Download PowerPoint colour guidelines - E-Med

‫‪Slide No 1‬‬
‫אתגר הטיפול בסוכרת מסוג ‪2‬‬
‫מעל ‪ 50%‬מהחולים אינם מגיעים ליעדי האיזון‬
‫‪HbA1c>7%‬‬
‫‪Ford et al (NHANES). Diabetes Care. 2008; 31: 102–4‬‬
Slide No 2
‫רוב הטיפולים הקיימים גורמים לעלייה במשקל לאורך זמן‬
UKPDS: up to 8 kg in 12 years
ADOPT: up to 4.8 kg in 5 years
100
8
Insulin
(n=409)
7
6
96
5
Glibenclamide (n=277)
4
3
2
Weight (kg)
Change in weight (kg)
Treatment difference (95% CI)
Rosiglitazone vs. metformin
6.9 (6.3 tp 7.4); p<0.001
Rosiglitazone vs. glibenclamide,
2.5 (2.0 to 3.1); p<0.001
92
88
1
Metformin (n=342)
0
0
3
6
9
Years from randomisation
Conventional treatment (n=411);
diet initially then sulphonylureas, insulin
and/or metformin if FPG >15 mmol/L
12
0
0
1
2
3
Annualised slope (95% CI)
Rosiglitazone, 0.7 (0.6 to 0.8)
Metformin, -0.3 (-0.4 to -0.2)**
Glibenclamide, -0.2 (-0.3 to 0.0)**
UKPDS 34. Lancet 1998:352:854–65. n=at baseline; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43
4
Years
5
20
Patients with hypoglycaemia** (%)
Hypoglycaemia, events/patient/year*
Current treatments increase risk of
hypoglycaemia
15
10
5
0
Glargine
*All symptomatic hypoglycaemic events
NPH
45
39
40
35
30
p<0.05 glibenclamide
vs. rosiglitazone
25
20
15
10
10
12
5
0
Rosiglitazone Metformin Glibenclamide
** Patients self-reporting (unconfirmed) hypoglycaemia
Riddle et al. Diabetes Care 2003;26:3080; Kahn et al (ADOPT). NEJM 2006;355:2427–43
Slide No 4
‫הטיפול הקיים אינו מצליח לעצור את הידרדרות הסוכרת‬
UKPDS
Conventional*
Glibenclamide
Metformin
Insulin
Rosiglitazone
Metformin
Glibenclamide
ADOPT
9
8.0
Median HbA1c (%)
8.5
7.5
8
7.5
Rosiglitazone vs Metformin
–0.13 (–0.22 to –0.05), p=0.002
Rosiglitazone vs Glibenclamide
–0.42 (–0.50 to –0.33), p<0.001
7.0
7
Recommended
treatment
target <7.0%†
6.5
6
6.5
6.2% – upper limit of normal range
0
2
4
6
8
Years from randomisation
10
6.0
0
1
2
3
Time (years)
*Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L
†ADA clinical practice recommendations. UKPDS 34, n=1704
UKPDS 34. Lancet 1998:352:854–65; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43
4
5
Slide No 5
12
WC
10
AC
IA
10-year age-adjusted mortality from
CHD according to blood glucose at
baseline
Males
8
% mortality (CHD)
Δ systolic blood pressure (mmHg)
‫הטיפול הקיים אינו מצליח לעצור את העלייה בלחץ דם‬
‫והתמותה ממחלות הלב‬
6
4
2
0
-2
-4
3 6 9
3 6 9
238
221
246
239
220
257
2196
1962
Females
10
3 6 9
Years of diabetes
2437
20
Control
Borderline
(no diabetes) diabetes
Patient numbers
Mean (bars) and 99% CIs (vertical lines) for cross-sectional changes;
WC, white Caucasian; AC, Afro-Caribbean; IA, Asian of Indian origin
Davis et al. Diabetes Care 2001;24:1167–74; Jarrett et al. Diabetologia 1982;22(2):79–84.
Diabetes
‫ – בעל השפעה ישירה על מנגנונים‬GLP 1 ‫ההורמון הטבעי‬
‫פיזיולוגיים רבים בגוף האדם‬
Pancreas
Brain
Insulin secretion
(glucose-dependent)
and beta-cell
sensitivity
Energy intake*
Insulin synthesis
Glucagon secretion
(glucose-dependent)
Beta-cell mass*
*in animal studies
Liver
Hepatic glucose
output
GI tract
Decreased
motility
Liraglutide is a once-daily, human
GLP-1 analogue
Native human GLP-1
C-16 fatty acid
(palmitoyl)
7
9
His Ala Glu Gly Thr Phe Thr Ser Asp
Val
Enzymatic degradation
by DPP-4
7
Liraglutide
9
His Ala Glu Gly Thr Phe Thr Ser Asp
Val
Ser
Glu
Lys Ala Ala Gln Gly Glu Leu Tyr Ser
Glu
36
Phe
Ile Ala Trp Leu Val Arg Gly Arg Gly
Ser
Lys Ala Ala Gln Gly Glu Leu Tyr Ser
Glu
36
Phe
Ile Ala Trp Leu Val Lys Gly Arg Gly
T½=1.5–2.1 min
97% amino acid homology to human GLP-1;
Improved PK: albumin binding through
acylation; heptamer formation
• Slow absorption from subcutis
• Resistant to DPP-4
• Long plasma half-life (T½=13 h)
Knudsen et al. J Med Chem 2000;43:1664–9; Degn et al. Diabetes 2004;53:1187–94
Slide No 8
Change in body weight (kg)
‫ בעל השפעה מובהקת ומשמעותית בהורדת משקל‬GLP1
2
• Waist circumference
1
was reduced from
baseline by 2.7 cm
(1.06 inches) with
liraglutide (p<0.0001)
0
-1
-2
• Waist circumference
-3
-4
Liraglutide
Liraglutide
Glimepiride
1.2 mg
1.8 mg
+ metformin
+ metformin* + metformin*
*p≤0.01 vs glimepiride + metformin
Nauck et al. Diabetes 2008; 57 (Suppl. 1): Abstract 504-P
increased by 0.3 cm
(0.12 inches) with
glimepiride