Sara Belcastro SCDU Endocrinologia, Diabetologia e Metabolismo Università di Torino [email protected]Congresso Congiunto AMD-SID-SIEDP-ANIED-OSDI Genova 26 ottobre 2019 Sistema nervoso centrale: effetti sulle patologie cerebrovascolari e sulle malattie degenerative del sistema nervoso Terapie del diabete: certezze consolidate e nuove prospettive
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Sara BelcastroSCDU Endocrinologia, Diabetologia e Metabolismo
Congresso Congiunto AMD-SID-SIEDP-ANIED-OSDIGenova 26 ottobre 2019
Sistema nervoso centrale: effetti sulle patologie cerebrovascolari e sulle malattie degenerative del sistema nervoso
Terapie del diabete: certezze consolidate e nuove prospettive
Dr. Sara Belcastro declares to have received in the last two yearscompensation or financing from the following pharmaceutical and/or
diagnostic companies: Merck, Novartis, Boehringer, Lilly, Mundipharma, Novo Nordisk and Bruno.
Disclosure
Ischaemic heart disease is the leading cause of mortality in patients with T2D
35%
15%10%
40%
Low Wang CC et al. Circulation 2016;133:2459–502
Non-cardiovascular causes
Ischaemic heartdisease
Other heart disease(predominantly congestive)
Stroke
Despite management of modifiable risk, placebo-treated patients were still at risk of CV and renal events
aEvent rate ranges are taken from values reported for the placebo groups in the CANVAS Program, EMPA-REG OUTCOME and DECLARE-TIMI 58 CV outcome trials; bComponents of the renal composite endpoint differed slightly across trials. CANVAS: 40% reduction in eGFR, renal replacement therapy or renal death; EMPA-REG Outcome: 40% reduction in eGFR (to < 60 ml/min/1.73 m2), end stage renal disease or renal death; DECLARE-TIMI 58: Doubling of serum creatinine accompanied by eGFR of ≤ 45 ml/min/1.73 m2, initiation renal replacement therapy or renal death. CV, cardiovascular; HF, heart failure, MI, myocardial infarction. 1. Zinman B et al. N Engl J Med 2015;373:2117–28; 2. Neal B et al.N Engl J Med 2017;377:644–57; 3. Wiviott SD et al. N Engl J Med 2019;380:347–57; 4. Wanner C et al. N Engl J Med 2016;375:1801–2
CV event rates in placebo-treated patients in CV outcome trials
CV deatha
7–20patients per
1000 patient-years1-3
Non-fatal strokea
7–9patients per
1000 patient-years1-3
Non-fatal MIa
12–19patients per
1000 patient-years1-3
Hospitalizationfor HFa
9–15patients per
1000 patient-years1-3
Renal compositea,b
7–12patients per
1000 patient-years2–4
Modifiable risk factors were addressed in patients with T2D in CV outcomes trials
aAverage of placebo-group populations from CANVAS Program, DECLARE-TIMI 58, EMPA-REG OUTCOME and overall population for VERTIS CV, CV outcomes trials bAverage of placebo-group populations from CANVAS Program, EMPA-REG Outcome and overall population for DECLARE-TIMI 58 and VERTIS CV. BMI; BMI, body mass index; CV, cardiovascular, RAS, renin–angiotensin system1. Zinman B et al. N Engl J Med 2015;373:2117–28; 2. Neal B et al. N Engl J Med 2017;377:644–57; 3.
4. Cannon CP et al. Am Heart J 2018;206:11–23; 5. Raz I et al. Diabetes Obes Metab 2018;20:1102–10.Wiviott SD et al. N Engl J Med
2019;380:347–57;
Total cholesterol1,2,4,5,b Blood pressure1–4,a Obesity (BMI)1–4,a HbA1c1–4,a
CV death 1.03 (0.87–1.22) 0.79 (0.60–1.04) 1.03 (0.89–1.19)
Fatal or non-fatal MI 0.95 (0.80–1.12) 1.08 (0.88–1.33)c 0.95 (0.81–1.11)
Fatal or non-fatal stroke 1.11 (0.88–1.39) 0.91 (0.55–1.50)c 0.97 (0.79–1.19)
Hospitalization for HF 1.27a (1.07–1.51) – 1.00 (0.83–1.20)
All-cause death 1.11 (0.96–1.27) 0.88 (0.71–1.09) 1.01 (0.90–1.14)
1. Scirica BM et al. N Engl J Med 2013;369:1317–26; 2. White WB et al. N Engl J Med 2013;369:1327–35;3. Green JB et al. N Engl J Med 2015;373:232–42; 4. Son JW, Kim S. Diabetes Metab J 2015;39:373–83
HRs (95% CI) for DPP4i CV outcomes trial endpoints
1. Pfeffer MA et al. N Engl J Med 2015;373:2247–57; 2. Marso SP et al. N Engl J Med 2016;375:311–22; 3. Marso SP et al. N Engl J Med 2016;375:1834–44; 4. Holman RR et al. N Engl J Med 2017;377:1228–39; 5. Hernandez AF et al. Lancet 2018;392:1519 –29
HRs (95% CI) for GLP1RA CV outcomes trial endpoints
J. Lovshin and David Cherney Diabetes 2015
SGLT2 inhibitors and risk of stroke in patients with type 2 diabetes: A systematic review and meta-analysis
Diabetes, Obesity and Metabolism, Volume: 20, Issue: 8
Inzucchi SE Endocrinol Metab Clin N Am 2018
Proposed glucose-lowering strategy in T2DM with CVD favoring agents demostrated to improve CV outcomes
Il passaporto di un farmaco antidiabetico Ottimizzazione del compenso glico-metabolico
Riduzione di peso
No ipoglicemia
Sicurezza CV o superiorità!
Manegevolezza
Effetti extraglicemici …capacità di modificare la storia naturale della malattia
Y. Seino, D.Yabe Journal of Diabetes Investigation 2013
GLP-1 RA Neuroprotection
Adapted from: Kim DS. et al.,Cell. Transplantation, 2017, Vol 26(9) 1560-1571
Y. Seino, D.Yabe Journal of Diabetes Investigation 2013
Exenatide had positive effects onpratically defined off-medicationmotor scores in Parkinson’s disease,which were sustained beyond theperiod of exposure. Exenatiderepresents a major new avenue forinvestigation in Parkinson’s disease,and effects on everyday symptomsshould be examined in longer-termtrials.
D. Athauda et al. The Lancet Vol 390. 2017
IY Simsir et al . Diabetes & Metabolic Syndrome Review 2018
Study ongoing…
«Sapere che sappiamo quel che sappiamo, e sapere che nonsappiamo quel che non sappiamo; questa è la vera conoscenza».