Endocrinologist Sweetgrass Endocrinology

Sanders, Cummings Ask Justice Department to Investigate Insulin Prices The Department of Justice and the FTC are asked to investigate whether Lilly, Novo Nordisk, and Sanofi colluded to raise prices. Recent Reports from Washington post and bloomberg, the lawmakers said there was evidence the drugmakers raised insulin prices for popular brands in unison.

FDA APPROVES MINIMED 670G SYSTEM WORLD S FIRST HYBRID CLOSED LOOP SYSTEM

Generic: Degludec Brand name: Tresiba Duration: 42 hours Maximum single injection: 160 units Insulin in 1 pen: u100-300 units u200-600 units

Empagliflozin is SGLT-2 inhibitor Primary Endpoint: MACE Death from cardiovascular causes Nonfatal myocardial infarction Nonfatal stroke Secondary Endpoint Hospitalization + Primary Endpoint

Perseghin and Solini Cardiovasc Diabetol (2016) 15:85 DOI 10.1186/s12933-016-0403-8

EMPA-REG OUTCOME: Cardiovascular death HR 0.62 (95% CI 0.49, 0.77) p=0.0001 38% N=7020 Cumulative incidence function. HR, hazard ratio Zinman B et al. N Engl J Med 2015, published on-line, 9-1-15, DOI:10.1056/NEJMoa1504720 9

EMPA-REG OUTCOME: Hospitalization for heart failure HR 0.65 (95% CI 0.50, 0.85) p=0.0017 35% N=7020 Cumulative incidence function. HR, hazard ratio Zinman B et al. N Engl J Med 2015, published on-line, 9-1-15, DOI:10.1056/NEJMoa1504720 10

HR 0.66 (95% CI 0.55, 0.79) P<0.0001 34% Cumulative incidence function. CV, cardiovascular; HR, hazard ratio; CI, confidence interval. Zinman B et al. N Engl J Med 2015, published on-line, 9-1-15, DOI:10.1056/NEJMoa1504720 11

25 20 15 20.1 16.2 10 5 7.1 4.5 0 Patients without heart failure Patients with heart failure Taken from Empa Reg Outcome Dr.Inzucchi PPT Deck

Taken from http://www.nephjc.com/news/2016/6/23/empa-reg-renal-results Wanner, Christoph, et al. "Empagliflozin and progression of kidney disease in type 2

Taken from http://www.nephjc.com/news/2016/6/23/empa-reg-renal-results Wanner, Christoph, et al. "Empagliflozin and progression of kidney disease in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 323-334.

Canagliflozin : 12 episodes in DKA among 17000 patient. Less than 1 in 1000 (300 mg) and 1 in 1000 around (100 mg). T2DM DKA: 0.5 per 1000 patient years 6 out of 12 GAD 65, 10/12 were on insulin. 2/12 were not on insulin out 1 T2DM and 1 had subcutaneous abscess and acute pancreatitis. 8/12 were enrolled in CANVAS which included significant comorbid conditions.

Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Eng J Med 2016; 374: 1321-31.

9,340 patients with type 2 diabetes. The primary composite outcome in the time-toevent analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (MACE) 81% patient have prior CVD Rest were high risk of CVD Long Term therapy duration of DM 12 yrs with meal HbA1C 8.7. Pancreatitis was lower in Liraglutide group nonsignificantly. Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

Adapted from: Marso SP et al., NEJM 2016 Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322. LEADER trial: Death from Cardiovascular Causes Patients with an event (%) 20 15 10 5 0 Hazard ratio, 0.78 (95% CI, 0.66 0.93) P=0.007 0 6 12 18 24 30 36 42 48 54 Months since randomization Placebo Liraglutide Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial

LEADER trial: Primary Outcome First occurrence of CV death, nonfatal myocardial infarction, or nonfatal stroke in the time-toevent analysis in patients with type 2 diabetes and high CV risk. Patients with an event (%) 20 15 10 5 0 Hazard ratio, 0.87 (95% CI, 0.78 0.97) P<0.001 for noninferiority P=0.01 for superiority Placebo Liraglutide 0 6 12 18 24 30 36 42 48 54 Months since randomization Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial Adapted from: Marso SP et al., NEJM 2016 Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322.

2735 patients with 83% CAD,CKD or both Primary outcome MACE 2 yrs Retinopathy increased Nephropathy decreased Low incidence of pancreatitis same as placebo. Marso, Steven P., et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." New England Journal of Medicine (2016).

Marso, Steven P., et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." New England Journal of Medicine (2016).

Marso, Steven P., et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." New England Journal of Medicine (2016). Marso, Steven P., et al. "Liraglutide and cardiovascular outcomes in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 311-322. Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. N Eng J Med 2016; 374: 1321-31. Perseghin and Solini Cardiovasc Diabetol (2016) 15:85 DOI 10.1186/s12933-016-0403-8 Wanner, Christoph, et al. "Empagliflozin and progression of kidney disease in type 2 diabetes." New England Journal of Medicine 375.4 (2016): 323-334.

http://www.nephjc.com/news/2016/6/23/emp a-reg-renal-results