dichiara di aver ricevuto negli ultimi due anni compensio finanziamenti dalle seguenti Aziende Farmaceuticheeo Diagnostiche
Dichiara altresigrave il proprio impegno ad astenersi nellrsquoambito dellrsquoevento dal nominare in qualsivoglia modo o forma aziende farmaceutiche eo denominazione commerciale e di non fare pubblicitagrave di qualsiasi tipo relativamente a specifici prodotti di interesse sanitario (farmaci strumenti dispositivi medico-chirurgici ecc)
Effect of Glucose-Lowering Drugs on 3-Point MACE in T2DM Patients
Study Year Glucose-loweringdrug HR 95 CI P-value
PROACTIVE 2005 Pioglitazone 084 072 - 098 002
ORIGIN 2012 Insulin glargine 102 094 - 111 NS
DEVOTE 2017 Insulin degludec 091 078 - 106 NS
SAVOR 2013 Saxagliptin 100 089 - 112 NS
EXAMINE 2013 Alogliptin 096 080 - 115 NS
TECOS 2015 Sitagliptin 098 089 - 108 NS
ELIXA 2015 Lixisenatide 102 089 - 117 NS
EMPA-REG 2015 Empagliflozin 086 074 - 099 0038
06 1 12CV mortality non-fatal MI non-fatal stroke Favors study drug Favors placebo
Effect of Glucose-Lowering Drugs on 3-Point MACE in T2DM Patients
Study Year Glucose-loweringdrug HR 95 CI P-value
PROACTIVE 2005 Pioglitazone 084 072 - 098 002
ORIGIN 2012 Insulin glargine 102 094 - 111 NS
DEVOTE 2017 Insulin degludec 091 078 - 106 NS
SAVOR 2013 Saxagliptin 100 089 - 112 NS
EXAMINE 2013 Alogliptin 096 080 - 115 NS
TECOS 2015 Sitagliptin 098 089 - 108 NS
ELIXA 2015 Lixisenatide 102 089 - 117 NS
EMPA-REG 2015 Empagliflozin 086 074 - 099 0038
LEADER 2016 Liraglutide 087 078 - 097 001
SUSTAIN-6 2016 Semaglutide 074 058 - 095 002
CANVAS 2017 Canagliflozin 086 075 - 097
06 1 12CV mortality non-fatal MI non-fatal stroke Favors study drug Favors placebo
Effect of GLP-1 RAs on CVD outcome
Bethel MA et al Lancet 2018
Effect of GLP-1 RAs on CVD outcome
Bethel MA et al Lancet 2018
Quali meccanismi
Age (yrs)
LDL-cholesterol mmoll)Systolic BP (mmHg)
UKPS 23 Risk Factors for CHD
Turner RC et al BMJ 1999316823-828
HbA1c ()
Estim
ated
HREs
timat
edHR
Estim
ated
HREs
timat
edHR
Chart1
Valore Y 1
1
16
185
Foglio1
Chart1
Valore Y 1
1
15
155
Foglio1
Chart1
Valore Y 1
1
18
19
24
Foglio1
Chart1
Valore Y 1
1
15
23
Foglio1
Adjusted Hazard Ratios for Outcomes According to Age Category and Number of Risk-Factor Variables outside Target Ranges (HbA1c LDL Album BP smoke)
Rawshani A et al N Engl J Med 2018379633-644
The Potential Mechanisms of Cardiovascular Benefits of Glucagon-like Peptide-1 Receptor Agonists
PotentialCardiovasculareffects of GLP-
1 receptoragonists
Glucose
Body weightVisceral fat
LDL CholesterolTriglycerides
AlbuminuriaGFR
Cardiac function
Cardiac Ischemia
Atherosclerosis
Blood Pressure
METABOLIC CARDIOVASCULAR
Relative Importance of Risk Factors for Predicting Death from Any Cause Acute Myocardial Infarction Stroke and Hospitalization for Heart Failure amongPatients with Type 2 Diabetes with or without Preexisting Conditions
Rawshani A et al N Engl J Med 2018379633-644
Association between Levels of Glycated Hemoglobin Systolic Blood Pressure and LDL Cholesterol and Death from Any Cause Acute Myocardial Infarction Stroke and Heart Failure in Patients with Type 2 Diabetes
Rawshani A et al N Engl J Med 2018379633-644
Quale riduzione del rischio cardiovascolare egrave stata ottenuta con il trattamento intensivo della glicemia
1 gt302 gt503 lt104 2
Residual vascular risk for macrovascolar complications in type 2 diabetic patients as reported in randomized controlled trials thatcompared more intensive glucose control vs less intensive glucosecontrol
Turnbull FM et al Diabetologia 2009Giugliano D et al Endocrine 2018
Leader Estimated mean values from randomization to end of trial for glycated hemoglobin
Glycated Hemoglobin and Body Weight in SUSTAIN 6
Marso SP et al N Engl J Med 2016
GLP-1 receptor agonists glucose control
Magnitude of cardioprotection and HbA1c loweringwith GLP-1 receptor agonists
Taylor SI GLP-1 receptor agonists differentiation within the class Lancet 2018
prim
aryo
utco
me
card
iova
scul
arde
ath
stro
ke
myo
card
ialin
farc
tion
Harmony Outcomes HbA1c and body weight
HbA1c Body weight
Magnitude of cardioprotection and HbA1c loweringwith GLP-1 receptor agonists
Taylor SI GLP-1 receptor agonists differentiation within the class Lancet 2018
GLP-1 targets multiple organs to improve glucosecontrol in T2DM
The Potential Mechanisms of Cardiovascular Benefits of Glucagon-like Peptide-1 Receptor Agonists
PotentialCardiovasculareffects of GLP-
1 receptoragonists
Glucose
Body weightVisceral fat
LDL CholesterolTriglycerides
AlbuminuriaGFR
Cardiac function
Cardiac Ischemia
Atherosclerosis
Blood Pressure
METABOLIC CARDIOVASCULAR
Quali sono gli effetti degli analoghi del GLP-1 sullrsquoassetto lipidico
1 Modesta riduzione di colesterolo e trigliceridi2 Riduzione significativa del colesterolo3 Riduzione significativa dei trigliceridi4 Riduzione HDL
GLP-1 receptor agonists impact on blood lipids
bull Network meta analysis of 35 trials with Liraglutide Exenatide Taspoglutide
bull Effectsbull HDL = -232 to -502 mgdl (NS)
bull LDL = -309 to -618 mgdl (NS)
bull TC = -618 to -1044 mgdl (NS)
bull TG = -2657 to -4340 mgdl (NS)
Clinical TherapeuticsVolume 37 Number 1 2015
GLP-1 receptor agonists
The Potential Mechanisms of Cardiovascular Benefits of Glucagon-like Peptide-1 Receptor Agonists
PotentialCardiovasculareffects of GLP-
1 receptoragonists
Glucose
Body weightVisceral fat
LDL CholesterolTriglycerides
AlbuminuriaGFR
Cardiac function
Cardiac Ischemia
Atherosclerosis
Blood Pressure
METABOLIC CARDIOVASCULAR
Anti-Atherosclerotic potential of GLP-1 action
GLP-1RndashDependent Intracellular Signal Pathways in the Cardiomyocyte
Potential Role of Epicardial Adipose Tissue in the Heart
Epicardial Adipose Tissue Mediates the Effect of Chronic SystemicInflammatory Disorders to Cause Coronary Atherosclerosis AtrialArrhythmias and Heart Failure With Preserved Ejection Fraction
Packer M JACC 2018
GLP-1
Metabolic pathways associated to GLP-1R and GLP-2R levels in EAT from CAD patients
Dozio E Int J Cardiol 2019
Epicardial fat thickness (yellow filling between the white arrows) before (on the left) and after 3 months of liraglutide combinedwith metformin treatment (on the right) in the same patient
Iacobellis G Obesity 2017
The Potential Mechanisms of Cardiovascular Benefits of Glucagon-like Peptide-1 Receptor Agonists
PotentialCardiovasculareffects of GLP-
1 receptoragonists
Glucose
Body weightVisceral fat
LDL CholesterolTriglycerides
AlbuminuriaGFR
Cardiac function
Cardiac Ischemia
Atherosclerosis
Blood Pressure
METABOLIC CARDIOVASCULAR
Quali sono gli effetti degli analoghi del GLP-1 sulla pressione arteriosa sistolica
1 Nessun effetto2 Riduzione di 3-4 mmHg3 Riduzione 7-8 mmHg4 Aumento di 1-2 mmHg
SUSTAIN-6 - Systolic Blood Pressure
0
Overall mean at baseline 1356 mmHg
104
ETD ndash259[ndash409ndash108]
ETD ndash127[ndash277023]
Marso SP et al N Engl J Med 20163751834-1844
Chart1
Semaglutide 05 mg
Semaglutide 10 mg
Placebo 05 mg
Placebo 10 mg
Weeks since randomisation
SBP (mmHg)
135625215044
135625215044
135625215044
135625215044
1326220823001
1329017953498
1344270506559
1342903775883
131410363302
1316176079892
1347289487159
1339066904146
1308730118172
1308519607697
1341780477605
134308668335
1310467105777
1291579986067
134039422375
1347658354598
1320016084484
1300861377473
1345889205084
1351424027138
130942798266
1293248728172
1347036197708
1339757480962
1320146541849
129571782354
1336576572845
1335883914333
1316159691925
1300258376555
1346010989033
1346380379755
1319145802513
1301248738036
134466367825
1343443004151
1314753976121
1291635201943
1341636273397
1331073159421
132188708252
1302541033422
1334574680557
132840710589
Sheet1
Chart1
Column3
Change from baseline (mmHg)
-344
-537
-217
-278
Sheet1
Meta-analysis of Change in Systolic (top) and Diastolic Blood Pressure (mmHg) in T2DM Patients Treated with GLP1-Ra
Visboll T et al BMJ 2012344d7771 doi 101136bmjd7771
- 357 mmHg
- 138 mmHg
LEADER amp SUSTAIN 6 ndash Renal Outcomes
SUSTAIN-6 - New or Worsening Nephropathy
LEADER - Time to first renal event
Placebo
Semaglutide
HR 06495 CI (046minus088)
p=0005
Marso SP et al N Engl J Med 2016375311-22 Marso SP et al N Engl J Med 20163751834-1844
Chart1
Semaglutide
Placebo
Weeks since randomisation
Patients with an event ()
0
00609013398
01218026797
01827783801
02439783934
03051784066
06111781131
08559779816
09172157963
0978453611
10398432864
11626226135
12854019407
13468298175
14082959671
14698388535
15315358862
15932329189
16550462148
17168595107
19641124989
2025925795
2087739091
2149552387
2211365683
22731789791
23350313974
23969622589
24589324416
25209026243
2582872807
26448429897
27068921656
27691796867
28318688036
30204226564
30833147299
31462068034
32719909239
33349239162
33978569084
34607899007
35237228929
35868618177
36500007425
37136401079
37774059092
38411717104
0
00606428138
01212856277
01821131029
02430519838
03651534885
04873298561
15258291761
17092074409
18314596468
20148379113
20759640261
2137090141
22593423468
23204684617
23815945765
24430284377
25045010096
25659735815
26274461533
27503912726
28733363918
30577540245
31807771545
3242288732
33039178474
34271760533
34889233832
35506707131
36124972062
39216292751
39834557684
41071884029
42309210373
42927873673
43546536974
44165200275
44785872223
45406544171
46027216119
47889231076
4913057471
49751652061
50373135611
50996250352
51619365092
52247016075
52877590249
53508584526
54139999746
56034244459
5666565968
59193009968
59824848108
60457111156
6109022631
61727207161
Sheet1
Effects of glucagon-like peptide 1 (GLP-1) and GLP-1 receptoragonists (GLP-1RAs) on renal haemodynamics in diabetes
Effect of 3h GLP-1 infusion on Urine Fluid and Electrolyte Output in Healthy Subjects
P=00009
P=00013 P=00004
P=02595
Gutzwiller J-P et al J Clin Endocrinol Metab 2004893055ndash3061
Chart1
Serie 1
Urine Volume (ml180 min)
360
400
639
Foglio1
Chart1
Serie 1
Urine Osmolality (mOsml)
