1. Diabetes Update Matt Bouchonville, MD Endocrinology Division University of New Mexico ACP New Mexico Chapter Scientific Meeting November 7, 2014 mbouchonville@salud.unm.edu

2. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

3. Diabetes: Current rates and projections CDC Press Release 2010: 1 in 3 adults with DM by 2050CDC Press Release 2010: 1 in 3 adults with DM by 2050 JAMA 2014;311(17):1778.: Increase in prevalence in youth between 2001 and 2009 of T1D (20%) and T2D (30%)JAMA 2014;311(17):1778.: Increase in prevalence in youth between 2001 and 2009 of T1D (20%) and T2D (30%) ADA Report: health care costs for DM increased by 40% to $245 billion between 2007 and 2012ADA Report: health care costs for DM increased by 40% to $245 billion between 2007 and 2012

4. Diabetes prevalence in the US leveling off?

5. Lower rates of diabetes- related complications in the US

6. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

7. Surgery group >6X’s more likely to be in remission of T2D at 15 yrs

8. Remission less likely with longer duration of diabetes

9. Surgery associated with >50% reduction in microvascular complications

10. Surgery associated with 30% reduction in macrovascular complications

11. Impact of bariatric surgery on diabetes- related complications attenuated by longer duration of diabetes

12. Conclusions Compared to usual care, bariatric surgery was associated with : Higher diabetic remission rates Fewer diabetic complications Bariatric surgery may have less influence on diabetic remission and complication rates in patients with longer duration of disease

13. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

14. SGLT2- inhibitors

17. Similar A1c reduction (-0.52%) by end of study

18. Weight loss (-3.22 kg) vs gain (+1.44 kg) with SGLT2I versus SU treatment

19. Less hypoglycemia with SGLT2I vs SU treatment

20. FDA Approval March 2013 – Canagliflozin (Invokana) January 2014 – Dapagliflozin (Farxiga) August 2014 – Empagliflozin (Jardiance) Contraindications: Severe renal impairment Adverse effects: Hypotension/dehydration, genital mycotic infections

21. Inhaled insulin

22. Afrezza (Technosphere insulin) Technosphere insulin particles made up of diketopiperazine derivatives and insulin, which self-organize into a lattice array, and form particles of 2–4 µm diameter.

23. Rapid absorption of Technosphere insulin

24. Modest A1c reduction at 12 weeks Cough ~30%Cough ~30% No clinically meaningful changes in PFT’s (short-term)No clinically meaningful changes in PFT’s (short-term)

25. Affrezza: FDA Approval June 2014 Prandial insulin in T1D or T2D Baseline PFT’s required Post-market studies in progress: –Subjects with baseline lung disease –Lung cancer risk?

26. U-300 Insulin glargine (Lantus)

27. Similar reduction in A1c compared to U-100 glargine

28. Similar reduction in FPG compared to U-100 glargine

29. Similar doses of basal and mealtime insulin

30. Less nocturnal hypoglycemia with U-300 glargine

31. Similar glycemic control and dosing with U- 300 glargine insulin but less nocturnal hypoglycemia

32. Insulin peglispro (LY2605541)

33. Insulin PEG (20 kDa)

34. Insulin peglispro (LY2605541) Patent application US 12/481,111, 2009.

35. Insulin peglispro (LY2605541) Compared to insulin glargine: Less glycemic variability Less hypoglycemia No weight gain Preferential hepatic (vs peripheral action) Diabetes Care 2014;37:659-665. Diabetes Care 2014;37:2609-2615. Diabetes 2014;63:390-392.

36. Glimins

37. Imeglimin Targets mitochondria (oxidative phosphorylation blocker) = decreased hepatic gluconeogenesis Increases skeletal muscle glucose uptake Enhanced insulin secretion in response to glucose

38. A1c reduction of 0.7% compared to addition of placebo

39. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

40. Continuous subcutaneous insulin infusion (CSII)

41. CSII allows for delivery of variable rates of basal insulin infusion throughout the day Basal insulin rates

42. Does insulin pump therapy eradicate the dawn phenomenon? Diabetes 2014;63:Supplement 1 A212-A343.

44. Unpredictability of the dawn phenomenon Roughly a 50% chance of the dawn phenomenon occurring on any given night

45. No impact on frequency of the dawn phenomenon (A) but increased hypoglycemia (B) in dawn programmers vs non-programmers *, P = 0.47 compared with dawn programmers. †, P = 0.001 compared with dawn programmers

46. Conclusions The dawn phenomenon does not occur predictably in patients with type 1 diabetes CSII programming for a fixed increase in early morning insulin to counteract the dawn phenomenon was associated with: No effect on the occurrence of the dawn phenomenon Increased rates of hypoglycemia The prevailing strategy for countering the dawn phenomenon is not effective and may be hazardous to the patient

47. FDA Approves Threshold Suspend Feature

48. Mean glucose values in 1,438 threshold suspend events

49. Less nocturnal hypoglycemia (38% reduction) with threshold suspend feature

50. No increase in hemoglobin A1c

51. No difference in rare occurrence of ketosis between control group and threshold suspend users

52. Bionic Pancreas

53. 5-day outpatient study in 20 adults and 32 adolescents with T1D Bionic pancreas vs conventional insulin pump

54. Adults: average glucose 133 mg/dL (bionic) vs 159 mg/dL (pump); P<0.001Adults: average glucose 133 mg/dL (bionic) vs 159 mg/dL (pump); P<0.001 Adolescents: average glucose 138 mg/dL (bionic) vs 157 mg/dL (pump); P=0.004Adolescents: average glucose 138 mg/dL (bionic) vs 157 mg/dL (pump); P=0.004 Adults: Percent of time hypoglycemic 4.1% (bionic) vs 7.3% (pump); P=0.01Adults: Percent of time hypoglycemic 4.1% (bionic) vs 7.3% (pump); P=0.01 Adolescents: Percent of time hypoglycemic 6.1% (bionic) vs 7.6% (pump); P=0.23Adolescents: Percent of time hypoglycemic 6.1% (bionic) vs 7.6% (pump); P=0.23

55. (almost)

56. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

57. Y Y Y Type 1 diabetic patient Islet cell transplantation Immune recognition of transplanted islet cells requires immunosuppression Encapsulation of islet cells in a PFTE device shields them from immune attack (polytetrafluoroethylene)

58. Human islet cells subcutaneously implanted into rodents After 5 months: –Stable islet cell mass –Sufficient insulin secretion to ameliorate experimental diabetes

60. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

62. No difference in sustained viral response to treatment in patients treated via ECHO model vs those treated in UNM HCV clinic ECHO model is an effective way to treat HCV infection in underserved communities

63. New Mexico Counties with Endocrinologists Type 1 diabetes referrals Type 2 diabetes referrals Data derived from NM DOH, UNM Quality Dept

64. Leona M. and Harry B. Helmsley Charitable Trust 3-year pilot program 8 Endo ECHO Centers of Excellence (COE) in New Mexico Evaluation conducted by New York University

65. Adult Endocrinologist Pediatric Endocrinologist Nephrologist RN/CDE/ nutritionist RN/CDE/ nutritionist Pharmacist Behavioral Health specialist Community Health Worker Social worker Endo ECHO: Specialist Panel

66. Endo ECHO Community Partners = Endo ECHO COE’s

67. Evaluation (NYU) Utilization measures –Hospitalizations Disease-specific outcomes –HbA1c, BP, LDL Patient-specific outcomes –Patient satisfaction, medication adherence, behavioral change Provider-specific outcomes –Provider satisfaction, self-efficacy, knowledge

68. Diabetes Update 1.The “stats” revisited 2.Bariatric surgery – long-term effects on DM 3.Newer drugs for diabetes 4.Technology update 5.A “cure” for type 1 diabetes? 6.Endo ECHO: Meeting the needs of underserved communities

69. Questions?