Diabetes Update

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 • The “stats” revisited • Bariatric surgery – long-term effects on DM • Newer drugs for diabetes • Technology update • A “cure” for type 1 diabetes? • 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 2050 • ADA Report: health care costs for DM increased by 40% to $245 billion between 2007 and 2012 • JAMA 2014;311(17):1778.: Increase in prevalence in youth between 2001 and 2009 of T1D (20%) and T2D (30%)

4. Diabetes prevalence in the US leveling off?

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

6. Diabetes Update • The “stats” revisited • Bariatric surgery – long-term effects on DM • Newer drugs for diabetes • Technology update • A “cure” for type 1 diabetes? • 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 • The “stats” revisited • Bariatric surgery – long-term effects on DM • Newer drugs for diabetes • Technology update • A “cure” for type 1 diabetes? • 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. Cough ~30% • No clinically meaningful changes in PFT’s (short-term) Modest A1c reduction at 12 weeks

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. PEG (20 kDa) Insulin

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 • The “stats” revisited • Bariatric surgery – long-term effects on DM • Newer drugs for diabetes • Technology update • A “cure” for type 1 diabetes? • Endo ECHO: Meeting the needs of underserved communities

40. Continuous subcutaneous insulin infusion (CSII)

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

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

43. 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