Talk given on the launch of Onglyza at Kollam to a physician group.

1. Saxagliptin in clinical practice
Mathew John, MD, DM, DNB
Endocrinologist
Providence Endocrine & Diabetes Specialty Centre
www.endocrinologydiabetes.com

2. Agenda
• Diabetes mellitus: current scenario
• Unmet medical needs : why we need newer therapies ?
• Drugs acting on incretin axis
• Saxagliptin: overview
efficacy trials
safety trials
• Rational positioning
• Cardiovascular safety

3. World diabetes map 2025
http://www.oxan.com/worldnextweek/2007-11-08/Diabetesmedicaltimebomb.aspx

4. State of current glycemic control:
NHANES
Hoerger TJ . Is Glycemic Control Improving in U.S. Adults? Diabetes Care January 2008 vol. 31 no. 1 81-86

5. Nearly Half to 2/3rd of All Adult Patients With T2DM
Remain Uncontrolled on Their Current Therapy
Parameter DiabCare Asia1 DEDICOM2
Year of study 1998 2005
Total patients 2269 819
Mean age (yrs) 53 54
Mean HbA1c 8.9 NA
% having HbA1c <7% 50 38
% tested for HbA1c 7.8 13
1. Raheja BS et al. JAPI 2001;49:717-22; 2.Nagpal J et al. Diabetes Care 2006; 29:2341-8

6. UKPDS results of Intensive therapy
Risk reduction vs. conventional therapy

7. Unmet needs in diabetes therapeutics
• Progressive nature of disease: beta cell failure, need to
frequently modify therapy
• Hypoglycemia risk: with sulphonylureas, insulin,
combinations
• Weight gain: sulphonylureas, insulin, pioglitazone
• Cardiovascular disease

8. Normal Glucose Homeostasis: Role of
Incretins1,2
In response to meals, incretin Fat Increased
1 hormones (GIP and GLP-1)
are increasingly released from Glucose
the small intestine Uptake
Insulin Secretion
DPP-4
Enzymes
GI Tract β Indirect Glucose
Incretin Effect Pancreas suppression
Homeostasis
α of glucagon
Glucagon Secretion
Pancreatic cells
Incretins (GIP/GLP-1)
2 respond to high
levels of incretins
β Pancreatic beta cell
Liver
DPP-4 enzymes Decreased
α Pancreatic alpha cell
3 break down
incretins
Glucose
Production
GIP=glucose-dependent insulinotropic peptide; GLP-1=glucagon-like peptide-1; DPP-4=dipeptidyl peptidase-4.
1. Kim W et al. Pharmacol Rev. 2008;60:470-512.
2. Drucker DJ. Cell Metab. 2006;3:153-165.

9. T2DM: Role of Incretins1,2
In adults with T2DM, Fat Impaired
1 incretins are released,
but the incretin-mediated Glucose
effects are diminished Uptake
DPP-4 Insulin Secretion
Enzymes
GI Tract β Less indirect
Diminished suppression Hyperglycemia
Pancreas
Incretin Effect α of glucagon
Glucagon Secretion
Incretin action on
Incretins (GIP/GLP-1) 2 pancreatic cells is
reduced
β Pancreatic beta cell
Liver
α Pancreatic alpha cell Increased
Glucose
Production
1. Kim W et al. Pharmacol Rev. 2008;60:470-512.
2. Drucker DJ. Cell Metab. 2006;3:153-165.

10. Saxagliptin
DPP 4 inhibitor
Potent, selective, reversible inhibitor
10 fold more potent that Sitagliptin and Vildagliptin
Active metabolite : M2: 2 fold less potent

11. Relative Selectivity of Saxagliptin
Selectivity for DPP-4 vs DPP-8/9*
Saxagliptin
DPP-4 selectivity
Saxagliptin Active Metabolite
Versus DPP-8 ~400 fold ~950
Versus DPP-9 ~75 fold ~160
* Calculated using Ki; the inhibitor concentration needed for 50% inhibition of the target enzyme; substrate-independent.
DPP=dipeptidyl peptidase.
Kirby MS et al. Poster presented at: 3rd International Conference on Dipeptidyl Peptidases and Related Proteins; April 23-25, 2008;
Antwerp, Belgium.

12. Clinical Pharmacology:
Pharmacokinetics
Absorption
• Median time to max. concentration (Tmax) following 5 mg
once daily dose was 2 hrs for saxagliptin & 4 hrs for its
active metabolite
• Saxagliptin may be administered with or without food
Distribution
• In vitro protein binding of saxagliptin and its active
metabolite in human serum is negligible
• Changes in blood protein levels in various disease states
(eg, renal or hepatic impairment) are not expected to
alter the disposition of saxagliptin

13. Clinical Pharmacology:
Pharmacokinetics
Metabolism
• Metabolism of saxagliptin is primarily mediated by cytochrome
P450 3A4/5 (CYP3A4/5)
• Major metabolite of saxagliptin is also a DPP-4 inhibitor- one-half as
potent as saxagliptin
Excretion
• Saxagliptin is eliminated by both renal & hepatic pathways
• Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75%
of the dose was excreted in the urine as saxagliptin, its active
metabolite, and total radioactivity, respectively
• Following a single oral dose of Saxagliptin 5 mg to healthy subjects,
mean plasma terminal half-life (t1/2) for
– saxagliptin was 2.5 hrs
– active metabolite 3.1 hs respectively

14. Saxagliptin
Studies

15. Saxagliptin Has Been Proven in Well-
Controlled Clinical Trials
• All Phase 3 trials were multicenter, multinational, randomized, double-
blind controlled studies
• The primary efficacy endpoint for all studies was A1C change from
baseline at 6 months
Phase 3 (6)
N=4148
Monotherapy(2) Initial Combo Add-On Combination
Trials With MET (3)
(N=766) (N=1306) Therapy Trials
Entry A1C: 7.0%–10.0% Entry A1C: 8.0%–12.0% (N=2076)
MET=metformin; SU=sulfonylurea; TZD=thiazolidinedione.

16. Saxagliptin Has Been Proven in Well-
Controlled Clinical Trials
Add-On Combination
Therapy Trials
(N=2076)
Add-On to the SU
Add-On to MET Add-On to a TZD
(N=743)
Glibenclamide (N=565)
Entry A1C: 7.0%–10.0% (N=768) Entry A1C: 7.0%–10.5%
Entry A1C: 7.5%–10.0%

17. Saxagliptin add on to
Metformin
24 week data

18. In addition to diet and exercise
Saxagliptin 5 mg Added to MET Provided Extra Help for
Adult Patients Uncontrolled on MET Plus Placebo:
A1C Results
Percentage of Patients Achieving
Change in A1C at 6 Months*
A1C <7% at 6 Months
Saxagliptin 5 mg + MET Placebo + MET 100.0
Percentage of Patients (%)
(n=186) (n=175)
Mean Change From Baseline (%)
Mean baseline: 8.1 % Mean baseline: 8.1 %
0.2 80.0
0.0 60.0
+0.1% 44%
-0.2
40.0
-0.4
20.0
17%
-0.6
0.0
-0.8 Saxagliptin 5 mg + MET Placebo + MET
–0.7% (n=186) (n=175)
Mean baseline: 8.1 % Mean baseline: 8.1 %
-1.0
P<0.0001 vs placebo + MET P<0.05 vs placebo + MET
*Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
DeFronzo RA The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately
Controlled Type 2 Diabetes With Metformin Alone Diabetes Care 32:1649–1655, 2009

19. Saxagliptin 5 mg Added to MET Provided Significant
Reductions in A1C at 6 Months
0.4
Mean Change From Baseline* (%)
0.2
Placebo + MET
0.0
-0.2
-0.4
-0.6
-0.8 Saxa 5 mg + MET
-1.0
BL 4 6 8 12 16 20 24 24
LOCF
Weeks
*Includes patients with a baseline and week 24 value.
Week 24 (LOCF) includes intent-to-treat population using last observation on study prior to pioglitazone rescue therapy for
patients needing rescue. Mean change from baseline is adjusted for baseline value.

20. In addition to diet and exercise
Saxagliptin 5 mg Added to MET Provided Statistically
Significant Reductions in FPG and PPG
Change in FPG at 6 Months* Change in 2-Hour PPG†
at 6 Months*
Saxagliptin 5 mg + MET Placebo + MET Saxagliptin 5 mg + MET Placebo + MET
(n=187) (n=176) (n=155) (n=135)
Mean baseline: 179 mg/dL Mean baseline: 175 mg/dL Mean baseline: 296 mg/dL Mean baseline: 295 mg/dL
Mean Change From Baseline (mg/dL)
Mean Change From Baseline (mg/dL)
10 10
0 0
+1 mg/dL
-10 -10
-20 -20
–22 mg/dL –18 mg/dL
-30 -30
-40 -40
-50 –23 mg/dL -50
Greater Reduction When
-60 Saxagliptin 5 mg Added -60
–58 mg/dL P<0.05 vs placebo + MET
-70 -70
P<0.05 vs placebo + MET
*Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
†As part of a 3-hour oral glucose tolerance test (OGTT).
DeFronzo RA The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately
Controlled Type 2 Diabetes With Metformin Alone Diabetes Care 32:1649–1655, 2009

21. Saxagliptin add on to
Metformin
102 week data

22. HbA1c Mean Change From Baseline (LOCF) at
Week 102
SAXA 5mg + MET PBO + MET
Baseline HbA1c: 8.0 - 8.1%
0.4
Diabetes duration: 6.3 - 6.7 years
0.2
HbA1c (%) Mean ∆ From BL±SE
BL
0.0
-0.2
-0.4
-0.6
BL 4 8 12 20 30 37 50 63 76 89 102
Weeks
Ravichandran S, et al. Diabetologia 2009; 52(Suppl. 1):S60 [Abstract] & Oral Presentation at EASD 2009

23. HbA1c Mean Change From Baseline (LOCF) at
Week 102
SAXA 5mg + MET PBO + MET
FPG 120-min PPG HbA1c <7%
SAXA (mg) SAXA (mg) SAXA (mg)
Dose 5+MET PBO+MET Dose 5+MET PBO+MET Dose 5+MET PBO+MET
n observed= 31 15 n observed= 46 24 n observed= 13 15
BL mean 179 175
12.0 10 50
9.0
-min
Percentage of patients Achieving
0.0
6.0 40 30
Adjusted Mean Change in 120-
Adjusted Mean Change in
HbA1c <7% (95% CI)
FPG (mg/dL) SE
PPG (mg/dL) SE
3.0 3.0
±
±
±
± ± -4 30
0.0
-20
-3.0
20 12
-6.0 -30
-9.0
10
-40
-12.0 -35
-15.0 -11 -50 0
SAXA: Saxagliptin; MET: Metformin; PBO: Placebo
Ravichandran S, et al. Diabetologia 2009; 52(Suppl. 1):S60 [Abstract] & Oral Presentation at EASD 2009

24. Patients on Glibenclamide
Saxagliptin add on
vs.
Glibenclamide uptitration

25. In addition to diet and exercise
Saxagliptin 5 mg Added to a Submaximal Dose of GLIB
Saxagliptin as Add-On Combination Therapy With GLY
768 adult patients with T2DM with inadequate glycemic control
Number of Patients
on a submaximal dose of the SU glibenclamide alone
A1C Entry Criteria ≥7.5%–≤10%
Duration 24 weeks
Base Therapy Submaximal dose of Glib for 2 months or greater
Single-blind, 4-week, diet and exercise lead-in period, and placed
Lead-in Therapy
on GlIB 7.5 mg once daily
4 arms: Saxagliptin (2.5 or 5 mg) + 7.5 mg GLIB,
Treatment Arms*
PBO + 10 mg GLIB
Rescue Protocol MET rescue, added on to existing study medication
*Patients who received placebo were eligible to have Glib up-titrated to a total daily dose of 15 mg. Up-titration of GLIB was not permitted in patients who
received Saxagliptin 2.5 mg or 5 mg. Dose titration of Saxagliptin was not permitted during the study.

26. Saxagliptin: Add on to Sulphonylurea
Add Saxagliptin 5 mg
768 adult patients
On 7.5 mg of
Glibenclamide
Uptitrate Glibenclamide
to 15 mg/day
Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R. Saxagliptin Added to a Submaximal-Dose of
Sulphonylurea Improves Glycaemic Control Compared With Uptitration of Sulphonylurea in Patients With Type 2 Diabetes: A
Randomized Controlled Trial. Int J Clin Pract. 2009:63:1395-1406.

27. In addition to diet and exercise
Saxagliptin 5 mg Added to a Submaximal
Dose of GLIB: A1C Results
Change in A1C at 6 Months* Percentage of Patients Achieving
A1C <7% at 6 Months
Saxagliptin 5 mg + Placebo + Up-Titrated 100.0
GLIB 7.5 mg (n=250) GLIB (n=264) P<0.05 vs placebo
Mean baseline: 8.4% + up-titrated GLIB
Percentage of Patients (%)
Mean baseline: 8.5%
0.2
Mean Change From Baseline (%)
80.0
0.0
+0.1% 60.0
-0.2
40.0
-0.4
23%
-0.6 20.0
–0.6% P<0.0001 vs placebo 9%
+ up-titrated GLY
-0.8
0.0
Saxagliptin 5 mg + Placebo + Up-Titrated
-1.0 92% of patients in the GLIB 7.5 mg (n=250) GLIB (n=264)
placebo + SU group required up- Mean baseline: 8.5% Mean baseline: 8.4%
titration to the maximum SU
study dose of 15 mg
*Intent-to-treat population using last observation on study prior to MET rescue therapy.
Chacra AR . Int J Clin Pract. 2009:63:1395-1406

28. Saxagliptin 5 mg Added to a Submaximal
Dose of GLIB: FPG and PPG Results
Change in FPG at 6 Months* Change in 2-Hour PPG†
at 6 Months*
Saxagliptin 5 mg + Placebo + Up-Titrated Saxagliptin 5 mg + Placebo + Up-Titrated
GLIB 7.5 mg (n=252) GLIB (n=265) GLIB 7.5 mg (n=202) GLIB (n=206)
Mean baseline: 175 mg/dL Mean baseline: 174 mg/dL Mean baseline: 315 mg/dL Mean baseline: 323 mg/dL
Mean Change From Baseline (mg/dL)
Mean Change From Baseline (mg/dL)
10 10
0 0
+1 mg/dL +8 mg/dL
-10 -10
–10 mg/dL
-20 -20
-30 –10 mg/dL -30
Improvement When
-40 Onglyza 5 mg Added -40 –34 mg/dL
-50 -50
P<0.05 vs placebo P<0.05 vs placebo
+ up-titrated GLIB + up-titrated GLIB
-60 -60
-70 -70
*Intent-to-treat population using last observation on study prior to MET rescue therapy.
†As part of a 3-hour OGTT.
Chacra AR . Int J Clin Pract. 2009:63:1395-1406

29. Saxagliptin Plus GLIB: Incidence of
Hypoglycemia
Incidence (%) of Hypoglycemia
Add-on to the SU Glibenclamide study
Saxagliptin 5 mg + Saxagliptin 2.5 mg + Placebo +
GLIB 7.5 mg GLIB 7.5 mg Up-Titrated GLIB
Reported
14.6% 13.3% 10.1%
Hypoglycemia*
Confirmed
0.8% 2.4% 0.7%
Hypoglycemia†
There was no significant differences between different groups in
the reported and confirmed hypoglycemia
*Adverse reactions of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required.
†Definedas symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤50 mg/dL.

30. Patients on Thiazolidinedione
Saxagliptin add on Vs. Placebo

31. In addition to diet and exercise
Saxagliptin 5 mg Provided Extra Help for Patients Struggling to
Gain Glycemic Control on a TZD
Saxagliptin as Add-On Combination Therapy With a TZD
565 adult patients with T2DM with inadequate glycemic control on
Number of Patients
TZD alone
A1C Entry Criteria ≥7%–≤10.5%
Duration 24 weeks
Pioglitazone (30-45 mg once daily) or rosiglitazone (4 mg once
Base Therapy daily or 8 mg either once daily or in two divided doses of 4 mg) for
at least 12 weeks
Single-blind, 2-week, diet and exercise placebo lead-in period,
Lead-In Therapy during which patients received TZD at their pre-study dose for the
duration of the study
Treatment Arms* 3 arms: Saxagliptin (2.5 or 5 mg) + TZD, PBO + TZD
Rescue Protocol MET added on to existing study medications
*Dose titration of Onglyza or TZD was not permitted during the study.

32. Saxagliptin 5 mg Provided Statistically
Significant A1C Reductions When Added to
a TZD
Percentage of Patients Achieving
Change in A1C at 6 Months* A1C <7% at 6 Months
Saxagliptin 5 mg + TZD Placebo + TZD 100.0
Percentage of Patients (%)
(n=183) (n=180)
Mean Change From Baseline (%)
Mean baseline: 8.4% Mean baseline: 8.2%
0.2 80.0
0.0 60.0
-0.2
42%
40.0
-0.4 –0.3% 26%
20.0
-0.6
-0.8 0.0
Saxagliptin 5 mg + TZD Placebo + TZD
P<0.0001 vs placebo + TZD (n=184) (n=180)
-1.0 –0.9% Mean baseline: 8.4% Mean baseline: 8.2%
P<0.05 vs placebo + TZD
*Intent-to-treat population using last observation on study prior to MET rescue therapy.

33. Saxgliptin 5 mg Added to a TZD Provided
Statistically Significant Reductions in FPG
and PPG
Change in FPG at 6 Months* Change in 2-Hour PPG†
at 6 Months*
Saxagliptin 5 mg + TZD Placebo + TZD Saxagliptin 5 mg + TZD Placebo + TZD
(n=185) (n=181) (n=134) (n=127)
Mean baseline: 160 mg/dL Mean baseline: 162 mg/dL Mean baseline: 303 mg/dL Mean baseline: 291 mg/dL
10 10
0 0
Mean Change From
–3 mg/dL
Mean Change From
Baseline (mg/dL)
Baseline (mg/dL)
-10 -10
-20 -20
–17 mg/dL –15 mg/dL
-30 -30
-40 –15 mg/dL -40
Greater Reduction When -50
-50 Onglyza 5 mg Added
-60
-60 P<0.05 vs placebo + TZD
P<0.05 vs placebo + TZD -70
-70 –65 mg/dL
*Intent-to-treat population using last observation on study prior to MET rescue therapy.
†As part of a 3-hour OGTT.

34. Saxagliptin
Safety & Tolerability

35. 35Version 1.3
Saxagliptin: Incidence of Adverse Events
Overall Incidence of Adverse Events Was Similar to Placebo
Pooled Analysis of Adverse Reactions
Occurring in ≥5% of Patients and More
Commonly Than Placebo
In Monotherapy and Add-On Therapy Studies*
Saxagliptin 5 mg Placebo
(N=882) (N=799)
Upper respiratory
7.7% 7.6%
tract infection
Urinary tract
6.8% 6.1%
infection
Headache 6.5% 5.9%
*Prespecified pooled analysis of 2 monotherapy studies, the add-on to MET study, the add-on to the SU glibenclamide study,
and the add-on to a TZD study; 24-week data regardless of glycemic rescue.

36. 36Version 1.3
Saxagliptin: Discontinuation of Therapy
Due to Adverse Events
• Discontinuation of therapy due to adverse events occurred in 3.3% and 1.8%
of patients receiving Saxagliptin and placebo, respectively
Most Common Adverse Events Associated
With Discontinuation of Therapy*
Percent of Patients
Saxagliptin Saxagliptin
Comparator
5 mg 2.5 mg (N=799)
(N=882) (N=882)
Lymphopenia 0.5% 0.1% 0.0%
Rash 0.3% 0.2% 0.3%
Blood creatinine increase 0.0% 0.3% 0.0%
Blood creatine phosphokinase
0.2% 0.1% 0.0%
increase
• There was a dose-related mean decrease in absolute lymphocyte count observed
with Saxagliptin
*Reported in at least 2 patients treated with Saxagliptin

37. 37Version 1.3
Saxagliptin: Incidence of Hypoglycemia
Incidence of Reported Hypoglycemia
Across Phase 3 Clinical Trials
Percent of Patients
Saxagliptin Saxagliptin
Comparator
5 mg 2.5 mg
Add-On to MET 5.8% 7.8% 5.0%
Initial Combo With MET 3.4% — 4.0%
Add-On to the SU Glyburide 14.6% 13.3% 10.1%
Add-On to a TZD 2.7% 4.1% 3.8%
Pooled Monotherapy 5.6% 4.0% 4.1%

38. Cardiovascular safety
Cardiovascular safety :
MACE (Major Adverse CV Events)
Ongoing CV trials : SAVOR-TIMI 53

39. Multiple Analytical Methods for
Relative Risk1
• 41 of CV death/MI/ stroke
(MACE), 40 CEC*-adjudicated
CV events, and 61 Sponsor
identified acute cardiovascular
events assessed by multiple
analytic methods showed similar
results for relative risk
• Onglyza was not associated
with an increased risk of CV
events in a pooled retrospective
analysis of the Phase 2/3 clinical
program
* Clinical Events Committee
1Frederich
R et al 2010 A systematic assessment of cardiovascular outcomes in the saxagliptin drug
development program for type 2 diabetes. Post graduate Medicine 122 (3)

40. Incidence Rate Ratios1
• For investigator identified CV
death, MI or stroke, the results
within individual studies were
consistent with the pooled
analysis
• Onglyza was not associated with
an increased risk of CV events in a
pooled retrospective analysis of
the Phase 2/3/ clinical program
1FrederichR et al 2010 A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program for type 2
diabetes. Post graduate Medicine 122 (3)

41. Kaplan Meier Analysis1
• This Kaplan Meier analysis of
MACE and all cause mortality
does not suggest increased
risk for CV death, MI or stroke
either early or late after
initiation of saxagliptin
treatment.
1Frederich R et al 2010 A systematic assessment of cardiovascular outcomes in the saxagliptin drug development program
for type 2 diabetes. Post graduate Medicine 122 (3)

42. Cardiovascular risk factors (in addition to T2D)
Saxagliptin controlled Phase 2b/3 pooled population
Data on file. Not in public domain

43. Ongoing CV trials of Saxagliptin
• Saxagliptin Assessment of Vascular Outcomes Recorded
in Patients with Diabetes Mellitus" trial (SAVOR-TIMI 53)
• Multicenter, randomized, double-blind, placebo-controlled
Phase 4 study, to evaluate treatment with Saxagliptin, a
dipeptidyl peptidase-4 (DPP4) inhibitor, in adult type 2
diabetes patients with cardiovascular risk factors.
• The five-year study will follow approximately 12,000
patients with type 2 diabetes

44. Saxagliptin
Hepatic Impairment
Renal Impairment

45. 45Version 1.3
Saxagliptin: Renal Impairment
• Mild Impairment, creatinine clearance [CrCl] ≤50
mL/min: No dosage adjustment
• Moderate or severe renal impairment, or with end-stage
renal disease (ESRD) requiring hemodialysis (creatinine
clearance [CrCl] ≤50 mL/min). Saxagliptin 2.5 mg is
recommended.
• Saxagliptin should be administered following hemodialysis.
Saxagliptin has not been studied in patients undergoing peritoneal
dialysis.
• Assessment of renal function is recommended prior to initiation of
Saxagliptin and periodically thereafter.

46. 46Version 1.3
Saxagliptin: Hepatic Impairment
• In subjects with hepatic impairment (Child-Pugh classes
A, B, and C)
• Mean Cmax and AUC of saxagliptin were up to 8% and 77%
higher, respectively, compared to healthy matched controls
following administration of a single 10 mg dose of
saxagliptin.
• The corresponding Cmax and AUC of the active metabolite
were up to 59% and 33% lower, respectively, compared to
healthy matched controls.
• These differences are not considered to be clinically
meaningful.
• No dosage adjustment is recommended for patients with
hepatic impairment

47. Saxagliptin
Dosing

48. Convenient Once-Daily Dosing
Dosing Considerations for Saxagliptin • Standard dose : 5
Recommended Dose mg/day
Recommended dose once
or
5 mg once daily 2.5 mg once daily daily taken regardless of
meals
• Taken any time
Moderate-to-severe renal
impairment,
2.5 mg once daily or ESRD requiring of day, with or
hemodialysis
(CrCl ≤50 mL/min)
without food
Tablets Not Actual Size.
Co-administration with
strong CYP3A4/5
inhibitors*
• 24-hour glycemic
control
*Such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone,
nelfinavir, ritonavir, saquinavir, and telithromycin. ESRD= end-stage renal disease

49. FDA approval
Saxagliptin is approved for
Monotherapy in patients not controlled on diet / exercise
Add on therapy to Metformin, SU or Thiazolidinedione

50. AACE 2010 guidelines
HbA1c : 6.5-7.5 % HbA1c : 7.6-9 % HbA1c : > 9 %
•Metformin Combination Combination
therapy : 2 agents therapy : 3 agents
•TZD
•Metformin •Metformin
•DPP-4 inhibitors
•TZD •TZD
•Alfa- glucosidase
inhibitors •GLP 1 agonist •GLP 1 agonist
•DPP-4 inhibitors •DPP-4 inhibitors
•Glinides •Glinides
•Sulphonylureas •Sulphonylureas
Rodbard, H., Jellinger, P., et al (2009). Consensus Panel on Type 2 Diabetes Mellitus:
An Algorithm for Glycemic Control. Endocrine Practice, 15(6), 540-559.
•Insulin

51. Algorithm
Tier 1 therapies
Lifestyle + MF Lifestyle + MF
+Basal Insulin +Intensive insulin
At diagnosis
Lifestyle +
Metformin
Lifestyle + MF
+ SU
Step 1 Step2 Step 3
Lifestyle + MF Lifestyle + MF
Tier 2 therapies + Pioglitazone + Pioglitazone++SU
Lifestyle + MF
Lifestyle + MF + Basal Insulin
+ GLP-1 agent
Diabetes Care 32:1–11
Oct 2008 e pub

52. Where to position Saxagliptin
Evidence based
Tier 1 therapies
Lifestyle + MF Lifestyle + MF
+Basal Insulin +Intensive insulin
At diagnosis Saxagliptin
Lifestyle +
Metformin
Saxagliptin
Lifestyle + MF
+ SU /Saxagliptin
Step 1 Step2 Step 3
Lifestyle + MF Lifestyle + MF
Tier 2 therapies + Pioglitazone + Pioglitazone+ SU
Lifestyle + MF
Lifestyle + MF + Basal Insulin/ Saxaglipin
+ Saxagliptin
Diabetes Care 32:1–11
Oct 2008 e pub

53. Key messages
• Saxagliptin is a new potent DPP 4 inhibitor
• It is found to reduce all the key parameters of glycemic
control : FBS, PPBS and HbA1c
• It improves measures of beta cell function
• It is weight neutral
• It has a safety profile similar to placebo

54. Thank you

55. Disclaimer
The material for these slides were derived from various sources
including pictures and cartoons from the world wide web. I have
tried my best to acknowledge all possible sources and references.
However, if I have overlooked any particular reference, it is not
done intentionally. Anyone reproducing materials from this
presentations should acknowledge the author of the original work.
Some of the slides are made by Aztra Zeneca/ Bristol Myers Squibb,
the manufactures of Onglyza. However, all these data are currently
in public domain, paid or otherwise.