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

*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: Goldstein BJ, et al. Diabetes Care. 2007;30: Charbonnel B, et al. Diabetes Care. 2006;29: Vilsbøll T, et al. Diabetes Obes Metab. 2010;12: Derosa G, et al. Metab Clin Exp. 2010;59: Dobs AS, et al. J Diabetes. 2013;5:  A1C (%) Glucose Control With Sitagliptin: Selected Mono and Combination Therapy Studies Monotherapy vs Glipizide 52 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Insulin 24 Weeks 4 Add-on to Pioglitazone vs Met + Pio 12 Months 5 Add-on to Rosiglitazone + Metformin 54 Weeks 6 N TreatmentSitGlipSitMetSit+ Met MetSit+ Met InsSit+ Ins Met + Pio Sit + Pio Rosi + Met Sit + Rosi + Met Baseline A1C (%) * * * †

*P<0.001 vs glipizide; † P<0.05 vs sitagliptin. 1. Aschner P, et al. Diabetes Care. 2006;29: Nauck MA, et al. Diabetes Obes Metab. 2007;9: Rosenstock J, et al. Clin Ther. 2006;28: Hermansen K, et al. Diabetes Obes Metab. 2007;9: Vilsbøll T, et al. Diabetes Obes Metab. 2010;12: Derosa G, et al. Metab Clin Exp. 2010;59:  Weight (kg) Weight Changes With Sitagliptin: Selected Mono and Combination Therapy Studies Monotherapy 24 Weeks 1 Monotherapy 52 Weeks 2 Add-on to Pioglitazone 24 Weeks 3 Add-on to Glimepiride 24 Weeks 4 Add-on to Insulin 24 Weeks 5 Add-on to Pio vs Met + Pio 12 Months 6 N TreatmentPBOSitGlipSitPioSit + Pio GlimSit + Glim InsSit + Ins Met + Pio Sit + Pio † *

1. Nauck MA, et al. Diabetes Obes Metab. 2007;9: Goldstein BJ, et al. Diabetes Care. 2007;30: Charbonnel B, et al. Diabetes Care. 2006;29: Rosenstock J, et al. Clin Ther. 2006;28: Hermansen K, et al. Diabetes Obes Metab. 2007;9: Vilsbøll T, et al. Diabetes Obes Metab. 2010;12: Hypoglycemia With Sitagliptin: Selected Studies Sitagliptin vs Glipizide 52 weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Pioglitazone 24 Weeks 4 Add-on to Glimepiride 24 Weeks 5 Add-on to Insulin 24 Weeks 6 N TreatmentSitGlipPBOMetSit + Met MetSit + Met PioSit + Pio GlimSit + Glim Sit + Glim + Met InsSit + Ins Patients Reporting Hypoglycemia (%)

Incidence of Selected Adverse Events With Sitagliptin: Pooled Data Adverse EventIncidence per 100 patient-yearsDifference (95% CI) Sitagliptin 100 mgNonexposed Constipation (0.1, 1.4) Diarrhea (-3.6, -1.0) Headache (-0.7, 1.4) Nasopharyngitis (-0.3, 2.1) Pancreatitis (-0.20, 0.14) Rash (-0.1, 0.8) Upper respiratory tract infection (-1.6, 1.0) Williams-Herman D, et al. BMC Endocr Disord. 2010;10(7). Engel SS, et al. Int J Clin Pract. 2010;64:

P< vs comparator. 1. Rosenstock J, et al. Curr Med Res Opin. 2009;25: Jadzinsky M, et al. Diabetes Obes Metab. 2009;11: DeFronzo RA, et al. Diabetes Care. 2009;32: Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26: Chacra AR, et al. Int J Clin Pract. 2009;63: Hollander P, et al. J Clin Endocrinol Metab. 2009;94: Glucose Control With Saxagliptin: Mono and Combination Therapy Monotherapy 24 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Metformin 18 Weeks 4 Add-on to Glyburide vs Uptitration 24 Weeks 5 Add-on to TZD 24 Weeks 6 N TreatmentPBOSaxMetSax + Met MetSax + Met Sit + Met Sax + Met GlySax + Gly TZDSax + TZD Baseline A1C (%) *  A1C (%) * * * *

*P=0.01 vs glyburide uptitration. 1. Rosenstock J, et al. Curr Med Res Opin. 2009;25: Jadzinsky M, et al. Diabetes Obes Metab. 2009;11: DeFronzo RA, et al. Diabetes Care. 2009;32: Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26: Chacra AR, et al. Int J Clin Pract. 2009;63: Hollander P, et al. J Clin Endocrinol Metab. 2009;94:  Weight (kg) Weight Changes With Saxagliptin: Mono and Combination Therapy Monotherapy 24 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Metformin 18 Weeks 4 Add-on to Glyburide vs Uptitration 24 Weeks 5 Add-on to TZD 24 Weeks 6 N TreatmentPBOSaxMetSax + Met MetSax + Met Sit + Met Sax + Met GlySax + Gly TZDSax + TZD *

1. Rosenstock J, et al. Curr Med Res Opin. 2009;25: Jadzinsky M, et al. Diabetes Obes Metab. 2009;11: DeFronzo RA, et al. Diabetes Care. 2009;32: Scheen AJ, et al. Diabetes Metab Res Rev. 2010;26: Chacra AR, et al. Int J Clin Pract. 2009;63: Hollander P, et al. J Clin Endocrinol Metab. 2009;94: Hypoglycemia With Saxagliptin: Mono and Combination Therapy Monotherapy 24 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Metformin 18 Weeks 4 Add-on to Glyburide vs Uptitration 24 Weeks 5 Add-on to TZD 24 Weeks 6 N TreatmentPBOSaxMetSax + Met MetSax + Met Sit + Met Sax + Met GlySax + Gly TZDSax + TZD Patients Reporting Hypoglycemia (%)

Incidence of Adverse Events With Saxagliptin Adverse Events*Patients (%) Saxagliptin 5 mgPlacebo Headache Upper respiratory tract infection Urinary tract infection *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

* P< vs comparator. † P< 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: Haak T, et al. Diabetes Obes Metab. 2012;14: Gomis R, et al. Diabetes Obes Metab. 2011;13: Taskinen MR, et al. Diabetes Obes Metab. 2011;13: Gallwitz B, et al. Lancet. 2012;380: Owens DR, et al. Diabet Med. 2011;28: Glucose Control With Linagliptin: Mono and Combination Therapy Monotherapy 24 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Initial Combo w/ Pioglitazone 24 Weeks 3 Add-on to Metformin 24 Weeks 4 Add-on to Metformin 2 Years 5 Add-on to Metformin + SU 24 Weeks 6 N TreatmentPBOLin Met HD Lin + Met LD Lin + Met HD PioLin + Pio MetLin + Met Glim + Met Lin + Met Met + SU Lin + Met + SU Baseline A1C (%)  A1C (%) * * * * †

Weight Changes With Linagliptin Initial Combo w/ Metformin 24 Weeks 1 Initial Combo w/ Pioglitazone 24 Weeks 2 Add-on to Metformin 24 Weeks 3 Add-on to Metformin 2 Years 4 N TreatmentLinMet HD Lin + Met LD Lin + Met HD PioLin + Pio MetLin + Met Glim + Met Lin + Met  Weight (kg) * P< 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: Gomis R, et al. Diabetes Obes Metab. 2011;13: Taskinen MR, et al. Diabetes Obes Metab. 2011;13: Gallwitz B, et al. Lancet. 2012;380: *

Hypoglycemia With Linagliptin: Mono and Combination Therapy Patients Reporting Hypoglycemia (%) Monotherapy 24 Weeks 1 Initial Combo w/ Metformin 24 Weeks 2 Initial Combo w/ Pioglitazone 24 Weeks 3 Add-on to Metformin 24 Weeks 4 Add-on to Metformin 2 Years 5 Add-on to Metformin + SU 24 Weeks 6 N TreatmentPBOLin Met HD Lin + Met LD Lin + Met HD PioLin + Pio MetLin + Met Glim + Met Lin + Met Met + SU Lin + Met + SU 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: Haak T, et al. Diabetes Obes Metab. 2012;14: Gomis R, et al. Diabetes Obes Metab. 2011;13: Taskinen MR, et al. Diabetes Obes Metab. 2011;13: Gallwitz B, et al. Lancet. 2012;380: Owens DR, et al. Diabet Med. 2011;28:

Incidence of Adverse Events With Linagliptin Tradjenta (linagliptin) prescribing information. Ridgefield, CT: Boehringer Ingelheim, Inc.; Adverse Events*Patients (%) Linagliptin 5 mg (n=3625) Placebo (n=2176) Nasopharyngitis Diarrhea Cough *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– Rosenstock J, et al. Diabetes Care. 2010;33:2406– Nauck MA, et al. Int J Clin Pract. 2009;63: Pratley RE, et al. Diabetes Obes Metab. 2009;11: Bosi E, et al. Diabetes Obes Metab. 2011;13: Rosenstock J, et al. Diabetes Obes Metab. 2009;11: Glucose Control With Alogliptin: Mono and Combination Therapy Monotherapy 26 Weeks 1 Initial Combo w/ Pioglitazone 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Glyburide 26 Weeks 4 Add-on to Met + Pio 52 Weeks 5 Add-on to Insulin +/- Met 26 Weeks 6 N TreatmentPBOAloPioAloAlo + Pio MetAlo + Met GlyAlo + Gly Met + Pio Alo + Met + Pio Ins +/- Met Alo + Ins +/- Met Baseline A1C (%)  A1C (%) * * * * * *

P<0.01 vs comparator. 1.DeFronzo RA, et al. Diabetes Care. 2008;31:2315– Rosenstock J, et al. Diabetes Care. 2010;33:2406– Nauck MA, et al. Int J Clin Pract. 2009;63: Pratley RE, et al. Diabetes Obes Metab. 2009;11: Bosi E, et al. Diabetes Obes Metab. 2011;13: Rosenstock J, et al. Diabetes Obes Metab. 2009;11: Weight Change With Alogliptin Monotherapy 26 Weeks 1 Initial Combo w/ Pioglitazone 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Glyburide 26 Weeks 4 Add-on to Met + Pio 52 Weeks 5 Add-on to Insulin +/- Met 26 Weeks 6 N TreatmentPBOAloPioAloAlo + Pio MetAlo + Met GlyAlo + Gly Met + Pio Alo + Met + Pio Ins +/- Met Alo + Ins +/- Met  Weight (kg) *

1.DeFronzo RA, et al. Diabetes Care. 2008;31:2315– Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; Nauck MA, et al. Int J Clin Pract. 2009;63: Pratley RE, et al. Diabetes Obes Metab. 2009;11: Bosi E, et al. Diabetes Obes Metab. 2011;13: Rosenstock J, et al. Diabetes Obes Metab. 2009;11: Hypoglycemia With Alogliptin Monotherapy 26 Weeks 1,2 Add-on to Metformin 26 Weeks 3 Add-on to Glyburide 26 Weeks 4 Add-on to Met + Pio 52 Weeks 5 Add-on to Insulin +/- Met 26 Weeks 6 N TreatmentPBOAloMetAlo + Met GlyAlo + Gly Met + Pio Alo + Met + Pio Ins +/- Met Alo + Ins +/- Met Patients Reporting Hypoglycemia (%)

Incidence of Adverse Events With Alogliptin Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; Adverse Events*Patients (%) Alogliptin 25 mg (n=5902) Placebo (n=2926) Active comparator (n=2257) Nasopharyngitis Headache Upper respiratory tract infection *Occurring in ≥4% of patients receiving alogliptin 25 mg and more commonly than in placebo-treated patients.

 A1C (%) 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: DeFronzo RA et al. Diabetes Care. 2005;28: Buse JB, et al. Diabetes Care. 2004;27: Zinman B, et al. Ann Intern Med. 2007;146: Kendall DM et al. Diabetes Care. 2005;28: Heine RJ, et al. Ann Intern Med. 2005;143: Monotherapy 24 Weeks 1 Add-on to Metformin 30 Weeks 2 Add-on to Sulfonylurea 30 Weeks 3 Add-on to TZD 16 Weeks 4 Add-on to Metformin + SU 30 Weeks 5 Add-on to Met + SU vs Glargine 26 Weeks 6 N Treatment†PBOExeMetExe + Met SUExe + SU TZDExe + TZD Met + SU Exe + Met + SU Glar + Met + SU Exe + Met + SU Baseline A1C (%) * * * * *

 Weight (kg) Weight Reduction With Exenatide: Mono and Dual Combination Therapy *P<0.05 vs comparator. **P< vs glargine. † All exenatide dosages shown are 10 μg BID. 1. Moretto TJ, et al. Clin Ther. 2008;30: DeFronzo RA et al. Diabetes Care. 2005;28: Buse JB, et al. Diabetes Care. 2004;27: Zinman B, et al. Ann Intern Med. 2007;146: Kendall DM et al. Diabetes Care. 2005;28: Heine RJ, et al. Ann Intern Med. 2005;143: Monotherapy 24 Weeks 1 Add-on to Metformin 30 Weeks 2 Add-on to Sulfonylurea 30 Weeks 3 Add-on to TZD 16 Weeks 4 Add-on to Metformin + SU 30 Weeks 5 Add-on to Met + SU vs Glargine 26 Weeks 6 N Treatment†PBOExeMetExe + Met SUExe + SU TZDExe + 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:  Systolic BP (mmHg) Blood Pressure Changes With Exenatide Monotherapy 24 Weeks N233 TreatmentPBOExe 10 μg BID *

† All exenatide dosages shown are 10 μg BID. 1. Moretto TJ, et al. Clin Ther. 2008;30: DeFronzo RA et al. Diabetes Care. 2005;28: Buse JB, et al. Diabetes Care. 2004;27: Zinman B, et al. Ann Intern Med. 2007;146: Patients Reporting Hypoglycemia (%) Hypoglycemia With Exenatide: Mono and Dual Combination Therapy Monotherapy 24 Weeks 1 Add-on to Metformin 30 Weeks 2 Add-on to Sulfonylurea 30 Weeks 3 Add-on to TZD 16 Weeks 4 N Treatment†PBOExeMetExe + Met SUExe + SU TZDExe + 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 Vomiting Diarrhea13663 Feeling Jittery94 Dizziness96 Headache96 Dyspepsia Asthenia42 GERD3130 Hyperhidrosis31 *Occurring in ≥2% of patients receiving exenatide Byetta (exenatide) injection prescribing information. San Diego, CA: Amylin Pharmaceuticals, Inc

*P< vs monotherapy. **P< vs dual therapy. ***P= vs glargine. † All liraglutide dosages shown are 1.8 mg QD. 1. Garber A, et al. Lancet. 2009;373: Nauck M, et al. Diabetes Care. 2009;32: Pratley RE, et al. Lancet. 2010;375: Marre M, et al. Diabet Med. 2009;26: Zinman B, et al. Diabetes Care. 2009;32: Russell-Jones D, et al. Diabetologia. 2009;52: Glucose Control With Liraglutide With/Without Oral Agents  A1C (%) Monotherapy vs Glimepiride 52 Weeks 1 Add-on to Metformin 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Sulfonylurea 26 Weeks 4 Add-on to Met + TZD 26 Weeks 5 Add-on to Met + SU 26 Weeks 6 N TreatmentGlimLirMetGlim + Met Lira + Met Sit + Met Lira + Met SURosi + SU Lira + SU Rosi + Met Lira + Rosi + Met Met + SU Glar + Met + SU Lira + Met + SU Baseline A1C (%) * ** * *** *

*P< 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: Nauck M, et al. Diabetes Care. 2009;32: Pratley RE, et al. Lancet. 2010;375: Marre M, et al. Diabet Med. 2009;26: Zinman B, et al. Diabetes Care. 2009;32: Russell-Jones D, et al. Diabetologia. 2009;52:  Weight (kg) Weight Reduction With Liraglutide: Mono and Dual Combination Therapy * * * ** * * *** Monotherapy vs Glimepiride 52 Weeks 1 Add-on to Metformin 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Sulfonylurea 26 Weeks 4 Add-on to Met + TZD 26 Weeks 5 Add-on to Met + SU 26 Weeks 6 N TreatmentGlimLir MetGlim + Met Lira + Met Sit + Met Lira + Met SURosi + SU Lira + SU Rosi + Met Lira + Rosi + Met Met + SU Glar + Met + SU Lira + Met + SU *

Blood Pressure Changes With Liraglutide  Systolic BP (mmHg) * * * * Monotherapy vs Glimepiride 52 Weeks 1 Add-on to Metformin 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Sulfonylurea 26 Weeks 4,5 Add-on to Met + TZD 26 Weeks 6 Add-on to Met + SU 26 Weeks 7 N TreatmentGlimLir MetGlim + Met Lira + Met Sit + Met Lira + Met SURosi + 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: Nauck M, et al. Diabetes Care. 2009;32: Pratley RE, et al. Lancet. 2010;375: Marre M, et al. Diabet Med. 2009;26: Colagiuri S, et al. Diabetes. 2008;57(suppl 2): Abstr. 554-P. 6. Zinman B, et al. Diabetes Care. 2009;32: Russell-Jones D, et al. Diabetologia. 2009;52:

*P<0.01 vs active comparator. † All liraglutide dosages shown are 1.8 mg QD. 1. Garber A, et al. Lancet. 2009;373: Nauck M, et al. Diabetes Care. 2009;32: Pratley RE, et al. Lancet. 2010;375: Marre M, et al. Diabet Med. 2009;26: Hypoglycemia With Liraglutide: Mono and Dual Combination Therapy Monotherapy 52 Weeks 1 Add-on to Metformin 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Sulfonylurea 26 Weeks 4 N Treatment†GlimLiraMetGlim + Met Lira + Met Sit + Met Lira + Met SURosi + SU Lira + SU * Patients Reporting Hypoglycemia (%) * *

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 Diarrhea Vomiting Constipation Headache Dyspepsia *Adverse events of interest occurring in ≥5% of patients receiving liraglutide. Victoza (liraglutide) injection prescribing information. Princeton, NJ: Novo Nordisk Inc

*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: Russell-Jones D, et al. Diabetes Care. 2012;35: Bergenstal RM, et al. Lancet. 2010;376: Diamant M, et al. Lancet. 2010;375: Buse JB, et al. Lancet. 2013;381: Glucose Control With Exenatide ER  A1C (%) Add-on to OAs* 30 Weeks 1 Monotherapy vs OAs 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Met +/- SU 26 Weeks 4 Add-on to OAs † 26 Weeks 5 N TreatmentExe BID Exe ER SitPioMetExe ER SitPioExe ER Glar + OAs Exe ER + OAs Lira + OAs Exe ER + OAs Baseline A1C (%) P<0.001 P< P<0.01 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: Russell-Jones D, et al. Diabetes Care. 2012;35: Bergenstal RM, et al. Lancet. 2010;376: Diamant M, et al. Lancet. 2010;375: Buse JB, et al. Lancet. 2013;381: Add-on to OAs* 30 Weeks 1 Monotherapy vs OAs 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Met +/- SU 26 Weeks 4 Add-on to OAs † 26 Weeks 5 N Treatment (mg/day) Exe BID Exe ER SitPioMetExe ER SitPioExe ER Glar + OAs Exe ER + OAs Lira + OAs Exe ER + OAs P<  Weight (kg) Weight Reduction With Exenatide ER P<0.001

*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: Russell-Jones D, et al. Diabetes Care. 2012;35: Bergenstal RM, et al. Lancet. 2010;376: Diamant M, et al. Lancet. 2010;375: Buse JB, et al. Lancet. 2013;381: Add-on to OAs* 30 Weeks 1 Monotherapy vs OAs 26 Weeks 2 Add-on to Metformin 26 Weeks 3 Add-on to Met +/- SU 26 Weeks 4 Add-on to OAs † 26 Weeks 5 N TreatmentExe BID Exe ER SitPioMetExe ER SitPioExe ER Glar + OAs Exe ER + OAs Lira + OAs Exe ER + OAs Patients reporting hypoglycemia (%) 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 Diarrhea Injection site reaction Constipation Headache Dyspepsia Vomiting Fatigue *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

*Estimated glumerular filtration rate mL/min/1.73 m 2. **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: Rosenstock J, et al. Diabetes Care. 2012;35: Schernthaner G, et al. Diabetes Care. 2013;April 5 epub ahead of print. 4. Yale J-F, et al. Diabetes Obes Metab. 2013;15: Glucose Control With Canagliflozin  A1C (%) Monotherapy 26 Weeks 1 Add-on to Metformin 12 Weeks 2 Add-on to Metformin + SU 52 Weeks 3 Add-on to OAs +/- Insulin in CKD* 26 Weeks 4 N Treatment (mg/day) PBOCan 100 Can 300 PBOSitCan 100 Can 300 SitCan 300 PBOCan 100 Can 300 Baseline A1C (%) ** † ***

*Estimated glumerular filtration rate mL/min/1.73 m 2. **P<0.001 vs placebo. † P<0.001 vs sitagliptin. 1. Stenlof K, et al. Diabetes Obes Metab. 2013;15: Rosenstock J, et al. Diabetes Care. 2012;35: Schernthaner G, et al. Diabetes Care. 2013;April 5 epub ahead of print. 4. Yale J-F, et al. Diabetes Obes Metab. 2013;15: Weight Change With Canagliflozin Monotherapy 26 Weeks 1 Add-on to Metformin 12 Weeks 2 Add-on to Metformin + SU 52 Weeks 3 Add-on to OAs +/- Insulin in CKD* 26 Weeks 4 N Treatment (mg/day) PBOCan 100 Can 300 PBOSitCan 100 Can 300 SitCan 300 PBOCan 100 Can 300 ** †  Weight (kg)

*Estimated glumerular filtration rate mL/min/1.73 m 2. **P<0.001 vs comparator. 1. Stenlof K, et al. Diabetes Obes Metab. 2013;15: Rosenstock J, et al. Diabetes Care. 2012;35: Schernthaner G, et al. Diabetes Care. 2013;April 5 epub ahead of print. 4. Yale J-F, et al. Diabetes Obes Metab. 2013;15: Blood Pressure Change With Canagliflozin Monotherapy 26 Weeks 1 Add-on to Metformin 12 Weeks 2 Add-on to Metformin + SU 52 Weeks 3 Add-on to OAs +/- Insulin in CKD* 26 Weeks 4 N Treatment (mg/day) PBOCan 100 Can 300 PBOSitCan 100 Can 300 SitCan 300 PBOCan 100 Can 300  Systolic BP (mmHg) **

*Estimated glumerular filtration rate mL/min/1.73 m 2. **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: Rosenstock J, et al. Diabetes Care. 2012;35: Schernthaner G, et al. Diabetes Care. 2013;April 5 epub ahead of print. 4. Yale J-F, et al. Diabetes Obes Metab. 2013;15: Hypoglycemia With Canagliflozin Monotherapy 26 Weeks 1 Add-on to Metformin 12 Weeks 2 Add-on to Metformin + SU 52 Weeks 3 Add-on to OAs +/- Insulin in CKD* 26 Weeks 4 N Treatment (mg/day) PBOCan 100 Can 300 PBOSitCan 100 Can 300 SitCan 300 PBOCan 100 Can 300 Patients reporting hypoglycemia (%)

Canagliflozin: Adverse Events Adverse Events* Patients (%) Canagliflozin 100 mg (n=833) Canagliflozin 300 mg (n=834) Placebo (n=646) Female genital mycotic infections Urinary tract infections Increased urination Male genital mycotic infections Vulvovaginal pruritis Thirst Constipation Nausea *Adverse events of interest occurring in ≥2% of patients receiving canagliflozin. Invokana (canagliflozin) prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc