post easd: blodsukkersenkende medikamenter hvilke er ... · post easd: blodsukkersenkende...
TRANSCRIPT
![Page 1: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/1.jpg)
Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD
Oslo Universitetssykehus
UIT – Norges Arktiske Universitet
![Page 2: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/2.jpg)
Interessekonflikter
• Har mottatt foredragshonorar fra Eli Lilly, Boehringer
Ingelheim, NovoNordisk, MSD, Sanofi, Shire.
• Mottar lønn fra Oslo Universitetssykehus
• Passes på av HELFO iht til reguleringer fra Statens
legemiddelverk
• Mottar lønn fra Diabetesforbundet
![Page 3: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/3.jpg)
«De gode gamle»
• Sulfonylurea
• Metformin
• Insulin
• Glitazoner
(Actos)
![Page 4: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/4.jpg)
Targets of hypoglycemic agents
Metformin Insulin
Sulfonylureas Glinides DPP4 inhibitors GLP-1 analogues
SGLT2 inhibitors Insulin
Glitazones Insulin
Liver Kidney
Pancreas Skeletal muscle
![Page 5: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/5.jpg)
2013 2014 2015 2016 2017 2018 2019 2020
DECLARE
Dapagliflozin
NCT01455896
ITCA650
Intarcia
CANVAS
Canagliflozin
REWIND
Dulaglutide
Canagliflozin
FDA/PMR
TAK-875
Takeda
Insulin
degludec
NovoNordisk
EXAMINE
Alogliptin
SAVOR-TIMI
Saxagliptin
TECOS
Saxagliptin
ELIXA
Lixisenatid
EMPAREG
Empagliflozine
Canagliflozin
2nd interim
EXCEL
Exenatide
CARMELINA
Linagliptin
CAROLINA
Interim
Linagliptin
CAROLINA
Linagliptin
Omparigliptin
Merck
SUSTAIN
Semaglutide
FDA requirements
Safety studies Upper
95%
CI for
CV events
<1.3 >1.8 1.3-1.8
Approvable Not approvable Approvable with
safety studies
LEADER
Liraglutide
![Page 6: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/6.jpg)
2013 2014 2015 2016 2017 2018 2019 2020
DECLARE
Dapagliflozin
NCT01455896
ITCA650
Intarcia
CANVAS
Canagliflozin
REWIND
Dulaglutide
Canagliflozin
FDA/PMR
TAK-875
Takeda
Insulin
degludec
NovoNordisk
EXAMINE
Alogliptin
SAVOR-TIMI
Saxagliptin
TECOS
Saxagliptin
ELIXA
Lixisenatid
EMPAREG
Empagliflozine
Canagliflozin
2nd interim
EXCEL
Exenatide
CARMELINA
Linagliptin
CAROLINA
Interim
Linagliptin
CAROLINA
Linagliptin
Omparigliptin
Merck
SUSTAIN
Semaglutide
2013: SAVOR-TIMI HR 1.0 [0.89-1.12]
2013: EXAMINE HR 0.96 [UL ≤1.16]
2015: TECOS HR 0.98 [0,88-1.09]
2015: ELIXA HR 1.02 [0.89-1,17]
FDA requirements, status June 2015
LEADER
Liraglutide
![Page 7: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/7.jpg)
TECOS: Glycated Hemoglobin Level.
Green JB et al. N Engl J Med 2015;373:232-242
![Page 8: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/8.jpg)
Kaplan–Meier Curves for Primary and Secondary Outcomes (Intention-to-Treat Population).
Green JB et al. N Engl J Med 2015;373:232-242
![Page 9: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/9.jpg)
2013 2014 2015 2016 2017 2018 2019 2020
DECLARE
Dapagliflozin
NCT01455896
ITCA650
Intarcia
CANVAS
Canagliflozin ?
REWIND
Dulaglutide
Canagliflozin
FDA/PMR
TAK-875
Takeda
Insulin
degludec
NovoNordisk
EXAMINE
Alogliptin
SAVOR-TIMI
Saxagliptin
TECOS
Saxagliptin
ELIXA
Lixisenatid
EMPAREG
Empagliflozine
Canagliflozin
2nd interim
EXCEL
Exenatide
CARMELINA
Linagliptin
CAROLINA
Interim
Linagliptin
CAROLINA
Linagliptin
Omparigliptin
Merck
SUSTAIN
Semaglutide
LEADER
Liraglutide
![Page 10: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/10.jpg)
2013 2014 2015 2016 2017 2018 2019 2020
DECLARE
Dapagliflozin
NCT01455896
ITCA650
Intarcia
CANVAS
Canagliflozin Sulfonylurea
REWIND
Dulaglutide
Canagliflozin
FDA/PMR
TAK-875
Takeda
Insulin
degludec
NovoNordisk
EXAMINE
Alogliptin
SAVOR-TIMI
Saxagliptin
TECOS
Saxagliptin
ELIXA
Lixisenatid
EMPAREG
Empagliflozine
Canagliflozin
2nd interim
EXCEL
Exenatide
CARMELINA
Linagliptin
CAROLINA
Interim
Linagliptin
CAROLINA
Linagliptin
Omparigliptin
Merck
SUSTAIN
Semaglutide
LEADER
Liraglutide
![Page 11: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/11.jpg)
2013 2014 2015 2016 2017 2018 2019 2020
DECLARE
Dapagliflozin
NCT01455896
ITCA650
Intarcia
CANVAS
Canagliflozin Sulfonylurea
REWIND
Dulaglutide
Canagliflozin
FDA/PMR
TAK-875
Takeda
Insulin
degludec
NovoNordisk
EXAMINE
Alogliptin
SAVOR-TIMI
Saxagliptin
TECOS
Saxagliptin
ELIXA
Lixisenatid
EMPAREG
Empagliflozine
Canagliflozin
2nd interim
EXCEL
Exenatide
CARMELINA
Linagliptin
CAROLINA
Interim
Linagliptin
CAROLINA
Linagliptin
Omparigliptin
Merck
SUSTAIN
Semaglutide
LEADER
Liragluide
![Page 12: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/12.jpg)
Le médaille d’or
Metformin
•Mekanisme uavhengig av beta-cellen
•Gir ikke hypoglykemi i monoterapi
•UKPDS 34 (Lancet 1998;352:854-65)
– Overvektige personer med T2DM
– n=342 vs. 951 personer med SU/ insulin
– Sekundæranalyse: CV
– ACEi eller statiner var ikke brukt
![Page 13: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/13.jpg)
PLoS Medicine 2012;9: e1001204
![Page 14: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/14.jpg)
Boussageon R, et al. PLoS Medicine 2012;9: e1001204
Gir ikke hypoglykemi
eller vektøkning.
Døgnpris 1-3 NOK
Total
mortality
CV
mortality
![Page 15: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/15.jpg)
Diabetes Care 2008;31:1672-8
![Page 16: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/16.jpg)
Rao et al., Diabetes Care 2008;31:1672-8
![Page 17: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/17.jpg)
EASD 2015
• Nunes AP, et al. USA. Interim results on the relationship between mild-
moderate and severe hyperglycaemia and cardiovascular disease in a cohort of
sulfonylurea users (n=82.321)
• Baxter CA, et al. Canada. Increased risk of cardiovascular-related events
associated with sulfonylureas compared toother antihyperglycemic drugs: a
Bayesian meta-analysis of survival data (91 RCTs with 36.573 patients, 26
observational studies with 1.553.856 patients)
• Eriksson JW, et al. Sweden. Second-line treatment with sulfonylurea compared
to DPP4 inhibitors is associated with risk of cardiovascular disease, all cause
mortality and severe hypoglycaemia (n=68.351)
• Berg B, et al. Germany. Treatment characteristics and outcomes associated
with sulphonylurea versus metformin therapy in incident type 2 diabetes
mellitus patients, results of the German CREST study (n=35.661)
![Page 18: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/18.jpg)
![Page 19: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/19.jpg)
Roumie L, et al. Ann Intern Med 2012; 157: 601-10
![Page 20: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/20.jpg)
Nissen SE, Ann Intern Med 2012; 157: 671-2
”How might sulfonylureas increase adverse CV outcomes?.......
Regardless of mechanisms, this scientific question demands
a definite answer. In the asbsence of an industry-sponsored
study, public health authorities should conduct such a clinical
trial. With more than two thirds of diabetic patients dying of
CV causes and millions of patients currently receiving
sulfonylureas, this question must be resolved with high-quality
evidence. Continued darkness is not an acceptable option.”
![Page 21: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/21.jpg)
Bare konger, redaktører og folk
med bendelorm har rett til å bruke
det redaksjonelle vi *
Mark Twain (1874-1891)
*…og kanskje Helsedirektoratet (?)
![Page 22: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/22.jpg)
Levevaner
SU DPP4i
Metformin
GLP-1 Glitazoner Insulin SGLT2i
Trond Jenssen 24.09.2015
![Page 23: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/23.jpg)
Adverse Clinical Outcomes among Patients with Severe Hypoglycemia
Zoungas S et al. N Engl J Med 2010;363:1410-1418
![Page 24: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/24.jpg)
Å leve med type 2-diabetes n=2725
Andel påvirket av hypoglykemi i daglige aktiviteter (%)
Sjøholm Å, et al. 2012
17 12 9 25 22 27 26 26 11
38 27 27 56 40 49 52 50 26
![Page 25: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/25.jpg)
46 studier, n=532.432
Hypoglykemi hos 51%
(6% alvorlig hypoglykemi)
20 pr. pasientår med insulin
2 pr. pasientår med tabletter
![Page 26: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/26.jpg)
![Page 27: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/27.jpg)
![Page 28: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/28.jpg)
The Risk of Severe Hypoglycaemia: Post-hoc
Epidemiological Analysis of the ACCORD Study
Diabetes duration (years)
BMI (kg/m2)
Serum creatinine (mol/l)
*History of peripheral neuropathy (yes vs. no); **per 1 year increase
P=0.03
P=0.01
P<0.0001
P<0.0001
P<0.0001
P<0.03
P<0.0001
Miller ME et al . BMJ 2010;340: b5444
A B C C D
![Page 29: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/29.jpg)
Levevaner
SU* DPP4i
Metformin
GLP-1 Pioglitazon Insulin SGLT2i
Trond Jenssen 24.09.2015
Hvilke medikamenter er «sikre»?
*Avvent resultater fra Carolina-studien
![Page 30: Post EASD: Blodsukkersenkende medikamenter hvilke er ... · Post EASD: Blodsukkersenkende medikamenter – hvilke er trygge å bruke i dag? Trond Jenssen MD, PhD Oslo Universitetssykehus](https://reader031.vdocuments.pub/reader031/viewer/2022022804/5c932db209d3f206488c21ef/html5/thumbnails/30.jpg)