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Glycemic Management in Type 2 Diabetes

Glycemic Management in Type 2 Diabetes. Efficacy and Safety of Antihyperglycemic Therapies Introduced Since 2004. DPP-4 Inhibitors. DPP-4 Inhibitors. FDA-Approved Agents Alogliptin Linagliptin Saxagliptin Sitagliptin. Key Features Oral administration

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Glycemic Management in Type 2 Diabetes

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

  2. DPP-4 Inhibitors

  3. DPP-4 Inhibitors FDA-Approved Agents • Alogliptin • Linagliptin • Saxagliptin • Sitagliptin Key Features • Oral administration • Increase endogenous GLP-1 and GIP levels • Increase glucose-dependent insulin secretion • Suppress glucagon production DPP-4, dipeptidyl peptidase 4; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide 1. Garber AJ, et al. EndocrPract. 2013;19(suppl 2):1-48.

  4. Glucose Controlwith DPP-4 Inhibitors Placebo-Adjusted Change from Baseline (Not Head-to-Head Trials) Placebo-adjusted  A1C (%) ‡ *SU + metformin. †With or without metformin. ‡Absolute change from baseline (active-controlled trial). 1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Del Prato S, et al. Diabetes ObesMetab. 2011;13:258-267.3. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 4. NauckMA, et al. Diabetes ObesMetab. 2007;9:194-205. 5. Nauck MA, et al. Int J ClinPract. 2009;63:46-55. 6. TaskinenMR, et al. Diabetes ObesMetab. 2011;13:65-74. 7. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 8. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 9. Pratley RE, et al. Diabetes ObesMetab. 2009;11:167-176. 10. Owens DR, et al. Diabet Med. 2011;28:1352-61. 11. ChacraAR, et al. Int J Clin Pract. 2009;63:1395-1406. 12. Hermansen K, et al. Diabetes ObesMetab. 2007;9:733-745.

  5. Weight Changewith DPP-4 Inhibitors Absolute Change from Baseline (Not Head-to-Head Trials)  Weight (kg) NR NR NR, value not reported. *SU + metformin. †With or without metformin. 1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Del Prato S, et al. Diabetes ObesMetab. 2011;13:258-267.3. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 4. NauckMA, et al. Diabetes ObesMetab. 2007;9:194-205. 5. Nauck MA, et al. Int J ClinPract. 2009;63:46-55. 6. TaskinenMR, et al. Diabetes ObesMetab. 2011;13:65-74. 7. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 8. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 9. Pratley RE, et al. Diabetes ObesMetab. 2009;11:167-176. 10. Owens DR, et al. Diabet Med. 2011;28:1352-61. 11. ChacraAR, et al. Int J Clin Pract. 2009;63:1395-1406. 12. Hermansen K, et al. Diabetes ObesMetab. 2007;9:733-745.

  6. Hypoglycemiawith DPP-4 Inhibitors Percentage of Patients Reporting Hypoglycemia (Not Head-to-Head Trials) Patients (%) NR NR NR, value not reported. *SU + metformin. †With or without metformin. 1. DeFronzo RA, et al. Diabetes Care. 2008;31:2315–2317. 2. Del Prato S, et al. Diabetes ObesMetab. 2011;13:258-267.3. Rosenstock J, et al. Curr Med Res Opin. 2009;25:2401-2411. 4. NauckMA, et al. Diabetes ObesMetab. 2007;9:194-205. 5. Nauck MA, et al. Int J ClinPract. 2009;63:46-55. 6. TaskinenMR, et al. Diabetes ObesMetab. 2011;13:65-74. 7. DeFronzo RA, et al. Diabetes Care. 2009;32:1649-1655. 8. Charbonnel B, et al. Diabetes Care. 2006;29:2638-2643. 9. Pratley RE, et al. Diabetes ObesMetab. 2009;11:167-176. 10. Owens DR, et al. Diabet Med. 2011;28:1352-61. 11. ChacraAR, et al. Int J Clin Pract. 2009;63:1395-1406. 12. Hermansen K, et al. Diabetes ObesMetab. 2007;9:733-745.

  7. Safety Considerationswith DPP-4 Inhibitors Garber AJ, et al. EndocrPract. 2013;19(suppl 2):1-48.ADA/EASD/IDF statement concerning the use of incretin therapy and pancreatic disease [news release]. Alexandria, VA: American Diabetes Association, European Association for the Study of Diabetes, International Diabetes Federation; June 28, 2013. http://www.diabetes.org/newsroom/press-releases/2013/recommendations-for.html.

  8. Glucose Control With Alogliptin  A1C (%) * * * * * * • P<0.001 vs comparator(s). • 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.

  9. Weight Change With Alogliptin  Weight (kg) * • P<0.01 vs comparator. • 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.

  10. Hypoglycemia With Alogliptin Patients Reporting Hypoglycemia (%) • 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 ClinPract. 2009;63:46-55.4. Pratley RE, et al. Diabetes ObesMetab. 2009;11:167-176. 5. Bosi E, et al. Diabetes ObesMetab. 2011;13:1088-1096.6. Rosenstock J, et al. Diabetes ObesMetab. 2009;11:1145-1152.

  11. Alogliptin:Warnings and Adverse Events Nesina (alogliptin) prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; 2013.

  12. Glucose Control With Linagliptin  A1C (%) * * * * † * 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.

  13. Weight Changes With Linagliptin  Weight (kg) * * 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.

  14. Hypoglycemia With Linagliptin Patients Reporting Hypoglycemia (%) 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.

  15. Linagliptin:Warnings and Adverse Events Tradjenta (linagliptin) prescribing information. Ridgefield, CT: Boehringer Ingelheim, Inc.; 2014.

  16. Glucose Control With Saxagliptin  A1C (%) * * * * * 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.

  17. Weight Changes With Saxagliptin * Weight (kg) *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.

  18. Hypoglycemia With Saxagliptin Patients Reporting Hypoglycemia (%) 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.

  19. Saxagliptin: Adverse Events Onglyza (saxagliptin) prescribing information. Princeton, NJ: Bristol-Meyers Squibb. 2013.

  20. Glucose Control With Sitagliptin  A1C (%) * * † * *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. DobsAS, et al. J Diabetes. 2013;5:68-79.

  21. Weight Changes With Sitagliptin  Weight (kg) * † *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.

  22. Hypoglycemia With Sitagliptin Patients Reporting Hypoglycemia (%) 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.

  23. Selected Adverse Events With Sitagliptin: Pooled Data 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.

  24. GLP-1 Receptor Agonists

  25. GLP-1 Receptor Agonists FDA-Approved Agents • Albiglutide • Exenatide • Exenatide ER • Liraglutide Key Features • Injectable administration • Mimic action of native GLP-1 • Increase glucose-dependent insulin secretion • Suppress glucagon production • Slow gastric emptying ER, extended release; GLP-1, glucagon-like peptide 1. Garber AJ, et al. EndocrPract. 2013;19(suppl 2):1-48.

  26. Glucose Controlwith GLP-1 Receptor Agonists Placebo-Adjusted Change from Baseline (Not Head-to-Head Trials) Placebo-adjusted  A1C (%) ‡ ‡ ‡ ‡ ‡ ‡ *Metformin with or without SU or TZD. †Metformin with or without SU. ‡Absolute change from baseline (active-controlled trial). 1. Tanzeum (albiglutide) injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2014.2. Moretto TJ, et al. ClinTher. 2008;30:1448-1460. 3. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 4. Garber A, et al. Lancet. 2009;373:473-481. 5. AhrénB, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epub ahead of print]. 6. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 7. Bergenstal RM, et al. Lancet. 2010;376:431-439. 8. Pratley RE, et al. Lancet. 2010;375:1447-1456. 9. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 10. BuseJB, et al. Diabetes Care. 2004;27:2628-2635. 11. Diamant M, et al. Lancet. 2010;375:2234-2243. 12. MarreM, et al. Diabet Med. 2009;26:268-278.

  27. Weight Change with GLP-1 Receptor Agonists Absolute Change from Baseline (Not Head-to-Head Trials)  Weight (kg) *Metformin with or without SU or TZD. †Metformin with or without SU. 1. Tanzeum (albiglutide) injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2014.2. Moretto TJ, et al. ClinTher. 2008;30:1448-1460. 3. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 4. Garber A, et al. Lancet. 2009;373:473-481. 5. AhrénB, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epub ahead of print]. 6. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 7. Bergenstal RM, et al. Lancet. 2010;376:431-439. 8. Pratley RE, et al. Lancet. 2010;375:1447-1456. 9. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 10. BuseJB, et al. Diabetes Care. 2004;27:2628-2635. 11. Diamant M, et al. Lancet. 2010;375:2234-2243. 12. MarreM, et al. Diabet Med. 2009;26:268-278.

  28. Hypoglycemia with GLP-1 Receptor Agonists Percentage of Patients Reporting Hypoglycemia (Not Head-to-Head Trials) Patients (%) *Metformin with or without SU or TZD. †Metformin with or without SU. 1. Tanzeum (albiglutide) injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2014.2. Moretto TJ, et al. ClinTher. 2008;30:1448-1460. 3. Russell-Jones D, et al. Diabetes Care. 2012;35:252-258. 4. Garber A, et al. Lancet. 2009;373:473-481. 5. AhrénB, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epub ahead of print]. 6. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. 7. Bergenstal RM, et al. Lancet. 2010;376:431-439. 8. Pratley RE, et al. Lancet. 2010;375:1447-1456. 9. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 10. BuseJB, et al. Diabetes Care. 2004;27:2628-2635. 11. Diamant M, et al. Lancet. 2010;375:2234-2243. 12. MarreM, et al. Diabet Med. 2009;26:268-278.

  29. Safety Considerationswith GLP1 Receptor Agonists ER, extended release. Garber AJ, et al. EndocrPract. 2013;19(suppl 2):1-48.ADA/EASD/IDF statement concerning the use of incretin therapy and pancreatic disease [news release]. Alexandria, VA: American Diabetes Association, European Association for the Study of Diabetes, International Diabetes Federation; June 28, 2013. http://www.diabetes.org/newsroom/press-releases/2013/recommendations-for.html.

  30. Glucose Control With Albiglutide  A1C (%) * ** * *P<0.0001 vs placebo. **P<0.001 vs active compatators. †All albiglutide dosages shown are 50 mg once weekly. 1. Tanzeum (albiglutide) injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2014.2. Ahrén B, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epubahead of print]. 3. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 4. Rosenstock J, et al. Diabetes Care. 2014 Jun 4. pii: DC_140001. [Epub ahead of print].

  31. Weight Change With Albiglutide  Weight (kg) * * ** *P<0.0001 vs glimepiride or lispro. **P<0.0001 vs albiglutide. †All albiglutide dosages shown are 50 mg once weekly. 1. Nauck M, et al. Diabetes. 2013;62(suppl 2): Abstr. 55-LB.2. Ahrén B, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epubahead of print]. 3. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 4. Rosenstock J, et al. Diabetes Care. 2014 Jun 4. pii: DC_140001. [Epub ahead of print].

  32. Blood Pressure Change With Albiglutide  Systolic BP (mmHg) Decrease of <1 mmHg in both groups *P<0.0001 vs glimepiride or lispro. **P<0.0001 vs albiglutide. †All albiglutide dosages shown are 50 mg once weekly. 1. AhrénB, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epubahead of print].2. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297.

  33. Hypoglycemia With Albiglutide Patients with documented symptomatic hypoglycemia (%) *P<0.0001 vs glimepiride or lispro. **P<0.0001 vs albiglutide. †All albiglutide dosages shown are 50 mg once weekly. 1. Nauck M, et al. Diabetes. 2013;62(suppl 2): Abstr. 55-LB.2. Ahrén B, et al. Diabetes Care. 2014 Jun 4. pii: DC_140024. [Epubahead of print]. 3. Pratley RE, et al. Lancet Diabetes Endocrinol. 2014;2:289-297. 4. Rosenstock J, et al. Diabetes Care. 2014 Jun 4. pii: DC_140001. [Epub ahead of print].

  34. Albiglutide: Adverse Events Tanzeum (albiglutide) injection prescribing information. Research Triangle Park, NC: GlaxoSmithKline; 2014.

  35. Glucose Control With Exenatide  A1C (%) * * * * * *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.

  36. Weight Reduction With Exenatide  Weight (kg) * * * ** * * *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.

  37. Blood Pressure Changes With Exenatide  Systolic BP (mmHg) * *P<0.05 vs placebo. Moretto TJ, et al. Clin Ther. 2008;30:1448-1460.

  38. Hypoglycemia With Exenatide Patients Reporting Hypoglycemia (%) †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.

  39. Exenatide: Adverse Events Byetta (exenatide) injection prescribing information. Wilmington, DE: AstraZeneca Pharmaceuticals LP. 2013 .

  40. Glucose Control With Exenatide ER  A1C (%) P=0.02 P=0.017 P<0.0001 P<0.01 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;372:1240-1250. 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.

  41. Weight Reduction With Exenatide ER  Weight (kg) P<0.0001 P<0.001 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;372:1240-1250. 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.

  42. Hypoglycemia With Exenatide ER Patients reporting hypoglycemia (%) *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.

  43. Exenatide Extended Release: Adverse Events Bydureon (exenatide extended release) injection prescribing information.Wilmington, DE: AstraZeneca Pharmaceuticals LP. 2014.

  44. Glucose Control With Liraglutide  A1C (%) * * * ** ** ** *** ** *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.

  45. Weight Reduction With Liraglutide ***  Weight (kg) * * * * * * ** *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.

  46. Blood Pressure Changes With Liraglutide  Systolic BP (mmHg) * * * * *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

  47. Hypoglycemia With Liraglutide Patients Reporting Hypoglycemia (%) * * * *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.

  48. Liraglutide: Adverse Events Victoza (liraglutide) injection prescribing information. Princeton, NJ: Novo Nordisk Inc. 2013.

  49. SGLT2 Inhibitors

  50. SGLT2 Inhibitors FDA-Approved Agents • Canagliflozin • Dapagliflozin Key Features • Oral administration • Inhibit reabsorption of glucose into the bloodstream from renal fluid SGLT2, sodium-glucose cotransporter 2. DeFronzo RA, et al. Diabetes ObesMetab. 2012;14:5-14.

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