with vildagliptin in order to know the patient’s baseline value. Liver function should
be monitored during treatment with vildagliptin at 3-month intervals during the first year and periodically thereafter.
Ligueros-Saylan M, et al.DOM 2010 in press

83. Vildagliptin All Comparators Peto odds ratio
n / N (%) n / N (%) (95% CI)
Selected Skin-related AEs
•Vilda 50 mg qd 19/1502 (1.26) 11/1662 (0.66) 1.93 (0.93-3.99)
•Vilda 50 mg bid 89/6116 (1.47) 71/4872 (1.46) 1.10 (0.80–1.51)
Selected Skin-related SAEs
•Vilda 50 mg qd 0/1502 (0.00) 1/1662 (0.06) 0.23 (<0.01–7.11)
•Vilda 50 mg bid 6/6116 (0.10) 7/4872 (0.14) 0.84 (0.29–2.49)
0.01 100
Vildagliptin worse
Odds Ratio
Vildagliptin better
0.1 1 10
In more than 14,000 patients ,No increased risk of skin-
related AEs and SAEs with Vildagliptin vs all comparators
Odds ratios for selected skin and vascular- related AEs and SAEs in the all controlled studies (excluding open-label) safety population. (Vilda=
vildagliptin; All comparators= all non-Vilda treatment groups, that is placebo and active comparators. n = number of patients experiencing an AE, N =
total number of patients). Test for heterogeneity of selected skin- and/ or vascular – related AEs: Q = 9.58, p = 0.653 and I2 = 0.00 (vildagliptin 50 mg
qd); Q= 10.79, p= 0.702 and I2 = 0.00 (vildagliptin 50 mg bid). Test for heterogeneity of selected skin- and/ or vascular – related SAEs: Q = 0.20, p =
0.999 and I2 = 0.00 (vildagliptin 50 mg qd); Q= 10.31, p= 0.739and I2 = 0.00 (vildagliptin 50 mg bid).
Ligueros-Saylan M, et al. Diab Obes Metab 2010 ;12:495-509

84. Vildagliptin Monotherapy: Overall AE Profile
Comparable with Placebo (AEs >5%)
Preferred term
Vilda
50 mg
once daily
N=655
n (%)
Vilda
50 mg
twice daily
N=2251
n (%)
Met
<1 mg
twice daily
N=252
n (%)
Rosi
8 mg
once daily
N=267
n (%)
Acar
<100 mg
thrice daily
N=220
n (%)
PBO
N=586
n (%)
Nasopharyngitis 37 (5.6) 128 (5.7) 13 (5.2) 20 (7.5) 14 (6.4) 36 (6.1)
Headache 35 (5.3) 112 (5.0) 13 (5.2) 14 (5.2) 1 (0.5) 23 (3.9)
Dizziness 29 (4.4) 105 (4.7) 10 (4.0) 11 (4.1) 9 (4.1) 20 (3.4)
Upper respiratory
tract infection
11 (1.7) 75 (3.3) 5 (2.0) 8 (3.0) 11 (5.0) 20 (3.4)
Diarrhea 10 (1.5) 64 (2.8) 57 (22.6) 7 (2.6) 6 (2.7) 12 (2.0)
Nausea 10 (1.5) 53 (2.4) 23 (9.1) 2 (0.7) 0 13 (2.2)
Acar=acarbose; AE=adverse event; met=metformin; PBO=placebo; rosi=rosiglitazone; vilda=vildagliptin
Preferred terms are sorted by descending order of incidence in the vildagliptin 50 mg twice-daily group.
A patient with multiple AE occurrences on one treatment is counted once in the AE category for that treatment.
Adapted from Summary of Clinical Safety, 5 December 2007. Tables 4-1g. Novartis Pharmaceuticals.
Pooled analysis at 24 weeks

85. Vildagliptin Monotherapy: Incidence of Hypoglycemic
Events
Patients
Vilda
50 mg
once daily
N=655
n (%)
Vilda
50 mg
twice daily
N=2251
n (%)
Met
<1 mg
twice daily
N=252
n (%)
Rosi
8 mg
once daily
N=267
n (%)
Acar
<100 mg
thrice daily
N=220
n (%)
PBO
N=586
n (%)
With >1 hypoglycemic events 2 (0.3) 7 (0.3) 0 1 (0.4) 0 1 (0.2)
Discontinued for
hypoglycemic events
0 0 0 0 0 0
With grade 2 hypoglycemic
events
0 0 0 0 0 0
Hypoglycemic events are defined as: (a) symptoms patient is able to self-treat and plasma glucose is <3.1 mmol/L (grade 1); (b) symptoms patient is
unable to self-treat, and plasma glucose is <3.1 mmol/L (grade 2).
Acar=acarbose; met=metformin; PBO=placebo; rosi=rosiglitazone; vilda=vildagliptin
Adapted from Summary of Clinical Safety, 5 December 2007. Table 4-1g. Novartis Pharmaceuticals.
Pooled analysis at 24 weeks

86. Vildagliptin: Hypoglycemic Events in Add-on to
Metformin
Hypoglycemic events are defined as: (a) symptoms patient is able to self-treat, and plasma glucose is <3.1 mmol/L (grade 1); (b) symptoms patient is
unable to self-treat, and plasma glucose is <3.1 mmol/L (grade 2); and (c) symptoms patient is unable to self-treat, and no plasma glucose value
available (suspected grade 2).
met=metformin; pio=pioglitazone; vilda=vildagliptin
Data on file, Novartis Pharmaceuticals, CLAF237A2303, 2354.
Vilda
50 mg
once daily
+ met
N=177
n (%)
Vilda
50 mg
twice daily
+ met
N=183
n (%)
Placebo
+ met
N=181
n (%)
Vilda
50 mg
twice daily
+ met
N=295
n (%)
Pio
30 mg
once daily +
met
N=280
n (%)
With >1 hypoglycemic events 1 (0.6) 1 (0.5) 1 (0.6) 1 (0.3) 0
Discontinued due to hypoglycemic
events
0 0 0 0 0
With grade 2 hypoglycemic events 0 0 0 0 0
Patients
Add-on metformin vs placebo
Add-on metformin
vs pioglitazone

88. A1c < 7%
Metformin
failure
Sulfonylureas
TZDs
DPP-4Inhibitor
At a clinical crossroad: Which way you go?
• Efficacy
• Hypoglycemia
• Weight gain
• Effect on b-cell
• CV risk
• Safety & Tolerability

89. Take Home Messages (1/2)
 Early and sustained glycemic control is crucial for prevention
of diabetic complications
 Hypoglycemia is a major barrier for achieving optimal
glycemic control
 DPP-4 inhibitors emerge as a novel approach for
management of type 2 DM

90. Take Home Message (2/2)
• If sustained glycemic control is important
• If avoidance of hypoglycemia is important
• If avoidance of weight gain is important
• If preservation of B-cell function is important
Then………
Vildagliptin is a good option
In management of patients with type 2
DM

91. 93