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Managing T2D in 2017

Managing T2D in 2017. Matt Bouchonville Endocrinology Division Family Medicine Resident School February 8, 2017. Objectives. ADA 2017 guidelines – anything we need to know this year? Emerging cardiovascular benefits of newer diabetes therapies. What hasn’t changed? The “ABCs”.

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Managing T2D in 2017

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  1. Managing T2D in 2017 Matt Bouchonville Endocrinology Division Family Medicine Resident School February 8, 2017

  2. Objectives • ADA 2017 guidelines – anything we need to know this year? • Emerging cardiovascular benefits of newer diabetes therapies

  3. What hasn’t changed? The “ABCs” • A1c <7% for most patients • Fasting & premeal BG targets (2015): • 80-130 mg/dL • Blood pressure targets (2015): • 140/90 mmHg for most patients • Cholesterol (statin) therapy (2015): • Old = LDL target driven (<100 or <70 mg/dL) • New = CVD risk driven

  4. ADA 2017: Statin treatment

  5. (IMPROVE-IT) Modest reduction in composite CV outcome with addition of ezetimibe to statin post-ACS

  6. What are some of the changes to ADA recommendations?

  7. 1. 42 year-old woman with type 2 diabetes returns to clinic with BP 148/92 mmHg. She has no microvascular complications. Which of the following medications should be started for hypertension? • Lisinopril • Losartan • Hydrochlorothiazide • Amlodipine • Any of the above are appropriate

  8. Answer E. Any of the above

  9. Each of these classes found to reduce CV events in hypertensive patients with diabetes in two systematic reviews *Note: ACE or ARB is still favored in the setting of albuminuria JAMA 2015;313:603-615. BMJ 2016;352:i438.

  10. 2. A 52 year-old man has long-standing type 2 diabetes complicated by neuropathy. A1c is 7.1% on metformin. Metformin use is associated with deficiency of which of the following vitamins? • Vitamin A • Vitamin B-12 • Vitamin C • Vitamin D • Vitamin E

  11. Answer B. Vitamin B-12

  12. Long term metformin use was associated with an increased risk of B12 deficiency (<203 pg/mL) in the Diabetes Prevention Program Outcomes Study (DPPOS) J Clin Endocrinol Metab 2016;101(4):1754-61.

  13. QUESTION

  14. 3. A 34 year-old obese woman with family history of type 2 diabetes and negative GAD antibodies presents with new diagnosis of type 2 diabetes. A1c is 10.1% and fasting BG is 312 mg/dL. In addition to lifestyle management, which of the following treatments might be most appropriate for this patient? • None (lifestyle management alone) • Metformin • Metformin plus glipizide • Metformin plus basal insulin • Armour thyroid

  15. Answer D. Metformin plus basal insulin

  16. Algorithm has been revised!

  17. What if baseline A1c >10% or BG >300 mg/dL or patient is markedly symptomatic or if suboptimal control on max non-insulin therapy?

  18. Insulin glargine + TID lispro vs Insulin glargine + exenatide

  19. Exenatide therapy: • Less nocturnal hypoglycemia • Higher patient-satisfaction • Increased risk GI side effects HbA1c Weight

  20. What if there are contraindications to GLP-1 agonist therapy (i.e. gastroparesis, history of pancreatitis, financial barriers)?

  21. Adding rapid-acting insulin to basal insulin: One meal? Two? All meals? Endocr Pract 2011;17(3):395.

  22. Objectives • ADA 2017 guidelines – anything we need to know this year? • Emerging cardiovascular benefits of newer diabetes therapies

  23. SGLT2-inhibitors

  24. 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, hyperkalemia, DKA?, fractures?

  25. 1,450 T2D patients uncontrolled (mean A1c 7.8%) on metformin • Randomized to canagliflozin 100 mg, 300 mg, or glimepiride (titrated up to 6-8 mg/day) • 52 week core period plus 52 week extension Diabetes Care 2015;38:355-364.

  26. Similar A1c reduction (slightly better in CANA 300 mg) Diabetes Care 2015;38:355-364.

  27. Significant weight loss in CANA groups Sulfonylurea SGLT2I Diabetes Care 2015;38:355-364.

  28. Modest BP lowering effect of CANA Sulfonylurea SGLT2I Diabetes Care 2015;38:355-364.

  29. Less hypoglycemia in CANA groups % Hypoglycemia Diabetes Care 2015;38:355-364.

  30. SGLT2 inhibitor-associated AEs *including dry mouth, nocturia, urgency, polyuria, thirst Diabetes Care 2015;38:355-364.

  31. Is there any cardiovascular benefit of SGLT2 inhibitor therapy? EMPA-REG Trial

  32. 7,020 T2D patients with CVD • Mean age 63 yrs, A1c ~8%, BMI ~31 • Randomized to empagliflozin 10mg, 25mg, or placebo (double blind) Primary outcome: Composite of death from cardiovascular causes, nonfatal MI, nonfatal CVA N Engl J Med 2015;373:2117-2128.

  33. Modest A1c reduction with EMPA Placebo Empagliflozin 29% of placebo, 23% of EMPA discontinued tx prematurely N Engl J Med 2015;373:2117-2128.

  34. Modest reduction (14%) in primary outcome Placebo Empagliflozin N Engl J Med 2015;373:2117-2128.

  35. CV Death reduced by 38% Placebo Empagliflozin N Engl J Med 2015;373:2117-2128.

  36. HF Hospitalization reduced by 35% Placebo Empagliflozin N Engl J Med 2015;373:2117-2128.

  37. What is the explanation for the reduction in CV death? No difference in rates of MI or CVA Only 10% with HF at baseline Diuretics (excepting aldosterone antagonists) have not been shown to reduce mortality

  38. What is the explanation for the reduction in CV death? Related to modest BP reduction (~4 mmHg)? Related to modest weight loss (~2 kg)? Unidentified mechanism?

  39. DKA occurred in ≤ 0.1% of subjects in all groups • Warning: SGLT2 inhibitors may result in diabetic ketoacidosis • Based on 20 reports • Several other cases reported since May 2015

  40. Warning: Canagliflozin may increase fracture risk • Canagliflozin associated with reduced total hip BMD, increased fracture rate • Recent meta-analysis 38 RCTs (38K pts) reported no increased fracture rate Sept 2015 J Clin Endocrinol Metab 2016;101(1):157 and 44. Diabetes Obes Metab 2016;PMID 27407013.

  41. GLP-1 agonists

  42. GLP-1 Modulates Numerous Functions GLP-1: Secreted upon the ingestion of food Promotes satiety and reduces appetite Alpha cells:  Postprandialglucagon secretion Beta cells:Enhances glucose-dependent insulin secretion Liver: Glucagon reduces hepatic glucose output Stomach: Helps regulate gastric emptying Data from Flint A, et al. J Clin Invest. 1998;101:515-520; Data fromLarsson H, et al. Acta PhysiolScand. 1997;160:413-422Data fromNauck MA, et al. Diabetologia. 1996;39:1546-1553; Data from Drucker DJ. Diabetes. 1998;47:159-169

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