L’evoluzione della terapia del diabete tipo 2 - Marchesini Giulio - L... · L’evoluzione della...
Transcript of L’evoluzione della terapia del diabete tipo 2 - Marchesini Giulio - L... · L’evoluzione della...
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L’evoluzione della terapia del diabete tipo 2
Giulio Marchesini“Alma Mater” Università di BolognaDipartimento di Scienze Mediche e
Chirurgiche
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DisclosuresGiulio Marchesini• Advisory Board: Lilly, Gilead• Honoraria: Sanofi, Merck Sharp & Dome, Novartis• Clinical Studies: Boehringer Ingelheim, Janssen Cilag,
Sanofi, Lilly, Novo Nordisk, Gilead, GENFIT, Glaxo
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Draft della presentazione• Stato attuale del trattamento• Momenti topici nel cambiamento
– Proactive– NHI regulatory action– GLP-1RAs – DPP-4Is– Grandi trial (Advance – Accord – VADT)– SGLT-2Is– Degludec– EMPA-REG Outcome– TECOS – EXAMINE – SAVOR-TIMI– Biosimilare di Glargine– Glargine 300– GLP-1RAs settimanali– GLP-1RAs+Insulina basale
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Trend di prevalenza e spesa negli anni
2017
0
50
100
150
200
250
300
350
0
1
2
3
4
5
619
97
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
Spes
a m
edia
per
trat
tato
(€)
Prev
alen
za
Anno
Prevalenza pop F Prevalenza pop M Spesa media trattato F Spesa media trattato M
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ARNO 2015Costi diretti del diabete
2015
2898
1638
Chart1
Diabetes All casesDiabetes All casesDiabetes All casesDiabetes All casesDiabetes All cases
NO DiabetesNO DiabetesNO DiabetesNO DiabetesNO Diabetes
Non-diabetes drugs
Diabetes drugs
Hospital admission
Monitoring systems
Services
592
191
1396
119
600
356
842
440
Foglio1
Diabetes All casesNO Diabetes
Non-diabetes drugs592356
Diabetes drugs191
Hospital admission1396842
Monitoring systems119
Services600440
Categoria 44.5
Per ridimensionare l'intervallo di dati del grafico, trascinare l'angolo inferiore destro dell'intervallo.
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Andamento della terapia con anti-iperglicemici non-insulinici
%
Anno
-1.6%Anti-iperglicemici non-insulinici
Miccoli R. – adattato da Rapporto ARNO-Diabete 2017
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Andamento della terapia con anti-iperglicemici non-insulinici impiegati non in combinazione precostituita
Anno
% +500%Metformina
Sulfonilureee -46%
Incretine +500%
Miccoli R. – adattato da Rapporto ARNO-Diabete 2017
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Andamento nella frequenza d’uso dei sulfoniluree+glinidi in relazione alle classi di età
%
Classi di età (anni)
-87% -75%
-66%
-60%
-52%
-46%
Miccoli R. – adattato da Rapporto ARNO-Diabete 2017
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Trattamento insulinico in relazione all’età
Fra tutti i pazienti in terapia insulinica (26%), il 64% ha più di 65 anni. Solo il 6% ha meno di 35 anni.
6%
64%
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Impiego dell’insulina umana (DNA-r) e degli analoghi dell’insulina nel corso degli anni
%
Anno
28%
22%
Miccoli R. – adattato da Rapporto ARNO-Diabete 2017
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La scala dei farmaci del diabete
Cahn, Lancet Diabetes Endocrinol 2015
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La scala dei farmaci del diabete
Cahn, Lancet Diabetes Endocrinol 2015
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Superiority
Noninferiority
Noninferiority
Inferiority
Underpowered
Approvable;CV safety study post approvalmay not be required
Approvable; need for CV safety study
Not approvable
NoninferiorityBoundary
HR 1.3
NoninferiorityBoundary
HR 1.8
0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0 2.2Hazard ratio
BEST
Statistical Criteria for Approval1
Five hypothetical examples of possible HRs, and regulatory consequences
Hirshberg B et al. Diabetes Care. 2011:34 (Suppl 2);S101–S106.
FDA = Food and Drug Administration; HR = hazard ratio; CV = cardiovascular.
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SAVOR-TIMI (Saxagliptin) 1
EXAMINE (Alogliptin) 2
TECOS (Sitagliptin)3
Recruitment Period
Sept 2010 Jan 2012 2009 2012 Dec 2008 July 2012
Primary Endpoint
Composite of CV death, nonfatal MI, nonfatal stroke
Composite ofCV death, nonfatal myocardial infarction, and nonfatal stroke
Composite of CV death, nonfatal MI, nonfatal stroke, or unstable angina requiring hospitalization
Analysis Population/ # of events
ITT for both NI and superiority
Powered for 1040 events
NI, then superiorityType of analysis not mentioned in design paper
Powered for 650 events
PP for NI; ITT for superiority
Powered for 1300 events
Completion Date
Q3 2013 Q4 2013 Q4 2014
Comparison of CV Outcome Study Design
1-Scirica BM et al, Am Heart J 2011; 2-White W. et al Am Heart J 2011; 3-Clinicaltrials.gov accessed, 2013
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ACCORD, ADVANCE & VADT –Effect of intensive treatment on glycaemic control
ACCORD1
VADT3 ADVANCE2
ACCORD1 ADVANCE2 VADT3
A1c at entry (%) 8.1 7.2 9.4
Target A1c
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Time since diagnosis (years) Del Prato, Diabetologia 2009
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Analisi di risultato
Factors associated with the probability to achieve hemoglobin A1c 80%.
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R
R
R
Durata media del follow-up
EXAMINE = Examination of Cardiovascular Outcomes: Alogliptin vs Standard of Care in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome;SAVOR-TIMI= Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus Trial-Thrombolysis in Myocardial Infarction; TECOS = Trial Evaluating Cardiovascular Outcomes With Sitagliptin. CV = cardiovascular; MI = myocardial infarction; UA = unstable angina.White WB et al. N Engl J Med. 2013;369:1327–1335. Scirica BM et al. N Engl J Med 2013;369:1317–1326. Green JB et al. Am Heart J. 2013;166:983–989.e7. 4. Bethel MA et al. Diabetes Obes Metab. 2015; 10.1111/dom.12441.
EXAMINE, SAVOR-TIMI e TECOS
SAVOR-TIMI2
TECOS3,4
EXAMINE1
6.5–8.0Morte CV ,
IM non fatale, oIctus non fatale o UA req.
ospedalizzazione
Randomizzazione Anno 3Anno 2Anno 1
Morte CV ,IM non fatale, oIctus non fatale
Morte CV ,IM non fatale, oIctus non fatale
Sitagliptin
Saxagliptin
Alogliptin
Placebo
Placebo
Placebo
6.5–12.0
6.5–11.0
HbA1c% End point PrimarioDurata del trattamento
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Canaglifozin – Effects on body weight
Cefalù, ADA Chicago 2013
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DURATION trials Change in body weight from baseline
†Exenatide QW is not indicated for the management of obesity, and weight change was a secondary endpoint in clinical trials.
Data from 24–30 Weeks. *P
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Composite endpoint Hba1c
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Zinman, N Engl J Med 2015
Death from CV causes, nonfatal MI, or nonfatal stroke
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Zinman, N Engl J Med 2015
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Zinman, N Engl J Med 2015
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Zinman, N Engl J Med 2015
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Wanner, N Engl J Med 2016
In the recent EMPA-REG OUTCOME trial, the primary goal was to assess cardiovascular outcomes. Here we report the results of a prespecified secondary objective of that trial, which was to examine the effects of empagliflozin on micro-vascular outcomes and, in particular, progression of kidney disease in patients with T2DM at high risk for cardiovascular events.
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Wanner, N Engl J Med 2016
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Neal, N Engl J Med 2017
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Mahaffey, Circulation (in press)
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Mahaffey, Circulation (in press)
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Marso, N Engl J Med 2016
Primary composite outcome: first occurrence of death from cardiovascular causes, nonfatal (including silent) myocardial infarction, or nonfatal stroke.
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Marso, N Engl J Med 2016
Exploratory outcomes: composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina pectoris or heart failure), death from any cause, a composite renal and retinal microvascular outcome
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Marso, N Engl J Med 2016
Exploratory outcomes: composite cardiovascular outcome (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina pectoris or heart failure), death from any cause, a composite renal and retinal microvascular outcome
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DURATION trialsHbA1c reductions of −1.3% to −1.9%
Exenatide BID¶2N=295
30 weeks
Exenatide BID¶3N=252
24 weeks
Baseline (%)
Sitagliptin (100 mg QD) or pioglitazone (45 mg QD)¶1 N=491
26 weeksInsulin glargine#5
N=44826 weeks
Exenatide QW vs Liraglutide 1.8 mg¶4N=911
26 weeks
Sitagliptin Pioglitazoneexenatide QW LiraglutideExenatide BID Insulin glargine−1.9%†
−1.5% −1.6%‡
−0.9%
LS m
ean
chan
ge in
HbA
1c(%
)
0
−0.5
−1.0
−1.5
−2.0
−1.5%*
−1.2%
−0.9%
8.3 8.3 8.5 8.48.6 8.5 8.5 8.3 8.3
−1.5% −1.5%||−1.3%−1.3%§
8.5 8.4
Data from 24–30 Weeks. *P
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Proportion of Patients Achieving HbA1c
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Davies, JAMA 2016
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Marso, N Engl J Med 2016
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Effetto dei farmaci ipoglicemizzanti sul MACE-3 nel DM2
EXSCEL EXENATIDE HR 0.91 95 % IC 0,83-1 P < 0.001 per non inferiorita , p 0.06 per superiorita
CANVAS HR 0,86 95 % IC 0.52-0,87 p 0,001 non inf eriorita , p0.02 per superiorita
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Holman, N Engl J Med 2017
The primary composite out-come was the first occurrence of death from cardiovascular causes, nonfatal myo-cardial infarction, or nonfatal stroke.
Among patients with T2DM w/woprevious CVD, the incidence of major adverse CV events did not differ significantly between patients who received exenatide and those who received placebo.
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Confirmed hypoglycaemia
SASComparisons: Estimates adjusted for multiple covariates
18% risk reduction, p=0.036
IDeg OD (n=753)IGlar OD (n=251)
Time (weeks)
Con
firm
ed h
ypog
lyca
emia
(cum
ulat
ive
even
ts p
er p
atie
nt)
Garber A et al. Lancet 2012;379:1498-507
Chart1
00
0.14285714290.1428571429
0.28571428570.2857142857
0.42857142860.4285714286
0.57142857140.5714285714
0.71428571430.7142857143
0.85714285710.8571428571
11
1.14285714291.1428571429
1.28571428571.2857142857
1.42857142861.4285714286
1.57142857141.5714285714
1.71428571431.7142857143
1.85714285711.8571428571
22
2.14285714292.1428571429
2.28571428572.2857142857
2.42857142862.4285714286
2.57142857142.5714285714
2.71428571432.7142857143
2.85714285712.8571428571
33
3.14285714293.1428571429
3.28571428573.2857142857
3.42857142863.4285714286
3.57142857143.5714285714
3.71428571433.7142857143
3.85714285713.8571428571
44
4.14285714294.1428571429
4.28571428574.2857142857
4.42857142864.4285714286
4.57142857144.5714285714
4.71428571434.7142857143
4.85714285714.8571428571
55
5.14285714295.1428571429
5.28571428575.2857142857
5.42857142865.4285714286
5.57142857145.5714285714
5.71428571435.7142857143
5.85714285715.8571428571
66
6.14285714296.1428571429
6.28571428576.2857142857
6.42857142866.4285714286
6.57142857146.5714285714
6.71428571436.7142857143
6.85714285716.8571428571
77
7.14285714297.1428571429
7.28571428577.2857142857
7.42857142867.4285714286
7.57142857147.5714285714
7.71428571437.7142857143
7.85714285717.8571428571
88
8.14285714298.1428571429
8.28571428578.2857142857
8.42857142868.4285714286
8.57142857148.5714285714
8.71428571438.7142857143
8.85714285718.8571428571
99
9.14285714299.1428571429
9.28571428579.2857142857
9.42857142869.4285714286
9.57142857149.5714285714
9.71428571439.7142857143
9.85714285719.8571428571
1010
10.142857142910.1428571429
10.285714285710.2857142857
10.428571428610.4285714286
10.571428571410.5714285714
10.714285714310.7142857143
10.857142857110.8571428571
1111
11.142857142911.1428571429
11.285714285711.2857142857
11.428571428611.4285714286
11.571428571411.5714285714
11.714285714311.7142857143
11.857142857111.8571428571
1212
12.142857142912.1428571429
12.285714285712.2857142857
12.428571428612.4285714286
12.571428571412.5714285714
12.714285714312.7142857143
12.857142857112.8571428571
1313
13.142857142913.1428571429
13.285714285713.2857142857
13.428571428613.4285714286
13.571428571413.5714285714
13.714285714313.7142857143
13.857142857113.8571428571
1414
14.142857142914.1428571429
14.285714285714.2857142857
14.428571428614.4285714286
14.571428571414.5714285714
14.714285714314.7142857143
14.857142857114.8571428571
1515
15.142857142915.1428571429
15.285714285715.2857142857
15.428571428615.4285714286
15.571428571415.5714285714
15.714285714315.7142857143
15.857142857115.8571428571
1616
16.142857142916.1428571429
16.285714285716.2857142857
16.428571428616.4285714286
16.571428571416.5714285714
16.714285714316.7142857143
16.857142857116.8571428571
1717
17.142857142917.1428571429
17.285714285717.2857142857
17.428571428617.4285714286
17.571428571417.5714285714
17.714285714317.7142857143
17.857142857117.8571428571
1818
18.142857142918.1428571429
18.285714285718.2857142857
18.428571428618.4285714286
18.571428571418.5714285714
18.714285714318.7142857143
18.857142857118.8571428571
1919
19.142857142919.1428571429
19.285714285719.2857142857
19.428571428619.4285714286
19.571428571419.5714285714
19.714285714319.7142857143
19.857142857119.8571428571
2020
20.142857142920.1428571429
20.285714285720.2857142857
20.428571428620.4285714286
20.571428571420.5714285714
20.714285714320.7142857143
20.857142857120.8571428571
2121
21.142857142921.1428571429
21.285714285721.2857142857
21.428571428621.4285714286
21.571428571421.5714285714
21.714285714321.7142857143
21.857142857121.8571428571
2222
22.142857142922.1428571429
22.285714285722.2857142857
22.428571428622.4285714286
22.571428571422.5714285714
22.714285714322.7142857143
22.857142857122.8571428571
2323
23.142857142923.1428571429
23.285714285723.2857142857
23.428571428623.4285714286
23.571428571423.5714285714
23.714285714323.7142857143
23.857142857123.8571428571
2424
24.142857142924.1428571429
24.285714285724.2857142857
24.428571428624.4285714286
24.571428571424.5714285714
24.714285714324.7142857143
24.857142857124.8571428571
2525
25.142857142925.1428571429
25.285714285725.2857142857
25.428571428625.4285714286
25.571428571425.5714285714
25.714285714325.7142857143
25.857142857125.8571428571
2626
26.142857142926.1428571429
26.285714285726.2857142857
26.428571428626.4285714286
26.571428571426.5714285714
26.714285714326.7142857143
26.857142857126.8571428571
2727
27.142857142927.1428571429
27.285714285727.2857142857
27.428571428627.4285714286
27.571428571427.5714285714
27.714285714327.7142857143
27.857142857127.8571428571
2828
28.142857142928.1428571429
28.285714285728.2857142857
28.428571428628.4285714286
28.571428571428.5714285714
28.714285714328.7142857143
28.857142857128.8571428571
2929
29.142857142929.1428571429
29.285714285729.2857142857
29.428571428629.4285714286
29.571428571429.5714285714
29.714285714329.7142857143
29.857142857129.8571428571
3030
30.142857142930.1428571429
30.285714285730.2857142857
30.428571428630.4285714286
30.571428571430.5714285714
30.714285714330.7142857143
30.857142857130.8571428571
3131
31.142857142931.1428571429
31.285714285731.2857142857
31.428571428631.4285714286
31.571428571431.5714285714
31.714285714331.7142857143
31.857142857131.8571428571
3232
32.142857142932.1428571429
32.285714285732.2857142857
32.428571428632.4285714286
32.571428571432.5714285714
32.714285714332.7142857143
32.857142857132.8571428571
3333
33.142857142933.1428571429
33.285714285733.2857142857
33.428571428633.4285714286
33.571428571433.5714285714
33.714285714333.7142857143
33.857142857133.8571428571
3434
34.142857142934.1428571429
34.285714285734.2857142857
34.428571428634.4285714286
34.571428571434.5714285714
34.714285714334.7142857143
34.857142857134.8571428571
3535
35.142857142935.1428571429
35.285714285735.2857142857
35.428571428635.4285714286
35.571428571435.5714285714
35.714285714335.7142857143
35.857142857135.8571428571
3636
36.142857142936.1428571429
36.285714285736.2857142857
36.428571428636.4285714286
36.571428571436.5714285714
36.714285714336.7142857143
36.857142857136.8571428571
3737
37.142857142937.1428571429
37.285714285737.2857142857
37.428571428637.4285714286
37.571428571437.5714285714
37.714285714337.7142857143
37.857142857137.8571428571
3838
38.142857142938.1428571429
38.285714285738.2857142857
38.428571428638.4285714286
38.571428571438.5714285714
38.714285714338.7142857143
38.857142857138.8571428571
3939
39.142857142939.1428571429
39.285714285739.2857142857
39.428571428639.4285714286
39.571428571439.5714285714
39.714285714339.7142857143
39.857142857139.8571428571
4040
40.142857142940.1428571429
40.285714285740.2857142857
40.428571428640.4285714286
40.571428571440.5714285714
40.714285714340.7142857143
40.857142857140.8571428571
4141
41.142857142941.1428571429
41.285714285741.2857142857
41.428571428641.4285714286
41.571428571441.5714285714
41.714285714341.7142857143
41.857142857141.8571428571
4242
42.142857142942.1428571429
42.285714285742.2857142857
42.428571428642.4285714286
42.571428571442.5714285714
42.714285714342.7142857143
42.857142857142.8571428571
4343
43.142857142943.1428571429
43.285714285743.2857142857
43.428571428643.4285714286
43.571428571443.5714285714
43.714285714343.7142857143
43.857142857143.8571428571
4444
44.142857142944.1428571429
44.285714285744.2857142857
44.428571428644.4285714286
44.571428571444.5714285714
44.714285714344.7142857143
44.857142857144.8571428571
4545
45.142857142945.1428571429
45.285714285745.2857142857
45.428571428645.4285714286
45.571428571445.5714285714
45.714285714345.7142857143
45.857142857145.8571428571
4646
46.142857142946.1428571429
46.285714285746.2857142857
46.428571428646.4285714286
46.571428571446.5714285714
46.714285714346.7142857143
46.857142857146.8571428571
4747
47.142857142947.1428571429
47.285714285747.2857142857
47.428571428647.4285714286
47.571428571447.5714285714
47.714285714347.7142857143
47.857142857147.8571428571
4848
48.142857142948.1428571429
48.285714285748.2857142857
48.428571428648.4285714286
48.571428571448.5714285714
48.714285714348.7142857143
48.857142857148.8571428571
4949
49.142857142949.1428571429
49.285714285749.2857142857
49.428571428649.4285714286
49.571428571449.5714285714
49.714285714349.7142857143
49.857142857149.8571428571
5050
50.142857142950.1428571429
50.285714285750.2857142857
50.428571428650.4285714286
50.571428571450.5714285714
50.714285714350.7142857143
50.857142857150.8571428571
5151
51.142857142951.1428571429
51.285714285751.2857142857
51.428571428651.4285714286
51.571428571451.5714285714
51.714285714351.7142857143
51.857142857151.8571428571
5252
IDeg OD (n=753)
IGlar OD (n=251)
0
0
0.0146082337
0.0199203187
0.0279061061
0.0398406375
0.0438848011
0.0478087649
0.0611950541
0.0677290837
0.0891577705
0.1035856574
0.1344307399
0.1235856574
0.1783721513
0.1435856574
0.2076664256
0.1757141714
0.2236451207
0.199810557
0.24634205
0.2239069425
0.2663687522
0.2480033281
0.2984114759
0.2720997136
0.3277839725
0.3283246132
0.3599124866
0.3684852558
0.382670184
0.4046298341
0.4041466941
0.4126943502
0.4202540767
0.4247911244
0.4430728686
0.4449524147
0.4873681706
0.4772104792
0.5437440095
0.5457588663
0.5827749651
0.5941459631
0.6110387605
0.6183395115
0.6299066851
0.650597576
0.6487746096
0.6828556405
0.6676425341
0.7070491889
0.720203181
0.7594685438
0.7646775746
0.7997911244
0.8146100982
0.8562427373
0.8417103692
0.8643072534
0.8688106402
0.8885008018
0.8837562924
0.9046951338
0.8960011903
0.9370837978
0.9408991495
0.9735210447
0.9844365645
1.0302012067
1.0388583332
1.0706870366
1.0742324828
1.0909299516
1.0932801019
1.1314157816
1.1123277209
1.1516586966
1.1382132795
1.1799987775
1.1804476119
1.2407275225
1.240393116
1.2933591014
1.2990561447
1.3581364293
1.3359413906
1.3824279273
1.3591654343
1.4067194253
1.3783172811
1.4270446286
1.4098241304
1.4595649538
1.4481802948
1.4880202383
1.5070844044
1.56119097
1.5481802948
1.6018413765
1.5687564265
1.6302966611
1.5838455897
1.6587519456
1.611280432
1.6953373115
1.63597179
1.7278576367
1.673008827
1.7888332464
1.7141610904
1.8904592627
1.7609286282
1.9433047912
1.7926527661
1.9718762197
1.821658291
1.9882027503
1.8437577385
2.0249374442
1.8741444789
2.0494272401
1.9224870203
2.0902435667
1.9722107772
2.1476206158
2.0206201825
2.204997665
2.0649415121
2.2459812716
2.0926423431
2.2828665175
2.130038465
2.3033583208
2.157739296
2.3279484847
2.2089858334
2.3812271732
2.2643874955
2.4429555683
2.3128639498
2.4717621526
2.3517528387
2.5046839633
2.3712514459
2.5378789841
2.4075136495
2.5669246272
2.4381970526
2.6084184032
2.4898009577
2.6540615567
2.5428735834
2.7038540878
2.6085160415
2.7536466189
2.6393283665
2.7785428845
2.6631712837
2.8202095512
2.6954746545
2.8452095512
2.7362622776
2.8868762178
2.7995534168
2.9452095512
2.8770182056
3.0452095512
2.927793946
3.1163392583
2.9561627404
3.1372597604
2.9703672858
3.1958371662
2.9902819373
3.23349407
3.0116190639
3.2962555763
3.0600521123
3.3757534842
3.1213930539
3.4678036934
3.1628216253
3.5224255422
3.1942951589
3.5476356262
3.2186504598
3.5602938541
3.2601977377
3.5940491283
3.2989351839
3.6320238119
3.3505851122
3.7290702254
3.4022350404
3.783922546
3.4482120519
3.8303360481
3.4856221239
3.872530141
3.5129996455
3.8851883688
3.5389362449
3.9147242338
3.5735183775
3.9569183266
3.6282734207
4.037087103
3.668619242
4.1045976515
3.7249776235
4.1552305629
3.7626042516
4.1847664279
3.7814448313
4.23117993
3.8003127558
4.2649352043
3.8380486049
4.3115453738
3.8801385904
4.3751046958
3.941185102
4.476799611
3.9993246369
4.5704166323
4.0414757997
4.6214804621
4.077813009
4.6810549302
4.1039757997
4.7150974834
4.128721069
4.761905994
4.1927676483
4.8087145047
4.262840641
4.8640336536
4.3226946556
4.9278634408
4.3577311519
4.9576506749
4.3796609765
4.9831825898
4.4176726724
5.0002038664
4.4425264736
5.0385017387
4.5024679941
5.1193528025
4.555099573
5.1834553666
4.6048071753
5.251831435
4.6457428479
5.2774724607
4.6735206256
5.3159339991
4.6925543006
5.3330280162
4.7218368775
5.3586690419
4.7790216282
5.4441391273
4.846668687
5.5125151957
4.8849602923
5.5811847236
4.9070516031
5.6242881719
4.9424498332
5.6589202065
4.9646064063
5.6935522411
5.0015340281
5.7368422844
5.050278489
5.7758033234
5.1168465363
5.849396397
5.1701009742
5.9186604662
5.2041750483
5.957790901
5.2382996774
5.9882256836
5.2665314753
6.005616988
5.2903056209
6.0360517706
5.351226869
6.0969213358
5.4032328126
6.1969213358
5.4478093356
6.2969213358
5.4760411335
6.3317039445
5.5102164678
6.3751822054
5.5354764976
6.4230082923
5.5696518319
6.4664865532
5.6097707026
6.5621387271
5.6796072554
6.6273561184
5.733099083
6.6882256836
5.7689199785
6.7012691619
5.7928005755
6.723103223
5.8166811726
6.7580377208
5.833099083
6.7973390309
5.8778752024
6.8410071532
5.9257077884
6.9196097732
5.9810142159
6.97201152
6.0199947256
6.9938455811
6.0470217526
7.0375137034
6.0755502812
7.0811818257
6.1085833142
7.1204831357
6.1567760853
7.1859853191
6.2185230732
7.2427538781
6.2757519889
7.3169896859
6.3225797835
7.3654478357
6.3391960977
7.3962848401
6.3664275651
7.4579588489
6.4012233291
7.4799852806
6.4556862641
7.5592804348
6.5056862641
7.62535973
6.549625658
7.7222760295
6.5890195974
7.7398971749
6.614816259
7.7707341793
6.643647822
7.7971658974
6.677031737
7.8412187608
6.7423812811
7.9249192013
6.8093523617
8.0350513599
6.8642304105
8.1231570868
6.8993449143
8.1672099502
6.9375128533
8.1849090653
6.969573922
8.1937586228
6.9863678151
8.2247320741
7.0092685785
8.2778294193
7.0321693418
8.3176524281
7.0504899525
8.357475437
7.073460856
8.3795993308
7.0903061853
8.4017232246
7.1071515145
8.4061480033
7.1285910245
8.4415462334
7.1484991409
8.4990683573
7.1867839801
8.5565904812
7.223593796
8.6052630476
7.255802385
8.6362364989
7.27880852
8.6583603927
7.2864772316
8.6760595078
7.2910784586
8.7026081803
7.3048821396
8.7291568529
7.3186858206
8.7557055255
7.3340232439
8.7778294193
7.3478269249
8.7999533131
7.3647240063
8.8220772069
7.3862293826
8.8487438735
7.4061986607
8.8842994291
7.45228161
8.9598549846
7.492220166
9.0442994291
7.5260663199
9.0800137148
7.5383740122
9.0889422862
7.5537586276
9.106879506
7.5629893968
9.1203324208
7.5706817045
9.1562068602
7.5937586276
9.1920812997
7.6076047814
9.2100185194
7.6399124737
9.236924349
7.6568355506
9.2683144835
7.6737586276
9.2952203131
7.6845278583
9.3266104477
7.6983740122
9.371453497
7.7352970891
9.4073279365
7.7815220506
9.4656239006
7.8231887173
9.5284041696
7.8463726431
9.568762914
7.8587374035
9.5911844387
7.8711213044
7.8896971558
9.6001530486
7.8958891063
9.6270588782
7.9036290444
9.6405723917
7.9144649577
9.6675994187
7.9299688336
9.6856174367
7.9470230972
9.7081399592
7.9640773608
9.7216534728
7.9702789112
9.7441759953
8.0105889887
9.7982300493
8.055550229
9.8477795989
8.0943099189
9.8973291484
8.1129434593
9.9243561755
8.1331297947
9.955887707
8.1517633351
9.973905725
8.1595273102
9.9964282475
8.1766080556
10.009941761
8.1936888009
10.0369687881
8.2138751363
10.0414732926
8.2402726518
10.0504823016
8.2511422171
10.0820138331
8.2713285525
10.1225543737
8.2899620928
10.1585904097
8.3210179935
10.2171489682
8.3614534522
10.2531850043
8.4003942622
10.3342660854
8.4144129538
10.3612931124
8.4331045426
10.3793111304
8.4518545426
10.4109853386
8.4643545426
10.4336097729
8.4784170426
10.4517093205
8.4971670426
10.4788586417
8.5096670426
10.5105328499
8.5268545426
10.5286323974
8.5362295426
10.5557817186
8.5612295426
10.5829310399
8.5940933923
10.5965057005
8.6364131416
10.6734287775
8.6677611039
10.7367771938
8.7007281369
10.7731408301
8.7195960614
10.7958681029
8.738463986
10.8185953756
8.7573616238
10.8322317392
8.7825584742
10.8595044665
8.8030309151
10.8776862847
8.8156293403
10.9095044665
8.8376765844
10.9185953756
8.8534246159
10.9322317392
8.8738970568
10.9504135574
8.8959443009
10.964049921
8.9195663482
10.9958681029
8.9542120175
11.0867771938
9.0077553246
11.1458681029
9.0502750096
11.1825653506
9.0771737438
11.255959846
9.100907921
11.3064185616
9.1151484273
11.3431158093
9.1325534906
11.3568772772
9.1499585539
11.3660515891
9.1673636172
11.379813057
9.1768572881
11.4027488368
9.1910977944
11.4165103047
9.2053383007
11.4348589285
9.222743364
11.4577947084
9.2369838703
11.4944919561
9.2828699463
11.5220148918
9.3319205792
11.5770607634
9.3604015919
11.6458681029
9.3857180476
11.6779781946
9.4062876678
11.6871947845
9.4268572881
11.7102362591
9.4379507904
11.719452849
9.453798651
11.7378860287
9.4680617255
11.7609275034
9.4775704418
11.7748163922
9.5092661629
11.7794460219
9.5314531676
11.7933349108
9.5488858142
11.8303719478
9.5679032469
11.8488904663
9.6091076843
11.8998163922
9.6518969077
11.9368534293
9.688346987
11.9694115688
9.7105692092
11.9973185456
9.7169184155
12.0112720339
9.7423152409
12.0205743595
9.7645374632
12.0484813363
9.7835850822
12.0577836618
9.7915215901
12.076388313
9.8058073044
12.0903418014
9.8248549235
12.0949929642
9.8407279393
12.1463948333
9.8470771457
12.1604793404
9.8725143476
12.1745638474
9.9091385514
12.2449863826
9.9441703986
12.3013244108
9.9728328189
12.3482727676
9.9887563858
12.357662439
10.0078646661
12.385831453
10.0142442514
12.3999159601
10.0301932147
12.4046107958
10.0541166597
12.4140004671
10.0732554157
12.4515591526
10.0860145863
12.4703384953
10.0971788606
12.4938126737
10.1147227203
12.5125920164
10.1290767873
12.5266765235
10.1450257506
12.5548455375
10.1625696102
12.5970990587
10.2008471222
12.6299629084
10.2375297378
12.6771327198
10.2599297378
12.7101515877
10.2807297378
12.7337364933
10.2887297378
12.7667553613
10.3095297378
12.7997742292
10.3191297378
12.8375100782
10.3447297378
12.8422270594
10.3527297378
12.8516610216
10.3655708293
12.8610949839
10.3784325657
12.8893968707
10.3977562372
12.9176987575
10.4219108265
12.9460006443
10.4525066397
12.9931704556
10.4831024529
13.0309063047
10.5249704079
13.0733591349
10.5507353032
13.0969440405
10.5717030451
13.1063780028
10.5942836903
13.1252459273
10.6200901419
13.1393968707
10.6378320774
13.1582647952
10.6523482064
13.1771327198
10.6700901419
13.2055687387
10.6879763208
13.2340047577
10.6994329492
13.2582766023
10.7208850945
13.282548447
10.7459268307
13.3168621725
10.8020492797
13.3618621725
10.8556207082
13.4194537955
10.9129977574
13.4697682609
Conf. hypo
weekIDeg_ODIGlar_ODIDeg OD (n=753)IGlar OD (n=251)
00000
0.14285714290.01460823370.01992031871.46082337321.9920318725
0.28571428570.02790610610.03984063752.79061060723.984063745
0.42857142860.04388480110.04780876494.38848011454.780876494
0.57142857140.06119505410.06772908376.11950541416.7729083665
0.71428571430.08915777050.10358565748.91577705210.3585657371
0.85714285710.13443073990.123585657413.443073989412.3585657371
10.17837215130.143585657417.837215134514.3585657371
1.14285714290.20766642560.175714171420.766642564617.5714171427
1.28571428570.22364512070.19981055722.364512071919.9810556969
1.42857142860.246342050.223906942524.634204995822.3906942511
1.57142857140.26636875220.248003328126.636875222824.8003328053
1.71428571430.29841147590.272099713629.841147585927.2099713595
1.85714285710.32778397250.328324613232.778397252232.8324613194
20.35991248660.368485255835.991248657836.8485255764
2.14285714290.3826701840.404629834138.267018403440.4629834077
2.28571428570.40414669410.412694350240.414669410241.2694350206
2.42857142860.42025407670.424791124442.025407665242.47911244
2.57142857140.44307286860.444952414744.307286859844.4952414723
2.71428571430.48736817060.477210479248.736817061247.7210479239
2.85714285710.54374400950.545758866354.374400953854.5758866335
30.58277496510.594145963158.277496512359.414596311
3.14285714290.61103876050.618339511561.103876054761.8339511497
3.28571428570.62990668510.65059757662.990668507665.0597576013
3.42857142860.64877460960.682855640564.877460960468.2855640529
3.57142857140.66764253410.707049188966.764253413270.7049188916
3.71428571430.7202031810.759468543872.020318103275.9468543755
3.85714285710.76467757460.799791124476.467757456379.97911244
40.81461009820.856242737381.46100981885.6242737303
4.14285714290.84171036920.864307253484.171036918386.4307253432
4.28571428570.86881064020.888500801886.881064018688.8500801819
4.42857142860.88375629240.904695133888.375629235990.4695133803
4.57142857140.89600119030.937083797889.600119031993.7083797771
4.71428571430.94089914950.973521044794.089914950297.3521044734
4.85714285710.98443656451.030201206798.4436564468103.0201206678
51.03885833321.0706870366103.8858333176107.0687036637
5.14285714291.07423248281.0909299516107.4232482836109.0929951617
5.28571428571.09328010191.1314157816109.3280101883113.1415781576
5.42857142861.11232772091.1516586966111.2327720931115.1658696556
5.57142857141.13821327951.1799987775113.8213279514117.9998777528
5.71428571431.18044761191.2407275225118.0447611939124.0727522467
5.85714285711.2403931161.2933591014124.0393116026129.3359101414
61.29905614471.3581364293129.9056144676135.813642935
6.14285714291.33594139061.3824279273133.5941390577138.2427927325
6.28571428571.35916543431.4067194253135.9165434293140.6719425301
6.42857142861.37831728111.4270446286137.8317281078142.7044628553
6.57142857141.40982413041.4595649538140.9824130393145.9564953756
6.71428571431.44818029481.4880202383144.8180294777148.8020238309
6.85714285711.50708440441.56119097150.7084404366156.1190970017
71.54818029481.6018413765154.8180294777160.1841376521
7.14285714291.56875642651.6302966611156.8756426464163.0296661073
7.28571428571.58384558971.6587519456158.3845589702165.8751945626
7.42857142861.6112804321.6953373115161.1280431951169.533731148
7.57142857141.635971791.7278576367163.5971789976172.7857636683
7.71428571431.6730088271.7888332464167.3008827013178.8833246439
7.85714285711.71416109041.8904592627171.4161090387189.0459262699
81.76092862821.9433047912176.0928628214194.3304791155
8.14285714291.79265276611.9718762197179.2652766145197.1876219726
8.28571428571.8216582911.9882027503182.1658291007198.8202750338
8.42857142861.84375773852.0249374442184.3757738521202.4937444216
8.57142857141.87414447892.0494272401187.4144478852204.9427240134
8.71428571431.92248702032.0902435667192.2487020289209.0243566665
8.85714285711.97221077722.1476206158197.2210777195214.7620615845
92.02062018252.204997665202.0620182451220.4997665026
9.14285714292.06494151212.2459812716206.4941512091224.5981271583
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45.28571428579.840727939312.1463948333984.07279393431214.6394833319
45.42857142869.847077145712.1604793404984.70771456921216.0479340361
45.57142857149.872514347612.1745638474987.251434761217.4563847403
45.71428571439.909138551412.2449863826990.91385514211224.4986382614
45.85714285719.944170398612.3013244108994.41703985551230.1324410783
469.972832818912.3482727676997.28328189371234.8272767591
46.14285714299.988756385812.357662439998.87563858161235.7662438952
46.285714285710.007864666112.3858314531000.78646660711238.5831453037
46.428571428610.014244251412.39991596011001.42442513981239.9915960079
46.571428571410.030193214712.40461079581003.01932147151240.461079576
46.714285714310.054116659712.41400046711005.41166596911241.4000467122
46.857142857110.073255415712.45155915261007.32554156721245.1559152567
4710.086014586312.47033849531008.60145863261247.0338495291
47.142857142910.097178860612.49381267371009.71788606481249.3812673694
47.285714285710.114722720312.51259201641011.47227202971251.2592016417
47.428571428610.129076787312.52667652351012.90767872831252.667652346
47.571428571410.145025750612.55484553751014.502575061255.4845537544
47.714285714310.162569610212.59709905871016.2569610251259.7099058671
47.857142857110.200847122212.62996290841020.08471222111262.9962908436
4810.237529737812.67713271981023.75297378411267.7132719757
48.142857142910.259929737812.71015158771025.99297378411271.0151587681
48.285714285710.280729737812.73373649331028.07297378411273.3736493342
48.428571428610.288729737812.76675536131028.87297378411276.6755361266
48.571428571410.309529737812.79977422921030.95297378411279.9774229191
48.714285714310.319129737812.83751007821031.91297378411283.7510078247
48.857142857110.344729737812.84222705941034.47297378411284.2227059379
4910.352729737812.85166102161035.27297378411285.1661021644
49.142857142910.365570829312.86109498391036.55708293341286.1094983908
49.285714285710.378432565712.88939687071037.84325656681288.93968707
49.428571428610.397756237212.91769875751039.77562371661291.7698757493
49.571428571410.421910826512.94600064431042.19108265381294.6000644285
49.714285714310.452506639712.99317045561045.25066397431299.3170455606
49.857142857110.483102452913.03090630471048.31024529471303.0906304663
5010.524970407913.07335913491052.49704078591307.3359134851
50.142857142910.550735303213.09694404051055.07353031891309.6944040512
50.285714285710.571703045113.10637800281057.17030451241310.6378002776
50.428571428610.594283690313.12524592731059.42836902851312.5245927304
50.571428571410.620090141913.13939687071062.00901418981313.93968707
50.714285714310.637832077413.15826479521063.78320773821315.8264795228
50.857142857110.652348206413.17713271981065.23482064141317.7132719757
5110.670090141913.20556873871067.00901418981320.5568738714
51.142857142910.687976320813.23400475771068.7976320761323.4004757672
51.285714285710.699432949213.25827660231069.94329492381325.8276602332
51.428571428610.720885094513.2825484471072.08850944531328.2548446992
51.571428571410.745926830713.31686217251074.5926830681331.6862172482
51.714285714310.802049279713.36186217251080.20492796591336.1862172482
51.857142857110.855620708213.41945379551085.5620708231341.9453795519
5210.912997757413.46976826091091.29977574111346.9768260928
Conf. hypo
IDeg OD (n=753)
IGlar OD (n=251)
Time (weeks)
Confirmed hypoglycaemia (cumulative events per 100 PYE)
-
Nocturnal confirmed hypoglycaemia
SASComparisons: Estimates adjusted for multiple covariates
25% risk reduction, p=0.04
Noc
turn
al c
onfir
med
hyp
ogly
caem
ia
(cum
ulat
ive
even
ts p
er 1
00 p
atie
nts)
Time (weeks)
IDeg OD (n=753)IGlar OD (n=251)
Garber A et al. Lancet 2012;379:1498-507
Chart1
00
0.14285714290.1428571429
0.28571428570.2857142857
0.57142857140.5714285714
0.71428571430.7142857143
0.85714285710.8571428571
11
1.14285714291.1428571429
1.28571428571.2857142857
1.42857142861.4285714286
1.57142857141.5714285714
1.71428571431.7142857143
1.85714285711.8571428571
22
2.14285714292.1428571429
2.28571428572.2857142857
2.42857142862.4285714286
2.57142857142.5714285714
2.71428571432.7142857143
2.85714285712.8571428571
33
3.14285714293.1428571429
3.28571428573.2857142857
3.42857142863.4285714286
3.57142857143.5714285714
3.71428571433.7142857143
3.85714285713.8571428571
44
4.14285714294.1428571429
4.28571428574.2857142857
4.42857142864.4285714286
4.57142857144.5714285714
4.71428571434.7142857143
4.85714285714.8571428571
55
5.14285714295.1428571429
5.28571428575.2857142857
5.42857142865.4285714286
5.57142857145.5714285714
5.71428571435.7142857143
5.85714285715.8571428571
66
6.14285714296.1428571429
6.28571428576.2857142857
6.42857142866.4285714286
6.57142857146.5714285714
6.71428571436.7142857143
6.85714285716.8571428571
77
7.14285714297.1428571429
7.28571428577.2857142857
7.42857142867.4285714286
7.57142857147.5714285714
7.71428571437.7142857143
7.85714285717.8571428571
88
8.14285714298.1428571429
8.28571428578.2857142857
8.42857142868.4285714286
8.57142857148.5714285714
8.71428571438.7142857143
8.85714285718.8571428571
99
9.14285714299.1428571429
9.28571428579.2857142857
9.42857142869.4285714286
9.57142857149.5714285714
9.71428571439.7142857143
9.85714285719.8571428571
1010
10.142857142910.1428571429
10.285714285710.2857142857
10.428571428610.4285714286
10.571428571410.5714285714
10.714285714310.7142857143
10.857142857110.8571428571
1111
11.142857142911.1428571429
11.285714285711.2857142857
11.428571428611.4285714286
11.571428571411.5714285714
11.714285714311.7142857143
11.857142857111.8571428571
1212
12.142857142912.1428571429
12.285714285712.2857142857
12.428571428612.4285714286
12.571428571412.5714285714
12.714285714312.7142857143
12.857142857112.8571428571
1313
13.142857142913.1428571429
13.285714285713.2857142857
13.428571428613.4285714286
13.571428571413.5714285714
13.714285714313.7142857143
13.857142857113.8571428571
1414
14.142857142914.1428571429
14.285714285714.2857142857
14.428571428614.4285714286
14.571428571414.5714285714
14.714285714314.7142857143
14.857142857114.8571428571
1515
15.142857142915.1428571429
15.285714285715.2857142857
15.428571428615.4285714286
15.571428571415.5714285714
15.714285714315.7142857143
15.857142857115.8571428571
1616
16.142857142916.1428571429
16.285714285716.2857142857
16.428571428616.4285714286
16.571428571416.5714285714
16.714285714316.7142857143
16.857142857116.8571428571
1717
17.142857142917.1428571429
17.428571428617.4285714286
17.571428571417.5714285714
17.714285714317.7142857143
17.857142857117.8571428571
1818
18.142857142918.1428571429
18.285714285718.2857142857
18.428571428618.4285714286
18.571428571418.5714285714
18.714285714318.7142857143
18.857142857118.8571428571
1919
19.142857142919.1428571429
19.285714285719.2857142857
19.428571428619.4285714286
19.571428571419.5714285714
19.714285714319.7142857143
19.857142857119.8571428571
2020
20.142857142920.1428571429
20.285714285720.2857142857
20.428571428620.4285714286
20.571428571420.5714285714
20.714285714320.7142857143
20.857142857120.8571428571
2121
21.142857142921.1428571429
21.285714285721.2857142857
21.428571428621.4285714286
21.571428571421.5714285714
21.714285714321.7142857143
21.857142857121.8571428571
2222
22.142857142922.1428571429
22.285714285722.2857142857
22.428571428622.4285714286
22.571428571422.5714285714
22.714285714322.7142857143
22.857142857122.8571428571
2323
23.142857142923.1428571429
23.285714285723.2857142857
23.428571428623.4285714286
23.571428571423.5714285714
23.714285714323.7142857143
23.857142857123.8571428571
2424
24.142857142924.1428571429
24.285714285724.2857142857
24.428571428624.4285714286
24.571428571424.5714285714
24.714285714324.7142857143
24.857142857124.8571428571
2525
25.142857142925.1428571429
25.285714285725.2857142857
25.428571428625.4285714286
25.571428571425.5714285714
25.714285714325.7142857143
25.857142857125.8571428571
2626
26.142857142926.1428571429
26.285714285726.2857142857
26.428571428626.4285714286
26.571428571426.5714285714
26.714285714326.7142857143
2727
27.142857142927.1428571429
27.285714285727.2857142857
27.428571428627.4285714286
27.571428571427.5714285714
27.714285714327.7142857143
27.857142857127.8571428571
2828
28.142857142928.1428571429
28.285714285728.2857142857
28.428571428628.4285714286
28.714285714328.7142857143
28.857142857128.8571428571
2929
29.142857142929.1428571429
29.285714285729.2857142857
29.428571428629.4285714286
29.571428571429.5714285714
29.714285714329.7142857143
29.857142857129.8571428571
3030
30.285714285730.2857142857
30.428571428630.4285714286
30.571428571430.5714285714
30.714285714330.7142857143
30.857142857130.8571428571
3131
31.142857142931.1428571429
31.285714285731.2857142857
31.428571428631.4285714286
31.571428571431.5714285714
31.714285714331.7142857143
31.857142857131.8571428571
3232
32.142857142932.1428571429
32.285714285732.2857142857
32.571428571432.5714285714
32.714285714332.7142857143
32.857142857132.8571428571
3333
33.142857142933.1428571429
33.285714285733.2857142857
33.428571428633.4285714286
33.571428571433.5714285714
33.714285714333.7142857143
33.857142857133.8571428571
3434
34.142857142934.1428571429
34.285714285734.2857142857
34.428571428634.4285714286
34.571428571434.5714285714
34.714285714334.7142857143
3535
35.142857142935.1428571429
35.285714285735.2857142857
35.428571428635.4285714286
35.571428571435.5714285714
35.714285714335.7142857143
35.857142857135.8571428571
3636
36.142857142936.1428571429
36.285714285736.2857142857
36.428571428636.4285714286
36.571428571436.5714285714
36.714285714336.7142857143
36.857142857136.8571428571
3737
37.142857142937.1428571429
37.285714285737.2857142857
37.428571428637.4285714286
37.571428571437.5714285714
37.714285714337.7142857143
37.857142857137.8571428571
3838
38.142857142938.1428571429
38.285714285738.2857142857
38.428571428638.4285714286
38.571428571438.5714285714
38.714285714338.7142857143
38.857142857138.8571428571
3939
39.142857142939.1428571429
39.285714285739.2857142857
39.428571428639.4285714286
39.571428571439.5714285714
39.714285714339.7142857143
39.857142857139.8571428571
4040
40.142857142940.1428571429
40.285714285740.2857142857
40.428571428640.4285714286
40.571428571440.5714285714
40.857142857140.8571428571
4141
41.142857142941.1428571429
41.285714285741.2857142857
41.428571428641.4285714286
41.571428571441.5714285714
41.714285714341.7142857143
41.857142857141.8571428571
4242
42.142857142942.1428571429
42.285714285742.2857142857
42.428571428642.4285714286
42.714285714342.7142857143
42.857142857142.8571428571
4343
43.142857142943.1428571429
43.285714285743.2857142857
43.428571428643.4285714286
43.571428571443.5714285714
43.714285714343.7142857143
43.857142857143.8571428571
4444
44.142857142944.1428571429
44.428571428644.4285714286
44.571428571444.5714285714
44.714285714344.7142857143
44.857142857144.8571428571
4545
45.142857142945.1428571429
45.285714285745.2857142857
45.428571428645.4285714286
45.571428571445.5714285714
45.714285714345.7142857143
45.857142857145.8571428571
4646
46.142857142946.1428571429
46.285714285746.2857142857
46.428571428646.4285714286
46.571428571446.5714285714
46.714285714346.7142857143
46.857142857146.8571428571
4747
47.142857142947.1428571429
47.285714285747.2857142857
47.428571428647.4285714286
47.571428571447.5714285714
47.714285714347.7142857143
47.857142857147.8571428571
4848
48.142857142948.1428571429
48.285714285748.2857142857
48.571428571448.5714285714
48.714285714348.7142857143
48.857142857148.8571428571
4949
49.142857142949.1428571429
49.285714285749.2857142857
49.428571428649.4285714286
49.571428571449.5714285714
49.714285714349.7142857143
49.857142857149.8571428571
5050
50.142857142950.1428571429
50.285714285750.2857142857
50.428571428650.4285714286
50.571428571450.5714285714
50.714285714350.7142857143
50.857142857150.8571428571
5151
51.142857142951.1428571429
51.285714285751.2857142857
51.571428571451.5714285714
51.714285714351.7142857143
51.857142857151.8571428571
5252
IDeg OD (n=753)
IGlar OD (n=251)
0
0
0.0013280212
0.0079681275
0.0039875957
0.0119521912
0.0066507116
0.0106453853
0.015936255
0.015971617
0.023936255
0.0226294066
0.0279556383
0.0319683835
0.0292871962
0.0359844478
0.0319574232
0.040000512
0.0346276502
0.0372978772
0.0413032176
0.0520487048
0.04665797
0.0600808333
0.0533514104
0.0640968976
0.057378256
0.0600628198
0.0721614137
0.0614051017
0.0761936717
0.0654319473
0.0842581879
0.0721433567
0.092322704
0.0761810418
0.1003872201
0.0815646218
0.1044194782
0.0842600396
0.1124839943
0.0869554574
0.1165162524
0.0909985841
0.1286130266
0.0950417108
0.1366775427
0.1058233819
0.1085224373
0.1447420588
0.1139424915
0.1180075321
0.1487743169
0.1568714829
0.1193680763
0.1609200659
0.1207286206
0.1248102532
0.1649686489
0.1302524301
0.1730658149
0.1397762396
0.1811629809
0.1852115639
0.1438578723
0.1892601469
0.1493074635
0.1933087299
0.1547570548
0.2014058959
0.1588442483
0.2054544788
0.1670297872
0.2135516448
0.1711281478
0.2176002278
0.1738603883
0.2216488108
0.2257138515
0.1779699773
0.1793398403
0.2297788921
0.1807097033
0.2460390547
0.1861891554
0.1889326396
0.2501040954
0.1916761238
0.1944196081
0.1971630923
0.254169136
0.1999065765
0.2622992173
0.2012783186
0.2785593799
0.2067803819
0.2826244206
0.2122976233
0.2907876859
0.2178224851
0.2948693185
0.2192037006
0.2989509512
0.223347347
0.2302534244
0.2343970708
0.3071476725
0.2413127001
0.3194427545
0.2482379079
0.2551631156
0.3235411151
0.2593182403
0.2620883234
0.266243448
0.3317378364
0.2745536973
0.2814789051
0.3399682891
0.2856455718
0.3481987418
0.2898238447
0.356497497
0.292613245
0.3606468746
0.2954026453
0.3037708461
0.3647962522
0.3135473824
0.3730950074
0.3191339746
0.3772443849
0.3247440728
0.3814110516
0.3317665447
0.3373924238
0.3430183028
0.3980777183
0.3486521056
0.3542938546
0.41481412
0.3628044929
0.4189982204
0.3642249474
0.4231823208
0.3670698976
0.3684923727
0.435734622
0.3741985068
0.4482869233
0.381341364
0.4566902846
0.3884944398
0.4608919653
0.392792434
0.4693307839
0.3942250988
0.4028334202
0.4071375809
0.4186153427
0.4243624691
0.4819890117
0.4258013181
0.4904278303
0.4301240846
0.4315650068
0.4358877734
0.4459742287
0.4488560731
0.4988666489
0.4546364199
0.4575307759
0.461878602
0.5115248767
0.4662327385
0.5199636953
0.4734896325
0.4763923901
0.5369128478
0.4851133204
0.5538620004
0.495287739
0.570883277
0.5054621576
0.5751385961
0.5083691343
0.5793939153
0.5127295994
0.5836492344
0.5141852035
0.5185520157
0.5243914318
0.5316907019
0.5921598727
0.5375301179
0.5433780711
0.547764036
0.5964151919
0.5536119893
0.5565359659
0.6220562175
0.5623839191
0.630603226
0.5638459074
0.566769884
0.6348767303
0.5711622705
0.5740905282
0.6391502346
0.5799556309
0.6562442517
0.5887791603
0.660517756
0.5917246684
0.6691014469
0.5990884386
0.6820324814
0.6035132174
0.607944532
0.6863614858
0.6108987417
0.6950194944
0.6168071612
0.7036775031
0.6271621908
0.7080065074
0.6345586405
0.7123355117
0.6434475294
0.7166833378
0.6464148885
0.7210311639
0.6523584249
0.6568160772
0.6612737295
0.7384224683
0.6657313818
0.7558137726
0.6716749182
0.7688572509
0.6761325705
0.777552903
0.6805902228
0.7819007291
0.683561991
0.7905963813
0.6909914115
0.7992920335
0.6954490638
0.7028784843
0.8036398596
0.7117937889
0.7192564755
0.7222415501
0.7237340874
0.8080066718
0.7267191621
0.731196774
0.812373484
0.7356810789
0.8254739207
0.7446496888
0.7506466903
0.7566526963
0.8342075451
0.7611572008
0.8429411696
0.8516747941
0.7656752731
0.8604084185
0.7747114177
0.8735088552
0.7777234659
0.8953429163
0.7822551879
0.9129640617
0.7837657619
0.9261799207
0.7883043398
0.9305852071
0.7913300585
0.9438010661
0.9482063524
0.795875513
0.9526116388
0.798905816
0.8019361191
0.9570169251
0.8049710204
0.9614222115
0.8095233725
0.9658274978
0.8125582738
0.9746380705
0.8171175444
0.9834486432
0.8232058244
0.9878539295
0.8308277756
1.0010697886
0.8354079283
1.0098803613
0.839988081
0.8460949512
0.8476216688
1.01430514
0.8491483863
1.0275794763
0.853728539
0.8583227197
1.0320042551
0.8598541133
0.8629169004
0.8659796875
0.8690424747
0.875168049
0.8828367606
1.0408538126
0.8889717299
1.0452785913
0.8905054723
0.8920392146
0.8935729569
1.0497033701
0.8966404416
1.0541281489
0.8997079263
0.9012416686
0.9043138652
0.9058499635
1.0630170378
0.9073860618
0.9150665534
0.9196748483
1.0763503711
0.9227517714
1.0808146568
0.9242902329
0.9258286945
0.9289056175
1.0852989617
0.9350594637
0.9381363868
0.9396748483
0.9412133098
1.0987518765
1.1032361815
1.1077204864
0.9442902329
1.1166890963
0.947367156
1.1211734012
0.9489079881
1.1256577061
0.9519944078
1.1301420111
0.956631193
1.1391106209
0.9628135732
1.1480792308
0.9705535113
1.1525635357
1.1615321456
0.9721014989
0.9736494865
0.9767502617
1.1660366501
0.9783006493
1.1705411546
0.9798510369
1.1795501636
1.1930636771
1.1975681816
0.9814014245
1.2020726861
0.9829542195
0.9845070145
1.2110816951
0.9891653996
1.2200907042
0.9907181947
1.2290997132
0.9922709897
0.9938237847
0.9984821698
1.2381087222
1.0015877599
1.2426132267
1.0046933499
1.2471177312
1.00779894
1.2606312447
1.0155749898
1.2921627762
1.0186902546
1.020247887
1.2966672807
1.023372887
1.026497887
1.3011921676
1.029622887
1.031185387
1.3057170545
1.034310387
1.035872887
1.323816602
1.040560387
1.3328663758
1.0515150036
1.3419161495
1.0546497998
1.3509659233
1.0562171979
1.360015697
1.0624966328
1.3691066061
1.0640689598
1.3736520607
1.0672136139
1.0719380233
1.3781975152
1.0735128265
1.3918338788
1.0766624328
1.0782372359
1.4009247879
1.0813868422
1.410015697
1.0845364485
1.4145611516
1.0924104643
1.0939852674
1.4191066061
1.0955600706
1.10028448
1.4372884243
1.1034340863
1.4509247879
1.1144577084
1.4555119439
1.1255336578
1.4876220356
1.1286982147
1.5013835035
1.1302804932
1.5105578155
1.1334450502
1.5151449714
1.1350273286
1.1381918856
1.5197321274
1.1413564426
1.5243192833
1.142938721
1.5334935953
1.1445209995
1.5380807512
1.5426679072
1.1476855565
1.1524323919
1.5518422191
1.561016531
1.1571792274
1.565603687
1.1603437843
1.1635083413
1.1650931274
1.1714322716
1.5702119819
1.5794712412
1.1761866297
1.1793562018
1.5933601301
1.1825257739
1.1856953461
1.5979897597
1.1888649182
1.1952040624
1.6026409225
1.1983786656
1.6072920853
1.2015532687
1.2063151735
1.6165944109
1.2126643798
1.2142516814
1.6212455737
1.6258967365
1.2190135862
1.6305478993
1.2237754909
1.6445665908
1.2253627925
1.2269526177
1.6492614265
1.2333220444
1.2365067578
1.6586510979
1.2428761845
1.2444685412
1.6633459336
1.2476532546
1.6680407692
1.6727356049
1.2508430473
1.6774304406
1.2588175289
1.2636022179
1.6821252763
1.2651971142
1.686820112
1.2683869069
1.2699818032
1.6915149476
1.2715766996
1.2763613886
1.6962097833
1.2827409739
1.2843358702
1.7009267645
1.2875358702
1.7056437456
1.2907358702
1.2939358702
1.7103607267
1.2955358702
1.719794689
1.2971358702
1.7245116701
1.2987358702
1.7292286513
1.3003410067
1.7339456324
1.7386626135
1.3083925365
1.7433795947
1.3100028424
1.3132234543
1.7480965758
1.3148337603
1.7528135569
1.3196646782
1.757530538
1.324495596
1.3309472089
1.3357859186
1.3406246283
1.3422375315
1.7669645003
1.7717038368
1.345489564
1.7906611828
1.8003699206
1.8052718814
1.3522922851
1.8102718814
1.357649428
1.8259786877
1.363796969
1.8322679959
Noct. conf. hypo
trl_idweekIDeg_ODIGlar_ODIDeg OD (n=753)IGlar OD (n=251)
NN1250-358200000
NN1250-35820.14285714290.00132802120.00796812750.13280212480.796812749
NN1250-35820.28571428570.00398759570.01195219120.39875957161.1952191235
NN1250-35820.57142857140.00665071160.6650711562
NN1250-35820.71428571430.01064538530.0159362551.0645385331.593625498
NN1250-35820.85714285710.0159716170.0239362551.59716170212.393625498
NN1250-358210.02262940662.2629406635
NN1250-35821.14285714290.02795563830.03196838352.79556383263.1968383494
NN1250-35821.28571428570.02928719620.03598444782.92871962493.5984447751
NN1250-35821.42857142860.03195742320.0400005123.19574232184.0000512008
NN1250-35821.57142857140.03462765023.4627650188
NN1250-35821.71428571430.03729787723.7297877157
NN1250-35821.85714285710.04130321760.05204870484.13032176115.2048704779
NN1250-358220.046657970.06008083334.66579699546.0080833293
NN1250-35822.14285714290.05335141040.06409689765.33514103826.409689755
NN1250-35822.28571428570.0573782565.737825602
NN1250-35822.42857142860.06006281980.07216141376.00628197787.2161413679
NN1250-35822.57142857140.06140510170.07619367176.14051016577.6193671744
NN1250-35822.71428571430.06543194730.08425818796.54319472958.4258187873
NN1250-35822.85714285710.07214335670.0923227047.21433566919.2322704002
NN1250-358230.07618104180.10038722017.618104175110.0387220131
NN1250-35823.14285714290.08156462180.10441947828.156462183210.4419478196
NN1250-35823.28571428570.08426003960.11248399438.426003962211.2483994325
NN1250-35823.42857142860.08695545740.11651625248.695545741211.6516252389
NN1250-35823.57142857140.09099858410.12861302669.099858409612.8613026583
NN1250-35823.71428571430.09504171080.13667754279.504171078113.6677542712
NN1250-35823.85714285710.105823381910.582338194
NN1250-358240.10852243730.144742058810.85224372714.4742058841
NN1250-35824.14285714290.113942491511.3942491471
NN1250-35824.28571428570.11800753210.148774316911.800753212114.8774316905
NN1250-35824.42857142860.156871482915.6871482897
NN1250-35824.57142857140.11936807630.160920065911.936807633916.0920065893
NN1250-35824.71428571430.120728620612.0728620557
NN1250-35824.85714285710.12481025320.164968648912.48102532116.4968648889
NN1250-358250.13025243010.173065814913.025243008117.3065814881
NN1250-35825.14285714290.13977623960.181162980913.977623960418.1162980873
NN1250-35825.28571428570.185211563918.5211563869
NN1250-35825.42857142860.14385787230.189260146914.385787225718.9260146865
NN1250-35825.57142857140.14930746350.193308729914.930746353819.3308729861
NN1250-35825.71428571430.15475705480.201405895915.475705481920.1405895853
NN1250-35825.85714285710.15884424830.205454478815.884424827920.5454478849
NN1250-358260.16702978720.213551644816.702978716121.355164484
NN1250-35826.14285714290.17112814780.217600227817.112814781621.7600227836
NN1250-35826.28571428570.17386038830.221648810817.386038825322.1648810832
NN1250-35826.42857142860.225713851522.5713851483
NN1250-35826.57142857140.177969977317.7969977295
NN1250-35826.71428571430.17933984030.229778892117.933984030822.9778892133
NN1250-35826.85714285710.18070970330.246039054718.070970332224.6039054735
NN1250-358270.186189155418.6189155377
NN1250-35827.14285714290.18893263960.250104095418.893263960225.0104095385
NN1250-35827.28571428570.191676123819.1676123827
NN1250-35827.42857142860.194419608119.4419608052
NN1250-35827.57142857140.19716309230.25416913619.716309227725.4169136036
NN1250-35827.71428571430.19990657650.262299217319.990657650226.2299217336
NN1250-35827.85714285710.20127831860.278559379920.127831861427.8559379938
NN1250-358280.20678038190.282624420620.678038188828.2624420588
NN1250-35828.14285714290.21229762330.290787685921.229762326729.0787685895
NN1250-35828.28571428570.21782248510.294869318521.782248514629.4869318548
NN1250-35828.42857142860.21920370060.298950951221.920370061529.8950951201
NN1250-35828.57142857140.22334734722.3347347024
NN1250-35828.71428571430.230253424423.0253424372
NN1250-35828.85714285710.23439707080.307147672523.439707078130.7147672512
NN1250-358290.24131270010.319442754524.131270010331.9442754479
NN1250-35829.14285714290.248237907924.8237907859
NN1250-35829.28571428570.25516311560.323541115125.516311561632.3541115135
NN1250-35829.42857142860.259318240325.9318240269
NN1250-35829.57142857140.262088323426.2088323372
NN1250-35829.71428571430.2662434480.331737836426.624344802633.1737836447
NN1250-35829.85714285710.274553697327.4553697333
NN1250-3582100.28147890510.339968289128.147890508933.9968289121
NN1250-358210.14285714290.28564557180.348198741828.564557175634.8198741796
NN1250-358210.28571428570.28982384470.35649749728.982384473635.6497496983
NN1250-358210.42857142860.2926132450.360646874629.261324501536.0646874576
NN1250-358210.57142857140.295402645329.5402645294
NN1250-358210.71428571430.30377084610.364796252230.377084613136.479625217
NN1250-358210.85714285710.31354738240.373095007431.354738244437.3095007357
NN1250-3582110.319133974631.9133974623
NN1250-358211.14285714290.377244384937.724438495
NN1250-358211.28571428570.32474407280.381411051632.4744072838.1411051617
NN1250-358211.42857142860.331766544733.176654471
NN1250-358211.57142857140.337392423833.7392423753
NN1250-358211.71428571430.34301830280.398077718334.301830279739.8077718283
NN1250-358211.85714285710.348652105634.8652105614
NN1250-3582120.35429385460.4148141235.429385455641.4814119957
NN1250-358212.14285714290.36280449290.418998220436.280449285441.8998220375
NN1250-358212.28571428570.36422494740.423182320836.422494739942.3182320794
NN1250-358212.42857142860.367069897636.7069897613
NN1250-358212.57142857140.368492372736.8492372719
NN1250-358212.71428571430.43573462243.5734622049
NN1250-358212.85714285710.37419850680.448286923337.419850681344.8286923304
NN1250-3582130.3813413640.456690284638.134136395645.6690284649
NN1250-358213.14285714290.38849443980.460891965338.849443977946.0891965321
NN1250-358213.28571428570.3927924340.469330783939.279243404846.9330783886
NN1250-358213.42857142860.394225098839.4225098805
NN1250-358213.57142857140.402833420240.2833420182
NN1250-358213.71428571430.407137580940.7137580871
NN1250-358213.85714285710.418615342741.8615342707
NN1250-3582140.42436246910.481989011742.436246914448.1989011734
NN1250-358214.14285714290.42580131810.490427830342.580131806549.04278303
NN1250-358214.28571428570.430124084643.0124084635
NN1250-35