Glycemic Management in Type 2 Diabetes Efficacy and Safety of Antihyperglycemic Therapies Introduced Since 2004 1

Glycemic Management in Type 2 Diabetes

Efficacy and Safety of Antihyperglycemic Therapies

Introduced Since 2004

1

*P<0.001 vs active comparator monotherapy. †P<0.001 vs active comparator dual therapy.

1. Nauck MA, et al. Diabetes Obes Metab. 2007;9:194-205. 2. Goldstein BJ, et al. Diabetes Care. 2007;30:1979-1987.3. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 4. Vilsbøll T, et al. Diabetes Obes Metab. 2010;12:167-177.

5. Derosa G, et al. Metab Clin Exp. 2010;59:887-895. 6. Dobs AS, et al. J Diabetes. 2013;5:68-79..

A

1C (

%)

Glucose Control With Sitagliptin: Selected Mono and Combination Therapy Studies

-2-1.8-1.6-1.4-1.2

-1-0.8-0.6-0.4-0.2

0

-0.67 -0.66-0.67

-1.13

-0.02

0

-1.4

-0.3

-1.9

-0.67 -0.6

-1.4

-1.1

Monotherapyvs Glipizide52 Weeks1

Initial Combow/ Metformin

24 Weeks2

Add-on to Metformin24 Weeks3

Add-on toInsulin

24 Weeks4

Add-on toPioglitazone vs

Met + Pio12 Months5

Add-on to Rosiglitazone +

Metformin54 Weeks6

N 1172 1091 701 641 151 278

Treatment Sit Glip Sit Met Sit+Met

Met Sit+Met

Ins Sit+Ins

Met +Pio

Sit +Pio

Rosi + Met

Sit +Rosi

+Met

Baseline A1C (%)

7.5 7.5 8.9 8.7 8.8 8.0 8.0 8.6 8.7 8.4 8.5 8.7 8.8

*

* *†

*P<0.001 vs glipizide; †P<0.05 vs sitagliptin.

1. Aschner P, et al. Diabetes Care. 2006;29:2632-2637. 2. Nauck MA, et al. Diabetes Obes Metab. 2007;9:194-205.3. Rosenstock J, et al. Clin Ther. 2006;28:1556-1568. 4. Hermansen K, et al. Diabetes Obes Metab. 2007;9:733-745. 5. Vilsbøll T, et

al. Diabetes Obes Metab. 2010;12:167-177. 6. Derosa G, et al. Metab Clin Exp. 2010;59:887-895.

W

eigh

t (kg

) Weight Changes With Sitagliptin: Selected Mono and Combination Therapy Studies

Monotherapy24 Weeks1


Add-on to Pioglitazone24 Weeks3

Add-on to Glimepiride24 Weeks4

Add-on toInsulin

24 Weeks5

Add-on to Pio vs Met +

Pio12 Months6

N 741 793 353 441 641 151

Treatment PBO Sit Glip Sit Pio Sit +Pio

Glim Sit + Glim

Ins Sit +Ins

Met + Pio

Sit +Pio

†

*

1. Nauck MA, et al. Diabetes Obes Metab. 2007;9:194-205. 2. Goldstein BJ, et al. Diabetes Care. 2007;30:1979-1987.3. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 4. Rosenstock J, et al. Clin Ther. 2006;28:1556-1568.

5 . Hermansen K, et al. Diabetes Obes Metab. 2007;9:733-745. 6. Vilsbøll T, et al. Diabetes Obes Metab. 2010;12:167-177.

Hypoglycemia With Sitagliptin:Selected Studies

0

5

10

15

20

25

30

35

4.9

0.62.8

32

1.1 2.10

7.5 8.0

2.2 1.3 1.1

16.4 16.0

Sitagliptin vs Glipizide

52 weeks1


24 Weeks2


Add-on to Pioglitazone24 Weeks4

Add-on to Glimepiride24 Weeks5

Add-on toInsulin

24 Weeks6

N 793 1091 701 353 441 641

Treatment Sit Glip PBO Met Sit +Met

Met Sit +Met

Pio Sit +Pio

Glim Sit +Glim

Sit +Glim +

Met

Ins Sit +Ins

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

Incidence of Selected Adverse Events With Sitagliptin: Pooled Data

Adverse Event Incidence per 100 patient-years Difference (95% CI)

Sitagliptin 100 mg Nonexposed

Constipation 2.6 1.9 0.8 (0.1, 1.4)

Diarrhea 6.9 9.6 -2.3 (-3.6, -1.0)

Headache 5.8 5.6 0.4 (-0.7, 1.4)

Nasopharyngitis 7.7 7.0 0.9 (-0.3, 2.1)

Pancreatitis 0.08 0.10 -0.02 (-0.20, 0.14)

Rash 1.3 0.9 0.4 (-0.1, 0.8)

Upper respiratory tract infection

8.6 9.0 -0.3 (-1.6, 1.0)

Williams-Herman D, et al. BMC Endocr Disord. 2010;10(7) . http://www.biomedcentral.com/1472-6823/10/7.Engel SS, et al. Int J Clin Pract. 2010;64:984-990.

P<0.0001 vs comparator.

1. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 2. Jadzinsky M, et al. Diabetes Obes Metab. 2009;11:611-622.

3. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 4. Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26:540-549. 5. Chacra AR, et al. Int J Clin Pract. 2009;63:1395-1406. 6. Hollander P, et al. J Clin Endocrinol Metab. 2009;94:4810-4819.

Glucose Control With Saxagliptin:Mono and Combination Therapy



24 Weeks2



Add-on to Glyburide vs Uptitration24 Weeks5

Add-on toTZD

24 Weeks6

N 401 1306 743 801 768 565

Treatment PBO Sax Met Sax +Met

Met Sax +Met

Sit +Met

Sax +Met

Gly Sax +Gly

TZD Sax +TZD

Baseline A1C (%) 7.9 8.0 9.4 9.4 8.1 8.1 7.7 7.7 8.4 8.5 8.2 8.4

*

A

1C (

%)

*

*

**

*P=0.01 vs glyburide uptitration.

1. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 2. Jadzinsky M, et al. Diabetes Obes Metab. 2009;11:611-622.3. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 4. Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26:540-549.5. Chacra AR, et al. Int J Clin Pract. 2009;63:1395-1406. 6. Hollander P, et al. J Clin Endocrinol Metab. 2009;94:4810-4819.

Wei

ght (

kg)

Weight Changes With Saxagliptin: Mono and Combination Therapy



24 Weeks2




Add-on toTZD

24 Weeks6

N 401 1306 743 801 768 565


Met Sax +Met

Sit +Met

Sax +Met

Gly Sax +Gly

TZD Sax +TZD

*

1. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 2. Jadzinsky M, et al. Diabetes Obes Metab. 2009;11:611-622.3. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 4. Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26:540-549.5. Chacra AR, et al. Int J Clin Pract. 2009;63:1395-1406. 6. Hollander P, et al. J Clin Endocrinol Metab. 2009;94:4810-4819.

Hypoglycemia With Saxagliptin:Mono and Combination TherapyMonotherapy

24 Weeks1


24 Weeks2




Add-on toTZD

24 Weeks6

N 401 1306 743 801 768 565


Met Sax +Met

Sit +Met

Sax +Met

Gly Sax +Gly

TZD Sax +TZD

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

Incidence of Adverse Events With Saxagliptin

Adverse Events* Patients (%)

Saxagliptin 5 mg Placebo

Headache 6.5 5.9

Upper respiratory tract infection

7.7 7.6

Urinary tract infection 6.8 6.1

*Occurring in ≥5% of patients receiving saxagliptin 5 mg and more commonly than in placebo-treated patients.

Onglyza (saxagliptin) prescribing information. Princeton, NJ: Bristol-Meyers Squibb. 2011.

* P<0.0001 vs comparator. † P<0.0001 vs placebo and vs metformin 1000 mg twice daily.

HD, high-dose metformin (1000 mg twice daily); LD, low-dose metformin (500 mg twice daily).

1. Del Prato S, et al. Diabetes Obes Metab. 2011;13:258-267. 2. Haak T, et al. Diabetes Obes Metab. 2012;14:565-574. 3. Gomis R, et al. Diabetes Obes Metab. 2011;13:653-661. 4. Taskinen MR, et al. Diabetes Obes Metab. 2011;13:65-74.

5. Gallwitz B, et al. Lancet. 2012;380:475-483. 6. Owens DR, et al. Diabet Med. 2011;28:1352-61.

Glucose Control With Linagliptin:Mono and Combination Therapy


Initial Combo w/ Metformin

24 Weeks2

Initial Combow/ Pioglitazone

24 Weeks3


Add-on to Metformin2 Years5

Add-on to Metformin +

SU24 Weeks6

N 503 791 389 700 1552 1055

Treatment PBO Lin Lin Met HD

Lin + Met LD

Lin + Met HD

Pio Lin +Pio

Met Lin +Met

Glim + Met

Lin + Met

Met + SU

Lin +Met +

SU

Baseline A1C (%)

8.0 8.0 8.7 8.5 8.7 8.7 8.6 8.6 8.0 8.1 7.7 7.7 8.1 8.2

A

1C (

%)

*

**

*

†

Weight Changes With LinagliptinInitial Combo w/

Metformin24 Weeks1


24 Weeks2

Add-on toMetformin24 Weeks3

Add-on toMetformin2 Years4

N 791 389 700 1552

Treatment Lin Met HD

Lin + Met LD

Lin + Met HD

Pio Lin +Pio

Met Lin +Met

Glim + Met

Lin + Met

W

eigh

t (kg

)

* P<0.0001 vs comparator.


1. Haak T, et al. Diabetes Obes Metab. 2012;14:565-574. 2. Gomis R, et al. Diabetes Obes Metab. 2011;13:653-661.3. Taskinen MR, et al. Diabetes Obes Metab. 2011;13:65-74. 4. Gallwitz B, et al. Lancet. 2012;380:475-483.

*

Hypoglycemia With Linagliptin:Mono and Combination Therapy

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

0

5

10

15

20

25

30

35

40

0.63.4

02.8

36

14.8

0.33.5

1.2 0.6

7

22.7

0 0


Initial Combo w/ Metformin

24 Weeks2


24 Weeks3


Add-on to Metformin2 Years5

Add-on to Metformin +

SU24 Weeks6

N 503 791 389 700 1552 1055

Treatment PBO Lin Lin Met HD

Lin + Met LD

Lin + Met HD

Pio Lin +Pio

Met Lin +Met

Glim + Met

Lin + Met

Met + SU

Lin +Met +

SU


1. Del Prato S, et al. Diabetes Obes Metab. 2011;13:258-267. 2. Haak T, et al. Diabetes Obes Metab. 2012;14:565-574. 3. Gomis R, et al. Diabetes Obes Metab. 2011;13:653-661. 4. Taskinen MR, et al. Diabetes Obes Metab. 2011;13:65-74.

5. Gallwitz B, et al. Lancet. 2012;380:475-483. 6. Owens DR, et al. Diabet Med. 2011;28:1352-61.

Incidence of Adverse Events With Linagliptin

Tradjenta (linagliptin) prescribing information. Ridgefield, CT: Boehringer Ingelheim, Inc.; 2012.


Linagliptin 5 mg(n=3625)

Placebo(n=2176)

Nasopharyngitis 7.0 6.1

Diarrhea 3.3 3.0

Cough 2.1 1.4

*Occurring in ≥2% of patients receiving linagliptin 5 mg and more commonly than in placebo-treated patients.

P<0.001 vs comparator(s).

1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Rosenstock J, et al. Diabetes Care. 2010;33:2406–2408.3. Nauck MA, et al. Int J Clin Pract. 2009;63:46-55.4. Pratley RE, et al. Diabetes Obes Metab. 2009;11:167-176.

5. Bosi E, et al. Diabetes Obes Metab. 2011;13:1088-1096. 6. Rosenstock J, et al. Diabetes Obes Metab. 2009;11:1145-1152.

Glucose Control With Alogliptin:Mono and Combination Therapy


Initial Combo w/ Pioglitazone

26 Weeks2


Add-on to Glyburide26 Weeks4

Add-on toMet + Pio52 Weeks5

Add-on to Insulin +/- Met

26 Weeks6

N 329 655 527 500 803 390

Treatment PBO Alo Pio Alo Alo + Pio

Met Alo +Met

Gly Alo + Gly

Met + Pio

Alo + Met + Pio

Ins +/- Met

Alo + Ins +/-

Met

Baseline A1C (%)

7.9 7.9 8.8 8.8 8.8 8.0 7.9 8.1 8.1 8.1 8.3 9.3 9.3

A

1C (

%)

* * * *

*

*

P<0.01 vs comparator.

1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Rosenstock J, et al. Diabetes Care. 2010;33:2406–2408.3. Nauck MA, et al. Int J Clin Pract. 2009;63:46-55.4. Pratley RE, et al. Diabetes Obes Metab. 2009;11:167-176.

5. Bosi E, et al. Diabetes Obes Metab. 2011;13:1088-1096. 6. Rosenstock J, et al. Diabetes Obes Metab. 2009;11:1145-1152.

Weight Change With Alogliptin


Initial Combo w/ Pioglitazone

26 Weeks2





26 Weeks6

N 329 655 527 500 803 390

Treatment PBO Alo Pio Alo Alo + Pio

Met Alo +Met

Gly Alo + Gly

Met + Pio

Alo + Met + Pio

Ins +/- Met

Alo + Ins +/-

Met

W

eigh

t (kg

)

*

1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013. 3. Nauck MA, et al. Int J Clin Pract. 2009;63:46-55.

4. Pratley RE, et al. Diabetes Obes Metab. 2009;11:167-176. 5. Bosi E, et al. Diabetes Obes Metab. 2011;13:1088-1096.6. Rosenstock J, et al. Diabetes Obes Metab. 2009;11:1145-1152.

Hypoglycemia With Alogliptin

Monotherapy26 Weeks1,2





26 Weeks6

N 329 527 500 803 390

Treatment PBO Alo Met Alo +Met

Gly Alo +Gly

Met +Pio

Alo + Met + Pio

Ins+/- Met

Alo + Ins +/- Met

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

Incidence of Adverse Events With Alogliptin

Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013.


Alogliptin 25 mg(n=5902)

Placebo(n=2926)

Active comparator

(n=2257)

Nasopharyngitis 4.4 3.0 5.0

Headache 4.2 2.5 5.4

Upper respiratory tract infection 4.2 2.1 5.0

*Occurring in ≥4% of patients receiving alogliptin 25 mg and more commonly than in placebo-treated patients.

A

1C (

%)

Glucose Control With Exenatide With/Without Oral Agents

*P<0.001 vs comparator.†All exenatide dosages shown are 10 μg BID.

1. Moretto TJ, et al. Clin Ther. 2008;30:1448-1460 . 2. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 3. Buse JB, et al. Diabetes Care. 2004;27:2628-2635. 4. Zinman B, et al. Ann Intern Med. 2007;146:477-485. 5. Kendall DM et al. Diabetes Care.

2005;28:1083-1091. 6. Heine RJ, et al. Ann Intern Med. 2005;143:559-569.

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

0.4

-0.2

0.1 0.12 0.090.2

-1.1

-0.9-0.8 -0.86 -0.89 -0.9

-1.1



Add-on to Sulfonylurea

30 Weeks3

Add-on to TZD16 Weeks4

Add-on to Metformin + SU

30 Weeks5

Add-on to Met + SU vs Glargine

26 Weeks6

N 233 336 377 233 733 551

Treatment† PBO Exe Met Exe +Met

SU Exe +SU

TZD Exe +TZD

Met +SU

Exe + Met +

SU

Glar + Met +

SU

Exe +Met +

SU

Baseline A1C (%) 8.2 8.2 8.7 8.6 7.9 7.9 8.5 8.5 8.3 8.2

* * ***

W

eigh

t (kg

) Weight Reduction With Exenatide: Mono

and Dual Combination Therapy

*P<0.05 vs comparator. **P<0.0001 vs glargine.†All exenatide dosages shown are 10 μg BID.

1. Moretto TJ, et al. Clin Ther. 2008;30:1448-1460 . 2. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 3. Buse JB, et al. Diabetes Care. 2004;27:2628-2635. 4. Zinman B, et al. Ann Intern Med. 2007;146:477-485. 5. Kendall DM et al. Diabetes Care.

2005;28:1083-1091. 6. Heine RJ, et al. Ann Intern Med. 2005;143:559-569.




30 Weeks3


Add-on to Metformin + SU

30 Weeks5

Add-on to Met + SU vs Glargine

26 Weeks6

N 233 336 377 233 733 551


SU Exe +SU

TZD Exe +TZD

Met +SU

Exe + Met +

SU

Glar + Met +

SU

Exe +Met +

SU

** **

***

*P<0.05 vs placebo.

Moretto TJ, et al. Clin Ther. 2008;30:1448-1460.

S

ysto

lic B

P

(mm

Hg)

Blood Pressure Changes With Exenatide

Monotherapy24 Weeks

N 233

Treatment PBO Exe 10 μg BID

*

†All exenatide dosages shown are 10 μg BID.

1. Moretto TJ, et al. Clin Ther. 2008;30:1448-1460 . 2. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 3. Buse JB, et al. Diabetes Care. 2004;27:2628-2635. 4. Zinman B, et al. Ann Intern Med. 2007;146:477-485.

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

Hypoglycemia With Exenatide:Mono and Dual Combination Therapy




30 Weeks3


N 233 336 377 233


SU Exe +SU

TZD Exe +TZD

Exenatide: Adverse Events

Adverse Events*

Patients (%)

Monotherapy + Met and/or SU + TZD ± Met

Exe(n=155)

PBO(n=77)

Exe(n=963)

PBO(n=483)

Exe(n=121)

PBO(n=112)

Nausea 8 0 44 18 40 15

Vomiting 4 0 13 4 13 1

Diarrhea 13 6 6 3

Feeling Jittery 9 4

Dizziness 9 6

Headache 9 6

Dyspepsia 3 0 6 3 7 1

Asthenia 4 2

GERD 3 1 3 0

Hyperhidrosis 3 1

*Occurring in ≥2% of patients receiving exenatide

Byetta (exenatide) injection prescribing information. San Diego, CA: Amylin Pharmaceuticals, Inc. 2011 .

*P<0.0001 vs monotherapy. **P<0.0001 vs dual therapy. ***P=0.0015 vs glargine.†All liraglutide dosages shown are 1.8 mg QD.

1. Garber A, et al. Lancet. 2009;373:473-481. 2. Nauck M, et al. Diabetes Care. 2009;32:84-90. 3. Pratley RE, et al. Lancet. 2010;375:1447-1456. 4. Marre M, et al. Diabet Med. 2009;26:268-278. 5. Zinman B, et al. Diabetes Care. 2009;32:1224-1230.

6. Russell-Jones D, et al. Diabetologia. 2009;52:2046-2055.

Glucose Control With Liraglutide With/Without Oral Agents

A

1C (

%)

-1.6-1.4-1.2

-1-0.8-0.6-0.4-0.2

00.20.4

-0.51

-0.98 -0.9

-0.44 -0.5

-1.09-1.14-1.00

-1.50

-1.13

-1.50-1.33

0.090.23

-0.24

Monotherapy vs Glimepiride52 Weeks1




26 Weeks4

Add-on toMet + TZD26 Weeks5

Add-on toMet + SU

26 Weeks6

N 746 1091 665 1041 821 581

Treatment Glim Lir Met Glim +

Met

Lira +Met

Sit +Met

Lira +Met

SU Rosi +

SU

Lira +SU

Rosi +

Met

Lira +Rosi +

Met

Met +SU

Glar +Met +

SU

Lira +Met +

SU

Baseline A1C (%)

8.4 8.3 8.4 8.4 8.4 8.5 8.4 8.4 8.4 8.5 8.4 8.6 8.3 8.2 8.3

*** ***

*******

*

*P<0.0001 vs glargine, rosiglitazone, sitagliptin, or SU. **P<0.01 vs metformin. ***P<0.05 vs SU.†All liraglutide dosages shown are 1.8 mg QD.

1. Garber A, et al. Lancet. 2009;373:473-481. 2. Nauck M, et al. Diabetes Care. 2009;32:84-90. 3. Pratley RE, et al. Lancet. 2010;375:1447-1456. 4. Marre M, et al. Diabet Med. 2009;26:268-278. 5. Zinman B, et al. Diabetes Care. 2009;32:1224-1230.

6. Russell-Jones D, et al. Diabetologia. 2009;52:2046-2055.

-4

-3

-2

-1

0

1

2

3

1.10 1.00

-0.96

2.10

0.60

1.60

-2.50 -2.80-3.38

-0.20

-2.00 -1.80-1.50

-0.10-0.42

W

eigh

t (kg

) Weight Reduction With Liraglutide: Mono

and Dual Combination Therapy

* ****

*

*

***





26 Weeks4


Add-on toMet + SU

26 Weeks6

N 746 1091 665 1041 821 581


Met

Lira +Met

Sit +Met

Lira +Met

SU Rosi +

SU

Lira +SU

Rosi +

Met

Lira +Rosi +

Met

Met +SU

Glar +Met +

SU

Lira +Met +

SU

*

Blood Pressure Changes With Liraglutide

-6

-5

-4

-3

-2

-1

0

1

-0.7

0.4

-0.9 -0.9 -1.1

0.5

-3.6

-2.3

-0.7

-2.8

-5.6

-4.0

-1.8-2.3

S

ysto

lic B

P

(mm

Hg)

**

**




Add-on to Sulfonylurea26 Weeks4,5


Add-on toMet + SU

26 Weeks7

N 746 1091 665 1041 821 581


Met

Lira +Met

Sit +Met

Lira +Met

SU Rosi +

SU

Lira +SU

Rosi +

Met

Lira +Rosi +

Met

Met +SU

Glar +Met +

SU

Lira +Met +

SU

*P<0.05 vs comparator.†All liraglutide dosages shown are 1.8 mg QD.

1. Garber A, et al. Lancet. 2009;373:473-481. 2. Nauck M, et al. Diabetes Care. 2009;32:84-90.3. Pratley RE, et al. Lancet. 2010;375:1447-1456. 4. Marre M, et al. Diabet Med. 2009;26:268-278.

5. Colagiuri S, et al. Diabetes. 2008;57(suppl 2): Abstr. 554-P. 6. Zinman B, et al. Diabetes Care. 2009;32:1224-1230. 7. Russell-Jones D, et al. Diabetologia. 2009;52:2046-2055

*P<0.01 vs active comparator.†All liraglutide dosages shown are 1.8 mg QD.

1. Garber A, et al. Lancet. 2009;373:473-481. 2. Nauck M, et al. Diabetes Care. 2009;32:84-90. 3. Pratley RE, et al. Lancet. 2010;375:1447-1456. 4. Marre M, et al. Diabet Med. 2009;26:268-278.

Hypoglycemia With Liraglutide:Mono and Dual Combination Therapy




Add-on to Sulfonylurea26 Weeks4

N 746 1091 665 1041

Treatment† Glim Lira Met Glim +Met

Lira +Met

Sit +Met

Lira +Met

SU Rosi +SU

Lira +SU

*

Pat

ient

s R

epor

ting

Hyp

ogly

cem

ia (

%)

**

Liraglutide: Adverse Events

Adverse Events*

Patients (%)

Monotherapy + Met + Glim + Met + TZD

Lir(n=497)

Glim(n=248)

Lir(n=724)

PBO(n=121

)Lir

(n=695)PBO

(n=114)Lir

(n=355)PBO

(n=175)

Nausea 28.4 8.5 15.2 4.1 7.5 1.8 34.6 8.6

Diarrhea 17.1 8.9 10.9 4.1 7.2 1.8 14.1 6.3

Vomiting 10.9 3.6 6.5 0.8 12.4 2.9

Constipation 9.9 4.8 5.3 0.9 5.1 1.1

Headache 9.1 9.3 9.0 6.6 8.2 4.6

Dyspepsia 5.2 0.9

*Adverse events of interest occurring in ≥5% of patients receiving liraglutide.

Victoza (liraglutide) injection prescribing information. Princeton, NJ: Novo Nordisk Inc. 2012.

*Metformin, sulfonylurea, thiazolidinedione, or combination of any 2 of these agents.†Metformin, sulfonylurea, metformin + sulfonylurea, or metformin + pioglitazone.

1. Drucker DJ, et al. Lancet. 2008;372:1240-1250. 2. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258.3. Bergenstal RM, et al. Lancet. 2010;376:431-439. 4. Diamant M, et al. Lancet. 2010;375:2234-2243.

5. Buse JB, et al. Lancet. 2013;381:117-124.

Glucose Control With Exenatide ER

A1C

(%

)

Add-on toOAs*

30 Weeks1

Monotherapy vs OAs

26 Weeks2


Add-on toMet +/- SU26 Weeks4

Add-on toOAs†

26 Weeks5

N 258 820 514 456 911

Treatment Exe BID

Exe ER

Sit Pio Met Exe ER

Sit Pio Exe ER

Glar + OAs

Exe ER + OAs

Lira + OAs

Exe ER + OAs

Baseline A1C (%)

8.3 8.3 8.5 8.5 8.6 8.5 8.5 8.5 8.6 8.3 8.3 8.4 8.5

P<0.001 P<0.0001P<0.01P=0.017 P=0.02




Add-on toOAs*

30 Weeks1

Monotherapy vs OAs

26 Weeks2



Add-on toOAs†

26 Weeks5

N 258 820 514 456 911

Treatment (mg/day)

Exe BID

Exe ER

Sit Pio Met Exe ER

Sit Pio Exe ER

Glar +

OAs

Exe ER + OAs

Lira +

OAs

Exe ER + OAs

P<0.0001

W

eigh

t (kg

)

Weight Reduction With Exenatide ER

P<0.001P<0.001




0

5

10

15

20

25

30

35

6.1 3.7 3.0

31.0

8.95.4 4.1

1.0

13.011.0

3.15.2

1.0

Add-on toOAs*

30 Weeks1

Monotherapy vs OAs

26 Weeks2



Add-on toOAs†

26 Weeks5

N 258 820 514 456 911

Treatment Exe BID

Exe ER

Sit Pio Met Exe ER

Sit Pio Exe ER

Glar +

OAs

Exe ER + OAs

Lira +

OAs

Exe ER + OAs

Pat

ient

s re

port

ing

hypo

glyc

emia

(%

)

Hypoglycemia With Exenatide ER

Exenatide Extended Release: Adverse Events

Adverse Events*

Patients (%)

Monotherapy + Met + Met +/- SU

Exe ER(n=248)

Sit(n=163)

Pio(n=163)

Met(n=246)

Exe ER(n=160)

Sit(n=166)

Pio (n=165)

Exe ER(n=233)

Glar(n=233)

Nausea 11.3 3.7 4.3 6.9 24.4 9.6 4.8 12.9 1.3

Diarrhea 10.9 5.5 3.7 12.6 20.0 9.6 7.3 9.4 4.0

Injection site reaction 10.5 6.7 3.7 10.2 5.0 4.8 1.2 6.0 0

Constipation 8.5 2.5 1.8 3.3 6.3 3.6 1.2

Headache 8.1 9.2 8.0 12.2 9.4 9.0 5.5 9.9 7.6

Dyspepsia 7.3 1.8 4.9 3.3 5.0 3.6 2.4

Vomiting 11.3 2.4 3.0

Fatigue 5.6 0.6 3.0

*Adverse events of interest occurring in ≥5% of patients receiving exenatide extended release.

Bydureon (exenatide extended release) injection prescribing information.San Diego, CA: Amylin Pharmaceuticals, Inc. 2012.

*Estimated glumerular filtration rate 30-50 mL/min/1.73 m2.

**P<0.001 vs placebo. ***P<0.05 vs placebo.†Met criteria for noninferiority and superiority (upper limit of confidence interval <0.0%).

1. Stenlof K, et al. Diabetes Obes Metab. 2013;15:372-382. 2. Rosenstock J, et al. Diabetes Care. 2012;35:1232-1238.3. Schernthaner G, et al. Diabetes Care. 2013;April 5 epub ahead of print. 4. Yale J-F, et al. Diabetes Obes Metab. 2013;15:463-473.

Glucose Control With Canagliflozin

A1C

(%

)

-1.2

-1

-0.8

-0.6

-0.4

-0.2

0

0.2

0.40.14

-0.74 -0.66

-0.03

-0.77 -0.76

-1.03

-0.33

-1.03-0.92

-0.44

-0.22



Add-on toMetformin + SU

52 Weeks3

Add-on toOAs +/- Insulin in

CKD*26 Weeks4

N 584 451 755 269

Treatment (mg/day)

PBO Can 100

Can 300

PBO Sit Can 100

Can 300

Sit Can 300

PBO Can 100

Can 300

Baseline A1C (%)

8.0 8.1 8.0 7.8 7.6 7.8 7.7 8.1 8.1 8.0 7.9 8.0

****

******

†

*****


**P<0.001 vs placebo. †P<0.001 vs sitagliptin.


Weight Change With Canagliflozin

-4-3.5

-3-2.5

-2-1.5

-1-0.5

00.5

-0.5 -0.5

0.1 0.2

-2.5-2.3 -2.3

-1.2

-3.4-3.0

-1.4-0.9




52 Weeks3


CKD*26 Weeks4

N 584 451 755 269

Treatment (mg/day)

PBO Can 100

Can 300

PBO Sit Can 100

Can 300

Sit Can 300

PBO Can 100

Can 300

**

****

** † W

eigh

t (kg

)


**P<0.001 vs comparator.


Blood Pressure Change With Canagliflozin

-7-6-5-4-3-2-1012

0.4

-0.8

0.9

-0.3

-3.3

1.0

-5.1-6.1

-5.0

-3.6

-6.4

-1.3




52 Weeks3

Add-on toOAs +/- Insulin

in CKD*26 Weeks4

N 584 451 755 269

Treatment (mg/day)

PBO Can 100

Can 300

PBO Sit Can 100

Can 300

Sit Can 300

PBO Can 100

Can 300

S

ysto

lic B

P

(mm

Hg)

**

**

**


**P<0.001 vs placebo. ***P<0.05 vs placebo.†Met criteria for noninferiority and superiority (upper limit of confidence interval <0.0%).


Hypoglycemia With Canagliflozin

0

10

20

30

40

50

60

35

4136

4 2

43

53

30

51

2




52 Weeks3


CKD*26 Weeks4

N 584 451 755 269

Treatment (mg/day)

PBO Can 100

Can 300

PBO Sit Can 100

Can 300

Sit Can 300

PBO Can 100

Can 300

Pat

ient

s re

port

ing

hypo

glyc

emia

(%

)

Canagliflozin: Adverse Events

Adverse Events*

Patients (%)

Canagliflozin 100 mg(n=833)

Canagliflozin 300 mg(n=834)

Placebo(n=646)

Female genital mycotic infections 10.4 11.4 3.2

Urinary tract infections 5.9 4.3 4.0

Increased urination 5.3 4.6 0.8

Male genital mycotic infections 4.2 3.7 0.6

Vulvovaginal pruritis 1.6 3.0 0

Thirst 2.8 2.3 0.2

Constipation 1.8 2.3 0.9

Nausea 2.2 2.3 1.5

*Adverse events of interest occurring in ≥2% of patients receiving canagliflozin.

Invokana (canagliflozin) prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2013.

Documents

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