EASD/ADA 2015 Highlights- insulin Dr Jarl Hellman
Innehåll NPH Epidemiologi Nya insuliner Basinsulinets bäste vän exklusive hund och UKPDS?
G.B Bolli Hypoglykemi - NPH
Exogenous insulin and risk of all-cause mortality in type 2 diabetes: a dose-response association C.J. Currie, Cardiff, UK
Data from a 10% sample of the UK population Identified 8,414 people exposed to insulin-only regimen Conclusion: There was a dose-response association between insulin and the risk of death in subjects with type 2 diabetes. Those progressing to insulin therapy in older age and with good glucose control were at particularly high risk. Bästa HbA1c här kring 58 mmol/mol (7,5% DCCT)..
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Switching basal insulin treatment to insulin degludec in patients with type 1 diabetes having an unsatisfactory HbA 1c Lena Landstedt-Hallin, MD, PhD
Status Aug. 31, 2015 527 patients have switched to insulin degludec 344 had HbA 1c above their goal (individualized) 11 did not attend the follow-up 6 switched back to their previous treatment within weeks 4 moved and were lost to follow-up 1 died from pneumonia and sepsis Data on 333 patients followed-up will be presented 65% on basal b.i.d. 35% had problems with hypoglycemia L. Landstedt-Hallin EASD 2015
Results Was the initial HbA 1c improvement due to e.g. increased self-monitoring when switching to a new insulin? In 238 patients (so far) it has been possible to retrieve a later HbA 1c Median time to this HbA 1c 53 weeks [IQR 50-59] Baseline: 74.8 [14.2] 9.0 % At 21 weeks: 70.0 [14.2] 8.6 % L. Landstedt-Hallin EASD 2015 At 53 weeks: 69.0 [12.6] 8.5 % L. Landstedt-Hallin
Conclusion In a real-world follow-up of patients with type 1 diabetes and unsatisfactory HbA 1c, switching to insulin degludec improved HbA 1c despite lower insulin doses with a lower risk for nocturnal hypoglycemias In this subgroup of patients with type 1 diabetes, insulin degludec appears to be clinically useful as a new tool for basal insulinization L. Landstedt-Hallin EASD 2015
Improved postprandial glycaemic control with faster-acting insulin aspart in patients with type 1 diabetes using CSII in pumps Bruce Bode
Faster aspart is a new formulation of insulin aspart Niacinamide * : absorption modifier Responsible for fast absorption Asp Asp Arginine: stability enhancer Improves stability Zn 2+ Stabilises the insulin hexamer *Niacinamide is also known as nicotinamide 1. Adapted from Brange J et al. Diabetes Care 1990; 13: 923 54. Structure of faster aspart 1 21
Insulin action (at meal time)* The need for ultra fast-acting insulin analogues Ultra fast-acting insulin Rapid-acting insulin Rapid-acting Ultra fast-acting insulin insulin analogues: should: Better approach physiological insulin Were a major step forward in secretion in T1D optimising Replace early the insulin management secretion in T2D of PPG 1 Have an improved profile for use in pumps Simplified practical aspects (eg, IMI and snacking) Regular human insulin Time (h) *Schematic representations. IMI, injection-meal interval; PPG, postprandial glucose. 1. Mudaliar SR et al. Diabetes Care 1999; 22: 1501 6. 22
Baseline adjusted plasma glucose (mmol/l) Faster aspart improves postprandial glucose following a standardised meal test 8 6 4 Meal test PG profiles for faster aspart vs. insulin aspart Faster aspart Insulin aspart Meal test PG profiles for faster aspart vs. insulin aspart PG av,0 1h (mmol/l) (mg/dl) Faster aspart LSMean 1.89 34.0 Insulin aspart LSMean 2.39 43.0 Diff [95% CI] 0.50 [ 1.07; 0.07] 9.0 [ 19.3; 1.27] p value 0.084 2 0 2 60 0 60 120 180 240 Nominal time (min) PG av,0 2h (mmol/l) (mg/dl) PG 1h (mmol/l) (mg/dl) PG 2h (mmol/l) (mg/dl) 3.03 54.5 10.05 180.9 11.71 210.8 4.02 72.4 11.68 210.6 12.93 232.7 0.99 [ 1.95; 0.03] 17.8 [ 35.1; 0.54] 1.64 [ 2.79; 0.48] 29.5 [ 50.2; 8.6] 1.22 [ 2.98; 0.53] 22.0 [ 53.6; 9.5] 0.044 0.006 0.168 Significantly greater glucose-lowering effect with faster aspart vs. insulin aspart during the first 2 h after a standardised meal test PG av,0 2h was calculated as AUC PG,0-2h /2h PG Pre-dose where AUC PG,0-2h was the area under the plasma glucose concentration time profile based on observed values and actual measurement times in relation to time of injection between 0 and 2 hours. CSII, continuous subcutaneous insulin infusion; PG, plasma glucose. 23
Significantly lower duration of low IG with faster aspart vs. insulin aspart over 14 days Low IG <2.5 mmol/l [<45 mg/dl]) 0.6 0.7 Faster aspart Insulin aspart Treatment difference [95% CI] 0.05 [ 0.22; 0.12] P value P=0.557 Low IG <3.0 mmol/l [<54 mg/dl]) 1.0 1.2 0.16 [ 0.38; 0.06] P=0.148 Low IG <3.5 mmol/l [<63 mg/dl]) 1.5 1.8 0.28* [ 0.55; 0.01] P=0.039 Low IG 3.9 mmol/l [ 70 mg/dl]) 2.0 2.5 0.42** [ 0.72; 0.11] P=0.008 0.00 0.01 0.02 0.03 Duration of low interstitial glucose per 24 h (h) *P<0.05; **P<0.01. LS mean values were obtained by a mixed model with treatment and period as fixed and subject as a random effect; corresponding 95% CIs were derived from this model. 24
Toujeo vs Lantus Duration upp mot 36h Becker et al. Diabetes Care 2015;38:637 643
Ritzel et al ADA 2015 Metaanalys Toujeo vs Lantus Ritzel et al. Diabetes Obes Metab. 2015 Sep;17(9):859-67
Metaanalys Toujeo vs Lantus Ritzel et al. Diabetes Obes Metab. 2015 Sep;17(9):859-67
Patient-level meta-analysis of 1-year phase 3a EDITION T2DM studies: glycaemic control and hypoglycaemia with insulin glargine 300 U/ml (Gla-300) vs glargine 100 U/ml (Gla-100) Ritzel et al. EASD 2015, 975-P
Insulin peglispro har en hydrodynamisk storlek liknande albumin Halveringstid 2-3 dygn Effektduration > 36 tim LY2605541: ~ 80 kda (functional) Functionally Larger > Albumin: ~65 kda. PEG= polyethylen glykol kedja
Insulin peglispro vs Lantus - HbA1c
Insulin peglispro vs Lantus Nattliga hypoglykemier
Insulin peglispro vs Lantus Hypoglykemier dagtid
Insulin peglispro vs Lantus - Leverfett ON HOLD!
L Czupryniak Lodz, Polen
Professor Stephen Gough Oxford, UK
Tack för mig!