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Section 5 What’s on the Horizon: Emerging Therapies
 -Cell Adaptation and Failure: Opportunities for Prevention and Treatment of Type 2 Diabetes
Disclosure ,[object Object],[object Object],[object Object]
Future Therapies: Incretins ,[object Object],[object Object],[object Object],Drucker DJ.  Diabetes Care . 2003;26:2929-2940.
Glucagon-Like Peptide-1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Drucker DJ.  Curr Pharm Des . 2001;7:1399-1412. Drucker DJ.  Mol Endocrinol . 2003;17:161-171.
Insulin and GLP-1 Responses  to Meals Ørskov C et al.  Scand J Gastroenterol . 1996;31:665-670. Insulin (pmol/L) GLP-1 (pmol/L) 0 20 40 0 200 400 9  AM 1  PM 7  PM 10  PM 9  AM Hours Meal Meal Meal
GLP-1 Release Is Reduced in Type 2 Diabetes Toft-Nielsen MB et al.  J Clin Endocrinol Metab . 2001;86:3717-3723. GLP-1 (pmol/L) 0 5 10 15 20 0 60 120 180 240 NGT (n=33) IGT (n=15) Time (min) * * * * * * * * Type 2 diabetes (n=54) * P <0.05 between type 2 diabetes  and NGT groups. Meal
Effect of GLP-1 on the   -Cell ,[object Object],[object Object],[object Object],[object Object]
GLP-1 Infusion Improves   -Cell Insulin Secretion C-peptide (pmol/L) Zander M et al.  Lancet . 2002;359:824-830. 0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 0 20 40 60 80 Time (min) Saline  GLP-1  0 weeks 1 week 6 weeks 10 30 50 70 90
GLP-1 and First-Phase  Insulin Secretion Insulin pmol/L 1,800 750 Time (min) Time (min) 1,500 1,200 900 600 300 0 600 450 300 150 0 -15 0 15 30 45 60 -15 0 15 30 45 60 IV Glucose IV Glucose Data are mean    SEM Subjects Without Diabetes Subjects With Diabetes Quddusi S et al.  Diabetes Care.  2003;26:791-798. Saline Control GLP-1-Acute GLP-1-Prolonged (2 minutes) (3 hours)
Exenatide: Effect on the   -Cell ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],Buse JB et al.  Diabetes Care . 2004;27:2628-2635. DeFronzo RA et al.  Diabetes Care . 2005;28:1092-1100. Kendall DM et al.  Diabetes Care . 2005;28:1083-1091. Nielsen LL et al.  Regul Pept . 2004;117:77-88.
Exenatide: Effects on Glycemic Control in Combination With Current Oral Therapies   Exenatide  + Met   Exenatide  + SU   Exenatide  + Met + SU Placebo 5   g BID 10   g BID 0.40 -1.20 -1.00 -0.80 -0.60 -0.40 -0.20 0.00 0.20 Change in A1C from baseline (%) * † * † † † Buse JB et al.  Diabetes Care.  2004;27:2628-2635.  DeFronzo RA et al.  Diabetes Care.  2005;28:1092-1100.  Kendall DM et al.  Diabetes Care.  2005;28:1083-1091.  * P <0.001 vs placebo;  † P <0.0001   vs placebo . Met=metformin; SU=sulfonylurea.
Exenatide: Proportion of  Patients Achieving A1C   7% 0 5 10 15 20 25 30 35 40 45 50 Ex + Met Ex + SU Ex + Met + SU Proportion achieving A1C   7%   † † † † * Buse JB et al.  Diabetes Care.  2004;27:2628-2635.  DeFronzo RA et al.  Diabetes Care.  2005;28:1092-1100.  Kendall DM et al.  Diabetes Care.  2005;28:1083-1091.  * P <0.01 vs placebo; † P <0.0001 vs placebo. Ex=exenatide; Met=metformin;  SU=sulfonylurea. † Placebo 5   g BID 10   g BID
Summary ,[object Object],[object Object],[object Object]

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Ndei Beta Cell Slide Kit Future Therapies

  • 1. Section 5 What’s on the Horizon: Emerging Therapies
  • 2.  -Cell Adaptation and Failure: Opportunities for Prevention and Treatment of Type 2 Diabetes
  • 3.
  • 4.
  • 5.
  • 6. Insulin and GLP-1 Responses to Meals Ørskov C et al. Scand J Gastroenterol . 1996;31:665-670. Insulin (pmol/L) GLP-1 (pmol/L) 0 20 40 0 200 400 9 AM 1 PM 7 PM 10 PM 9 AM Hours Meal Meal Meal
  • 7. GLP-1 Release Is Reduced in Type 2 Diabetes Toft-Nielsen MB et al. J Clin Endocrinol Metab . 2001;86:3717-3723. GLP-1 (pmol/L) 0 5 10 15 20 0 60 120 180 240 NGT (n=33) IGT (n=15) Time (min) * * * * * * * * Type 2 diabetes (n=54) * P <0.05 between type 2 diabetes and NGT groups. Meal
  • 8.
  • 9. GLP-1 Infusion Improves  -Cell Insulin Secretion C-peptide (pmol/L) Zander M et al. Lancet . 2002;359:824-830. 0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 0 20 40 60 80 Time (min) Saline GLP-1 0 weeks 1 week 6 weeks 10 30 50 70 90
  • 10. GLP-1 and First-Phase Insulin Secretion Insulin pmol/L 1,800 750 Time (min) Time (min) 1,500 1,200 900 600 300 0 600 450 300 150 0 -15 0 15 30 45 60 -15 0 15 30 45 60 IV Glucose IV Glucose Data are mean  SEM Subjects Without Diabetes Subjects With Diabetes Quddusi S et al. Diabetes Care. 2003;26:791-798. Saline Control GLP-1-Acute GLP-1-Prolonged (2 minutes) (3 hours)
  • 11.
  • 12. Exenatide: Effects on Glycemic Control in Combination With Current Oral Therapies Exenatide + Met Exenatide + SU Exenatide + Met + SU Placebo 5  g BID 10  g BID 0.40 -1.20 -1.00 -0.80 -0.60 -0.40 -0.20 0.00 0.20 Change in A1C from baseline (%) * † * † † † Buse JB et al. Diabetes Care. 2004;27:2628-2635. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. Kendall DM et al. Diabetes Care. 2005;28:1083-1091. * P <0.001 vs placebo; † P <0.0001 vs placebo . Met=metformin; SU=sulfonylurea.
  • 13. Exenatide: Proportion of Patients Achieving A1C  7% 0 5 10 15 20 25 30 35 40 45 50 Ex + Met Ex + SU Ex + Met + SU Proportion achieving A1C  7% † † † † * Buse JB et al. Diabetes Care. 2004;27:2628-2635. DeFronzo RA et al. Diabetes Care. 2005;28:1092-1100. Kendall DM et al. Diabetes Care. 2005;28:1083-1091. * P <0.01 vs placebo; † P <0.0001 vs placebo. Ex=exenatide; Met=metformin; SU=sulfonylurea. † Placebo 5  g BID 10  g BID
  • 14.

Editor's Notes

  1. What’s on the Horizon: Emerging Therapies This section provides information on a new class of drugs that is on the horizon for the prevention and treatment of type 2 diabetes – the incretins.