Glycemic Management in Type 2 Diabetes

Report
Glycemic Management in
Type 2 Diabetes
Efficacy and Safety of
Antihyperglycemic Therapies
Introduced Since 2004
1
Glucose Control With Sitagliptin: Selected
Mono and Combination Therapy Studies
Monotherapy
vs Glipizide
52 Weeks1
Initial Combo
w/ Metformin
24 Weeks2
Add-on to
Metformin
24 Weeks3
Add-on to
Insulin
24 Weeks4
1172
1091
701
641
N
Add-on to
Add-on to
Pioglitazone vs Rosiglitazone +
Met + Pio
Metformin
5
12 Months
54 Weeks6
151
Treatment
Sit
Glip
Sit
Met
Sit+
Met
Met
Sit+
Met
Ins
Sit+
Ins
Baseline A1C
(%)
7.5
7.5
8.9
8.7
8.8
8.0
8.0
8.6
8.7
278
Met + Sit +
Pio
Pio
8.4
8.5
Rosi + Sit +
Met Rosi
+
Met
8.7
8.8
0
0
 A1C (%)
-0.02
-0.3
-0.5
-0.67 -0.67
-0.66
-0.67
*
-1
-1.13
-1.5
-2
-0.6
*
-1.1
-1.4 -1.4
†
-1.9
*
*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..
Weight Changes With Sitagliptin: Selected
Mono and Combination Therapy Studies
Monotherapy Monotherapy Add-on to
24 Weeks1
52 Weeks2 Pioglitazone
24 Weeks3
N
741
PBO
Sit
Glip
353
Sit
Pio
Sit +
Pio
Add-on to
Insulin
24 Weeks5
Add-on to
Pio vs Met +
Pio
12 Months6
441
641
151
Glim
Sit +
Glim
Ins
Sit +
Ins
Met +
Pio
Sit +
Pio
 Weight (kg)
Treatment
793
Add-on to
Glimepiride
24 Weeks4
*
†
*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.
Hypoglycemia With Sitagliptin:
Selected Studies
Sitagliptin vs
Glipizide
52 weeks1
Initial Combo
w/ Metformin
24 Weeks2
Add-on to
Metformin
24 Weeks3
Add-on to
Pioglitazone
24 Weeks4
Add-on to
Glimepiride
24 Weeks5
Add-on to
Insulin
24 Weeks6
793
1091
701
353
441
641
N
Treatment
Sit
Patients Reporting
Hypoglycemia (%)
35
Glip
PBO Met
Sit +
Met
Met Sit +
Met
Pio
Sit + Glim Sit + Sit +
Pio
Glim Glim +
Met
Ins
Sit +
Ins
32
30
25
20
16.4
16.0
15
10
5
0
7.5
4.9
2.2
0.6 1.1
2.1 1.3
0
1.1
8.0
2.8
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.
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.
Glucose Control With Saxagliptin:
Mono and Combination Therapy
Monotherapy
24 Weeks1
Initial Combo
w/ Metformin
24 Weeks2
Add-on to
Metformin
24 Weeks3
Add-on to
Metformin
18 Weeks4
Add-on to
Glyburide vs
Uptitration
24 Weeks5
Add-on to
TZD
24 Weeks6
401
1306
743
801
768
565
N
Treatment
 A1C (%)
Baseline A1C (%)
PBO
Sax
Met
Sax +
Met
Met
Sax +
Met
Sit +
Met
Sax +
Met
Gly
Sax +
Gly
TZD
Sax +
TZD
7.9
8.0
9.4
9.4
8.1
8.1
7.7
7.7
8.4
8.5
8.2
8.4
*
*
*
*
*
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.
Weight Changes With Saxagliptin:
Mono and Combination Therapy
Monotherapy Initial Combo
24 Weeks1 w/ Metformin
24 Weeks2
N
401
Weight (kg)
Treatment
PBO
Add-on to
Metformin
24 Weeks3
Add-on to
Metformin
18 Weeks4
Add-on to
Glyburide vs
Uptitration
24 Weeks5
Add-on to
TZD
24 Weeks6
743
801
768
565
1306
Sax
Met
Sax +
Met
Met
Sax +
Met
Sit +
Met
Sax +
Met
Gly
Sax +
Gly
TZD
Sax +
TZD
*
*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.
Hypoglycemia With Saxagliptin:
Mono and Combination Therapy
Monotherapy Initial Combo
24 Weeks1 w/ Metformin
24 Weeks2
N
401
PBO
Add-on to
Metformin
18 Weeks4
Add-on to
Glyburide vs
Uptitration
24 Weeks5
Add-on to
TZD
24 Weeks6
743
801
768
565
1306
Sax
Met
Sax +
Met
Met
Sax +
Met
Sit +
Met
Sax +
Met
Gly
Sax +
Gly
TZD
Sax +
TZD
Patients Reporting
Hypoglycemia (%)
Treatment
Add-on to
Metformin
24 Weeks3
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.
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.
Glucose Control With Linagliptin:
Mono and Combination Therapy
Monotherapy Initial Combo Initial Combo
24 Weeks1
w/ Metformin w/ Pioglitazone
24 Weeks2
24 Weeks3
N
Treatment
 A1C (%)
Baseline A1C
(%)
Add-on to
Metformin
24 Weeks4
Add-on to
Metformin
2 Years5
Add-on to
Metformin +
SU
24 Weeks6
1055
503
791
389
700
1552
PBO Lin
Lin Met Lin + Lin +
HD Met Met
LD HD
Pio Lin +
Pio
Met Lin +
Met
Glim + Lin +
Met
Met
8.7
8.6
8.0
8.0
8.0
8.5
8.7
8.7
8.6
*
8.1
*
*
7.7
7.7
Met +
SU
Lin +
Met +
SU
8.1
8.2
*
†
* 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.
Weight Changes With Linagliptin
Initial Combo w/
Metformin
24 Weeks1
Initial Combo
w/ Pioglitazone
24 Weeks2
Add-on to
Metformin
24 Weeks3
Add-on to
Metformin
2 Years4
791
389
700
1552
Met Lin +
Met
Glim Lin +
+ Met Met
N
Lin
Met Lin + Lin +
HD Met Met
LD
HD
Pio
Lin +
Pio
 Weight (kg)
Treatment
*
* P<0.0001 vs comparator.
HD, high-dose metformin (1000 mg twice daily); LD, low-dose metformin (500 mg twice daily).
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
Monotherapy Initial Combo Initial Combo
24 Weeks1
w/ Metformin w/ Pioglitazone
24 Weeks2
24 Weeks3
N
Treatment
Add-on to
Metformin
24 Weeks4
Add-on to
Metformin
2 Years5
Add-on to
Metformin +
SU
24 Weeks6
1055
503
791
389
700
1552
PBO Lin
Lin Met Lin + Lin +
HD Met Met
LD HD
Pio Lin +
Pio
Met Lin +
Met
Glim + Lin +
Met
Met
40
Met +
SU
Lin +
Met +
SU
36
Patients Reporting
Hypoglycemia (%)
35
30
22.7
25
20
14.8
15
10
5
0
7
3.4 3.5
0.6 0.3
0
0
0 1.2
2.8
0.6
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.
Incidence of Adverse Events With
Linagliptin
Adverse Events*
Patients (%)
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.
Tradjenta (linagliptin) prescribing information. Ridgefield, CT: Boehringer Ingelheim, Inc.; 2012.
Glucose Control With Alogliptin:
Mono and Combination Therapy
Monotherapy Initial Combo
26 Weeks1 w/ Pioglitazone
26 Weeks2
N
Treatment
 A1C (%)
Baseline A1C
(%)
329
PBO Alo
7.9
7.9
Add-on to
Metformin
26 Weeks3
Add-on to
Glyburide
26 Weeks4
Add-on to
Met + Pio
52 Weeks5
Add-on to
Insulin +/- Met
26 Weeks6
527
500
803
390
Pio Alo Alo +
Pio
Met Alo +
Met
Gly Alo +
Gly
Met + Alo +
Pio Met +
Pio
8.8
8.0
8.1
655
8.8
8.8
*
7.9
*
8.1
*
8.1
8.3
*
Ins +/- Alo +
Met Ins +/Met
9.3
9.3
*
*
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.
Weight Change With Alogliptin
Monotherapy Initial Combo
26 Weeks1 w/ Pioglitazone
26 Weeks2
N
PBO Alo
655
Pio Alo Alo +
Pio
 Weight (kg)
Treatment
329
Add-on to
Metformin
26 Weeks3
Add-on to
Glyburide
26 Weeks4
Add-on to
Met + Pio
52 Weeks5
Add-on to
Insulin +/- Met
26 Weeks6
527
500
803
390
Met Alo +
Met
Gly Alo +
Gly
Met + Alo +
Pio Met +
Pio
Ins +/- Alo +
Met Ins +/Met
*
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.
Hypoglycemia With Alogliptin
Monotherapy
26 Weeks1,2
Add-on to
Metformin
26 Weeks3
Add-on to
Glyburide
26 Weeks4
Add-on to
Met + Pio
52 Weeks5
Add-on to Insulin
+/- Met
26 Weeks6
329
527
500
803
390
N
PBO
Alo
Met
Alo +
Met
Gly
Alo +
Gly
Met +
Pio
Alo + Met +
Pio
Ins
+/- Met
Alo + Ins +/Met
Patients Reporting
Hypoglycemia (%)
Treatment
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.
Incidence of Adverse Events With
Alogliptin
Adverse Events*
Patients (%)
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.
Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013.
Glucose Control With Exenatide
With/Without Oral Agents
Monotherapy
24 Weeks1
Add-on to
Metformin
30 Weeks2
Add-on to
Sulfonylurea
30 Weeks3
233
336
377
N
Treatment†
PBO
Exe
Baseline A1C (%)
Add-on to TZD
Add-on to
Add-on to Met +
16 Weeks4
Metformin + SU SU vs Glargine
30 Weeks5
26 Weeks6
233
733
Met
Exe +
Met
SU
Exe +
SU
TZD
Exe +
TZD
Met +
SU
Exe +
Met +
SU
Glar +
Met +
SU
Exe +
Met +
SU
8.2
8.2
8.7
8.6
7.9
7.9
8.5
8.5
8.3
8.2
0.4
0.12
0.1
0.2
551
0.2
0.09
 A1C (%)
0
-0.2
-0.4
-0.2
-0.6
-0.8
-1
-0.9
-1.2
*
-0.8
*
-0.86
*
-0.89
-0.9
*
*
-1.1
-1.1
*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.
Weight Reduction With Exenatide: Mono
and Dual Combination Therapy
Monotherapy
24 Weeks1
Add-on to
Metformin
30 Weeks2
Add-on to
Sulfonylurea
30 Weeks3
233
336
377
N
PBO
Exe
Met
Exe +
Met
SU
233
Exe +
SU
TZD
733
Exe +
TZD
Met +
SU
551
Exe +
Met +
SU
Glar +
Met +
SU
Exe +
Met +
SU
 Weight (kg)
Treatment†
Add-on to TZD
Add-on to
Add-on to Met +
16 Weeks4
Metformin + SU SU vs Glargine
30 Weeks5
26 Weeks6
*
*
*
*
*
**
*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.
Blood Pressure Changes With
Exenatide
Monotherapy
24 Weeks
N
233
PBO
Exe 10 μg BID
 Systolic BP
(mmHg)
Treatment
*
*P<0.05 vs placebo.
Moretto TJ, et al. Clin Ther. 2008;30:1448-1460.
Hypoglycemia With Exenatide:
Mono and Dual Combination Therapy
Monotherapy
24 Weeks1
Add-on to Metformin
30 Weeks2
Add-on to
Sulfonylurea
30 Weeks3
Add-on to TZD
16 Weeks4
233
336
377
233
N
PBO
Exe
Met
Exe +
Met
SU
Exe +
SU
TZD
Exe +
TZD
Patients Reporting
Hypoglycemia (%)
Treatment†
†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.
Exenatide: 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
6
3
7
1
Asthenia
4
2
GERD
3
1
3
0
Hyperhidrosis
3
1
Adverse Events*
Dyspepsia
3
0
*Occurring in ≥2% of patients receiving exenatide
Byetta (exenatide) injection prescribing information. San Diego, CA: Amylin Pharmaceuticals, Inc. 2011 .
Glucose Control With Liraglutide
With/Without Oral Agents
Monotherapy vs
Glimepiride
52 Weeks1
Add-on to
Metformin
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Sulfonylurea
26 Weeks4
Add-on to
Met + TZD
26 Weeks5
Add-on to
Met + SU
26 Weeks6
N
746
1091
665
1041
821
581
Treatment
Glim
Lir
Met Glim Lira +
+
Met
Met
8.4
8.3
8.4
Baseline
A1C (%)
8.4
8.4
Sit + Lira +
Met Met
8.5
8.4
0.5
SU
8.4
Rosi Lira +
+
SU
SU
8.4
8.5
Rosi Lira + Met + Glar + Lira +
+ Rosi + SU Met + Met +
Met Met
SU
SU
8.4
8.6
8.3
8.2
8.3
0.23
0.09
 A1C (%)
0
-0.5
-0.24
-0.44
-0.51
-1
-1.5
-2
-1.14
*
-0.98 -1.00
*
-0.5
-0.9
-1.09
-1.13
-1.50
**
*
**
-1.50
**
-1.33
**
***
*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.
Weight Reduction With Liraglutide: Mono
and Dual Combination Therapy
Monotherapy vs
Glimepiride
52 Weeks1
Add-on to
Metformin
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Sulfonylurea
26 Weeks4
Add-on to
Met + TZD
26 Weeks5
Add-on to
Met + SU
26 Weeks6
N
746
1091
665
1041
821
581
Treatment
Glim
Lir
Met Glim Lira +
+
Met
Met
Sit + Lira +
Met Met
 Weight (kg)
1
Rosi Lira +
+
SU
SU
Rosi Lira + Met + Glar + Lira +
+ Rosi + SU Met + Met +
Met Met
SU
SU
***
2.10
3
2
SU
1.60
1.00
1.10
0.60
0
-0.10
-1
-0.96
-2
-2.50
-4
*
-0.42
*
-1.50
-3
-0.20
-2.80
*
**
-3.38
-2.00
-1.80
*
*
*
*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.
Blood Pressure Changes
With Liraglutide
N
Treatment
Monotherapy vs
Glimepiride
52 Weeks1
Add-on to
Metformin
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Sulfonylurea
26 Weeks4,5
Add-on to
Met + TZD
26 Weeks6
Add-on to
Met + SU
26 Weeks7
746
1091
665
1041
821
581
Glim
Lir
Met Glim Lira +
+
Met
Met
SU
Rosi Lira +
+
SU
SU
Rosi Lira + Met + Glar + Lira +
+ Rosi + SU Met + Met +
Met Met
SU
SU
0.5
0.4
1
 Systolic BP
(mmHg)
Sit + Lira +
Met Met
0
-1
-0.7
-0.9 -0.7
-2
-1.8
-3
-4
-5
-6
-3.6
-2.3
*
-0.9
-2.3
-1.1
-2.8
-4.0
*
-5.6
*
†All
*
*P<0.05 vs comparator.
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
Hypoglycemia With Liraglutide:
Mono and Dual Combination Therapy
Monotherapy
52 Weeks1
Add-on to Metformin
26 Weeks2
Add-on to Metformin
26 Weeks3
Add-on to Sulfonylurea
26 Weeks4
746
1091
665
1041
N
Patients Reporting
Hypoglycemia (%)
Treatment†
Glim
Lira
Met
Glim +
Met
Lira +
Met
Sit +
Met
Lira +
Met
SU
Rosi +
SU
Lira +
SU
*
*
*
*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.
Liraglutide: Adverse Events
Patients (%)
Monotherapy
+ Met
+ Glim
+ Met + TZD
Adverse
Events*
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
5.1
1.1
Headache
9.1
9.3
8.2
4.6
Dyspepsia
5.3
9.0
0.9
6.6
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.
Glucose Control With Exenatide ER
Add-on to
OAs*
30 Weeks1
Monotherapy vs
OAs
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Met +/- SU
26 Weeks4
Add-on to
OAs†
26 Weeks5
258
820
514
456
911
N
Treatment
Exe Exe
BID ER
Sit
Pio
Met Exe
ER
Sit
Pio
Exe
ER
Baseline
A1C (%)
8.3
8.5
8.5
8.6
8.5
8.5
8.6
8.5
8.3
8.3
Lira + Exe ER
OAs + OAs
8.4
8.5
 A1C (%)
8.3
Glar + Exe ER
OAs
+ OAs
P<0.01
P<0.001
P<0.0001
P=0.017
P=0.02
*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.
Weight Reduction With Exenatide ER
N
Monotherapy vs
OAs
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Met +/- SU
26 Weeks4
Add-on to
OAs†
26 Weeks5
258
820
514
456
911
Glar Exe
+ ER +
OAs OAs
Lira Exe
+ ER +
OAs OAs
Exe Exe
BID ER
Sit
Pio
Met Exe
ER
Sit
Pio
Exe
ER
 Weight (kg)
Treatment
(mg/day)
Add-on to
OAs*
30 Weeks1
P<0.001
P<0.001
P<0.0001
*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.
Hypoglycemia With Exenatide ER
N
Patients reporting
hypoglycemia (%)
Treatment
Add-on to
OAs*
30 Weeks1
Monotherapy vs
OAs
26 Weeks2
Add-on to
Metformin
26 Weeks3
Add-on to
Met +/- SU
26 Weeks4
Add-on to
OAs†
26 Weeks5
258
820
514
456
911
Glar Exe
+ ER +
OAs OAs
Lira Exe
+ ER +
OAs OAs
Exe Exe
BID ER
Sit
Pio
Met Exe
ER
Sit
Pio
Exe
ER
35
31.0
30
25
20
13.0
15
10
5
8.9
6.1 5.4
5.2
3.1 3.7 4.1
3.0
11.0
1.0 1.0
0
*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.
Exenatide Extended Release:
Adverse Events
Patients (%)
Adverse
Events*
Monotherapy
+ Met
+ Met +/- SU
Exe ER
Sit
Pio
Met
Exe ER
Sit
Pio
Exe ER
Glar
(n=248)
(n=163)
(n=163)
(n=246)
(n=160)
(n=166)
(n=165)
(n=233)
(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.
Glucose Control With Canagliflozin
Monotherapy
26 Weeks1
Add-on to
Metformin
12 Weeks2
Add-on to
Metformin + SU
52 Weeks3
Add-on to
OAs +/- Insulin in
CKD*
26 Weeks4
584
451
755
269
N
Treatment
(mg/day)
Baseline
A1C (%)
 A1C (%)
0.2
PBO
Can
100
Can
300
PBO
Sit
Can
100
Can
300
Sit
Can
300
PBO
Can
100
Can
300
8.0
8.1
8.0
7.8
7.6
7.8
7.7
8.1
8.1
8.0
7.9
8.0
0.14
0
-0.03
-0.2
-0.22
-0.4
-0.33
-0.6
-0.8
-1
-1.2
**
-0.66
-0.74 -0.76
-0.77
-1.03
**
**
**
***
-0.92
**
-0.44
**
-1.03
†
*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.
Weight Change With Canagliflozin
N
 Weight (kg)
Treatment
(mg/day)
0.5
0
-0.5
-1
-1.5
-2
-2.5
-3
-3.5
-4
Monotherapy
26 Weeks1
Add-on to
Metformin
12 Weeks2
Add-on to
Metformin + SU
52 Weeks3
Add-on to
OAs +/- Insulin in
CKD*
26 Weeks4
584
451
755
269
PBO
Can
100
Can
300
PBO
Sit
Can
100
Can
300
Sit
Can
300
Can
100
Can
300
0.2
0.1
-0.5
PBO
-0.5
-0.9
-2.3
-2.5
**
-1.2
**
-3.4
**
-1.4
-2.3
-3.0
†
**
*Estimated glumerular filtration rate 30-50 mL/min/1.73 m2.
**P<0.001 vs placebo. †P<0.001 vs sitagliptin.
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.
Blood Pressure Change With
Canagliflozin
N
Treatment
(mg/day)
Monotherapy
26 Weeks1
Add-on to
Metformin
12 Weeks2
Add-on to
Metformin + SU
52 Weeks3
Add-on to
OAs +/- Insulin
in CKD*
26 Weeks4
584
451
755
269
PBO
Can
100
Can
300
PBO
Sit
 Systolic BP
(mmHg)
2
Can
100
Can
300
1.0
0.4
Sit
Can
300
PBO
Can
100
Can
300
0.9
0
-4
-3.3
-6
**
-8
-0.3
-1.3 -0.8
-2
-3.6
-5.0
**
-5.1
**
-6.1 -6.4
*Estimated glumerular filtration rate 30-50 mL/min/1.73 m2.
**P<0.001 vs comparator.
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.
Hypoglycemia With Canagliflozin
Monotherapy
26 Weeks1
Add-on to
Metformin
12 Weeks2
Add-on to
Metformin + SU
52 Weeks3
Add-on to
OAs +/- Insulin in
CKD*
26 Weeks4
584
451
755
269
N
Patients reporting
hypoglycemia (%)
Treatment
(mg/day)
PBO
Can
100
Can
300
PBO
Sit
Can
100
Can
300
Sit
Can
300
PBO
60
Can
100
53
50
41
40
Can
300
51
43
36
30
20
10
0
3
4
3
2
5
2
0
*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.
Canagliflozin: Adverse Events
Patients (%)
Adverse Events*
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.

similar documents