EASD/ADA 2015 Highlights- insulin. Dr Jarl Hellman

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1 EASD/ADA 2015 Highlights- insulin Dr Jarl Hellman

2 Innehåll NPH Epidemiologi Nya insuliner Basinsulinets bäste vän exklusive hund och UKPDS?

3 G.B Bolli Hypoglykemi - NPH

5 Exogenous insulin and risk of all-cause mortality in type 2 diabetes: a dose-response association C.J. Currie, Cardiff, UK

6 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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16 Switching basal insulin treatment to insulin degludec in patients with type 1 diabetes having an unsatisfactory HbA 1c Lena Landstedt-Hallin, MD, PhD

17 Status Aug. 31, 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

(individualized) 11 did not attend the follow-up 6 switched back to their previous treatment within

18 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

In 238 patients (so far) it has been possible to retrieve a later HbA 1c Median time to this

19 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

nocturnal hypoglycemias In this subgroup of patients with type 1 diabetes, insulin degludec

20 Improved postprandial glycaemic control with faster-acting insulin aspart in patients with type 1 diabetes using CSII in pumps Bruce Bode

21 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: Structure of faster aspart 1 21

22 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:

23 Baseline adjusted plasma glucose (mmol/l) Faster aspart improves postprandial glucose following a standardised meal test 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 Insulin aspart LSMean Diff [95% CI] 0.50 [ 1.07; 0.07] 9.0 [ 19.3; 1.27] p value Nominal time (min) PG av,0 2h (mmol/l) (mg/dl) PG 1h (mmol/l) (mg/dl) PG 2h (mmol/l) (mg/dl) [ 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] 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

24 Significantly lower duration of low IG with faster aspart vs. insulin aspart over 14 days Low IG <2.5 mmol/l [<45 mg/dl]) 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]) [ 0.38; 0.06] P=0.148 Low IG <3.5 mmol/l [<63 mg/dl]) * [ 0.55; 0.01] P=0.039 Low IG 3.9 mmol/l [ 70 mg/dl]) ** [ 0.72; 0.11] P= 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

25 Toujeo vs Lantus Duration upp mot 36h Becker et al. Diabetes Care 2015;38:

26 Ritzel et al ADA 2015 Metaanalys Toujeo vs Lantus Ritzel et al. Diabetes Obes Metab Sep;17(9):859-67

27 Metaanalys Toujeo vs Lantus Ritzel et al. Diabetes Obes Metab Sep;17(9):859-67

28 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

29 Insulin peglispro har en hydrodynamisk storlek liknande albumin Halveringstid 2-3 dygn Effektduration > 36 tim LY : ~ 80 kda (functional) Functionally Larger > Albumin: ~65 kda. PEG= polyethylen glykol kedja

30 Insulin peglispro vs Lantus - HbA1c

31 Insulin peglispro vs Lantus Nattliga hypoglykemier

32 Insulin peglispro vs Lantus Hypoglykemier dagtid

33 Insulin peglispro vs Lantus - Leverfett ON HOLD!

35 L Czupryniak Lodz, Polen

36 Professor Stephen Gough Oxford, UK

39 Tack för mig!

Insulin therapy in various type 1 diabetes patients workshop

Insulin therapy in various type 1 diabetes patients workshop Bruce H.R. Wolffenbuttel, MD PhD Dept of Endocrinology, UMC Groningen website: www.umcg.net & www.gmed.nl Twitter: @bhrw Case no. 1 Male of