Presentation on theme: "Insulin initiation made safer and simpler"— Presentation transcript:
1Insulin initiation made safer and simpler (Premix analogue)Insulin initiation made safer and simplerCan somebody read this out?Yes, this is our positioning for NovoMix 30
2Simple convenient meal-time regimen (Premix analogue)Simple convenient meal-time regimen24-hour better physiological controlHigh safetyOnce-a-day dosing with OADs gives superior controlFlexPen – Patient and prescriber acceptanceNovoMix 30 Vs. Glargine: New dataOnce daily NovoMix 30 with OADs: New studyHigh safety: 4 yr dataI want someone to read out these 5 benefits of NovoMix 30. Please qualify each benefit with “NovoMix 30 offers…..”(As the person reads out elaborate on what studies you’ll present. Use superlatives while describing the studies. For example…… what you’ll see here are the best of the scientifc papers. The studies are conducted by the best-known diabetologists in the world. They are conducted according to the best study designs. They are published in the best of the diabetes journals. ….. and it is all about the best of the insulins, NovoMix 30 to be sold by the sales team of the most admired company in India)
3Simple convenient meal-time regimen 3 studies (Premix analogue)Simple convenient meal-time regimen3 studies24-hour better physiological controlHigh safetyOnce-a-day dosing with OADs gives superior controlFlexPen – Patient and prescriber acceptanceHere we go.First benefit.
4NovoMix ® 30 can be given pre- or post-meal (1) (Premix analogue)Study 112-wk, crossover, N=92 (elderly) T2DM20406080100120140160180200Beforebreakfastdinner2 hrs afterBlood glucose levels (mg/dl)n = 91p = NS in all casesPreprandial dosing (NovoMix® 30, bid)Postprandial dosing (NovoMix® 30, bid)Similar BG, given pre- or post mealBlood glucose levels (mg/dl):Preprandial dosing Postprandial dosing(NovoMix® 30, bid) (NovoMix® 30, bid)Before Breakfast 139 ± ± 55Dinner 143 ± ± 652 hrs after Breakfast 159 ± ± 61Dinner 143 ± ± 59Plasma glucose profiles during test meals were also similar:AUC 0-240min ± vs ± mg/dL/min-1There was no difference in the number of hypoglycaemic episodes for either treatment group (47 vs 55 episodes during pre- vs. postprandial treatment periods, respectively; p=ns)Warren et al. Diabetes Res Clin Pract Oct;66(1):23- 9
5NovoMix ® 30 can be given pre- or post-meal (2) Study 2Open-label, crossover trial, N=31, T2DMHuman Mixtard® 30(t = –15 min)6Human Mixtard® 30(t = 0 min)NovoMix® 30(t = 0 min)4NovoMix® 30( t= +15 min)2Blood glucose (mmol/l)Postprandial dosingAUC and glucose Cmax analysis showed no difference NovoMix® 30 (t=+15min) compared with the two Human Mixtard treatmentsNo major hypoglycaemic episodes were recorded during the trialIncidence of minor hypo’s was comparable between the four treatment groupsNo safety concerns were raised during the trial–2–460120180240300Time (min)Kapitza et al. Diabetic Medicine 2004; 21:500–1
6PPG control better than Human Mixtard ® 30 with- or before meal (Premix analogue)Study 3Randomized, crossover, 3-arm, single dose comparison with Human Mixtard ® 30, T1DM , N=50p <p = 0.0133000Human Mixtard® 30280023%9%NovoMix® 302600Blood glucose excursion 4 h after injection (mmol.min.l-1)24002200Compared with Human Mixtard injected at t = 0, NovoMix® 30 reduced the blood glucose excursion by 23% (p < ). When Human Mixtard was injected 30 minutes before the meal, the reduction was of 9% in favour of NovoMix 30 (p=0.013).2000t = 0t = 0t = –30Injection time in relation to mealHermansen et al. Metabolism 2002;51(7):896–900
7NovoMix® 30 offers simple convenient meal-time regimen – why? (Premix analogue)No waiting period after injectionCan be taken with or after mealNo overflow hypoThis is a summary slide for 1st benefit.
8Simple convenient meal-time regimen (Premix analogue)Simple convenient meal-time regimen 24-hour better physiological control3 studies (vs. Mixtard, Lispro Mix, NPH)High safetyOnce-a-day dosing with OADs gives superior controlFlexPen – Patient and prescriber acceptanceFollow same style as for 1st benefit
924h improved postprandial glucose after 3 months (Premix analogue)12-wk, open-label comparison of NovoMix® 30 bd Vs Mixtard® 30 bdN= 294, T1 and T2 DMNovoMix® 30*p < 0.0512*Human Mixtard® 30Study 1*10**8Blood glucose (mmol/l)EuropeanBIAsp 30study group6Blood glucose concentration was significantly lower after breakfast and dinner, before lunch and at bedtime in the NovoMix® 30 group.Analysis of 8-point blood glucose profiles revealed significantly lower blood glucose concentrations after breakfast and dinner, before lunch and at bedtime in the NovoMix® 30 group.At 12 weeks, values were approximately 1% lower in the NovoMix® group after breakfast and dinner (10.4 versus 11.4 mmol/l in NovoMix® 30 and Human Mixtard 30 groups respectively after breakfast, and 9.22 versus 10.2 mmol/l after dinner; p < 0.05 between groups for breakfast and p < 0.02 for dinner).Before lunch, blood glucose concentrations of 6.64 mmol/l in the NovoMix® 30 group compared favourably with 7.57 mmol/l in the Human Mixtard 30 group (p < 0.02), while at bedtime, concentrations of 8.22 versus 9.10 mmol/l in the NovoMix® 30 and Human Mixtard 30 groups, respectively, again favoured NovoMix® 30 (p < 0.05).At other time points, between-treatment differences did not reach statistical significance. Importantly, mean prandial glucose concentration was significantly lower in the NovoMix® 30 group after 12 weeks (1.66 versus 2.34 mmol/l in NovoMix® 30 and Human Mixtard 30 groups, respectively; p < 0.02).Pre-Post-Pre-Post-Pre-Post-Bedtime0200 hBreakfastLunchDinnerBoehm et al. Diabet Med 2002;19(5):393–9
10NovoMix® 30 produces significantly lower prandial glucose increment than H. Mixtard® 30 (Premix analogue)0.511.522.53p < 0.02 between treatment groupsStudy 130%2.34 mM(mmol/l)Mean prandial glucose increment1.66 mMEuropeanBIAsp 30study groupAt 12 weeks, mean prandial glucose excursion was significantly less (p < 0.02) in the NovoMix 30 group compared with the Human Mixtard 30 group.Postprandial glycaemic control was significantly better with NovoMix® 30 when analysed on the basis of mean prandial blood glucose increment - mean increment (post-meal minus pre-meal blood glucose) over the three meals including lunch, when no insulin was given.After 12 weeks, mean prandial glucose increment was 1.66 ± 0.20 mmol/l in the NovoMix® 30 group versus 2.34 ± 0.19 mmol/l for Human Mixtard 30 (p < 0.02).After three months treatment, levels of HbA1c did not differ between the two treatment groups.Only subjects who had a complete set of values for each of the 8-point blood glucose time points were included in the analysis.NovoMix® 30Human Mixtard® 30(n = 128)(n = 141)Boehm et al. Diabet Med 2002;19(5):393–399
11Blood glucose excursion NovoMix® 30 produces significantly lower prandial glucose increment than Lispro MixRandomized, crossover, 3-arm, single dose comparison with Lispro Mix and Human Mixtard® , T2DM , N=45p < 0.001Study 221–17%p < 0.05(mmol/l h)20–10%190– 5h181716In this randomised, cross-over single-dose trial 61 type 2 diabetic patients were exposed on 3 separate study days to the following treatments in random order:NovoMix 30, Humalog Mix 25, and Human Mixtard 30, the latter injected 15 minutes before a standard breakfast (0.4 U/kg for all three insulins). No intermediate or long-acting insulin or OHAs were allowed for the 24 hours preceding the trial days. Mean pre-test FPG levels were similar for all 3 groups ( mmol/L).The PPG excursion over 5 hours was reduced for NovoMix 30 by 10% compared with Mix25, and by 17% compared with Human Mixtard 30.EXC0-5(glu) (mmol/l h) for the different treatment groups were: Humalog Mix 25 – NovoMix 30 – Human Mixtard 30 – 20.1Blood glucose excursion151413Humalog® Mix 25TMNovoMix® 30Human Mixtard® 30Hermansen K et al. Diabetes Care 2002;25:883–8
12Greater HbA1c reduction with NovoMix® 30 vs. NPH (Premix analogue)16-wk, double-blind, parallel comparison of NovoMix® 30 bd Vs NPH bdN= 403, T2 DMNovoMix® 30NPHStudy 30.0-0.2-0.4Change in HbA1c (%)Subjects who had been taking NPH insulin monotherapy before the trial achieved significantly greater reductions in HbA1c when switched to NovoMix® 30 twice-daily compared to those who added another NPH injection (p < 0.005).As expected, subjects who were receiving NPH monotherapy (once- or twice-daily) or who were insulin-naïve prior to the study responded more favourably to both NovoMix® 30 and NPH insulin than those who had been taking combination therapy since they did not discontinue any component of treatment before starting on trial medication.Total population: HbA1c concentration decreased by > 0.6 % (p < versus baseline), in parallel, in both groups; metabolic control continued to improve throughout the trial without reaching a stable level-0.6-0.8p = 0.03-1.0Christiansen et al. Diab Obes Met. 2003; 5(6)
13NovoMix® 30 offers 24-hour better physiological control - Why? (Premix analogue)Significantly lower PG increment than human Mixtard®Significantly reduced HbA1c levelsSummary of benefit 2.
14Simple convenient meal-time regimen (Premix analogue)Simple convenient meal-time regimen 24-hour better physiological control High safety3 studiesOnce-a-day dosing with OADs gives superior controlFlexPen – Patient and prescriber acceptanceFollow same style as before throughout
15Hypo profile as safe as OADs (Premix analogue)16-wk, open-label comparison of NovoMix® 30, NM+Met, Met+SUN=329There were no reports of major hypoglycaemia during the trialLesser number of minor hypoglycaemic episodes with NovoMix® 30NovoMix® 30 + met 23NovoMix® 30 alone 20Met + SUNo other safety concerns were raisedStudy 1Kvapil M et al. Diabetes 2002;51(Suppl 2):A104
16Low risk of nocturnal hypoglycemia (1) (Premix analogue)12-wk, open-label comparison of NovoMix® 30 bd Vs Mixtard® 30 bdN= 294, T1 and T2 DM; RR hypo midnight-6 am = 0.62 (38% reduction)50% relativerisk reductionStudy 245403530hypoglycaemic episodesNumber of42events25EuropeanBIAsp 30study group20Subjects in the NovoMix® 30 group experienced nearly half as many major hypoglycaemic episodes as those in the Human Mixtard 30 group, as well as a trend towards reduced nocturnal hypoglycaemia.1520events105NovoMix® 30Human Mixtard® 30(n = 138)(n = 153)Boehm B et al. Diabet Med 2002;19(5):393–399
17Low risk of nocturnal hypoglycemia (2) (Premix analogue)On correct usage, major hypo can be avoided with NovoMix® 30246810121st year2nd yearYear of studyPatients with at least one majorepisode (%)p = NSp = 0.04Study 3NovoMix® 30Human Mixtard® 3010%2-year extensionofEuropean trialOnly T2DMN=1258%5%This was the continuation of the 3-month study shown before. All analyses shown from this study correspond to the type 2 subgroup (n=125). 95 patients (76%) completed the two year treatment period.The proportion of patients experiencing major hypoglycemia was similar during the first year (NovoMix 30, 5%; Human Mixtard, 8%; NS) but significantly lower with NovoMix 30 than with Human Mixtard during the second (BIAsp, 0%; Human Mixtard, 10%; P = 0.04).Minor episodes were also fewer in the NovoMix 30 group, especially in the second yearFirst treatment year: 265 NovoMix in Human Mixtard 30Second year: 133 NovoMix * Human Mixtad*p < 0.050%Boehm et al. Diabetologia 2001; 44 (Suppl 1): A210.
18NovoMix® 30 offers High safety – Why? (Premix analogue)Hypo profile as safe as OADsReduced risk of between-meal hypoLow risk of nocturnal hypo
19Simple convenient meal-time regimen (Premix analogue)Simple convenient meal-time regimen 24-hour better physiological control High safety Once-a-day dosing with OADs gives superior control2 studies (with Metformin; with glitazone)FlexPen – Patient and prescriber acceptance
20Metformin combination (Premix analogue)US study, 25 centres, N=131, T2 DM, 12 wk3-arm, open-label comparison of Metformin plus once-daily NM, Mixtard, NPHStudy 1Insulin (+metformin)Change in HbA1cfrom baseline (%)NovoMix® 30NPHHuman Mixtard ® 30-3-2.5-2-1.5-1-0.5The total population was divided into sub-groups according to the fasting plasma glucose level (mmol/l). Patients in the 5-8 mg/dl sub-group who were treated with NovoMix 30 had a significantly larger reduction in HbA1c compared with the other two treatment groups (p < vs NPH + met and Human Mixtard 30 + met).Patient numbers:NovoMix® 30 group – n = 12NPH group – n = 23Human Mixtard 30 group – n = 19NovoMix® 30 better glycemic control than Human Mixtard® 30Kilo C et al. J Diabetes Compl 2003; 17:
21Glitazone combination (Premix analogue)N=246, T2 DM OAD failure, 18 wk3-arm, open-label comparison of NM+Pio, NM alone, SU+Pio11.0NovoMix® 30Study 210.5NovoMix® 30 + pioglitazoneGlibenclamide + pioglitazone10.09.5HbA1c (%)**9.08.58.0Replace SU/SU+combn failures with NovoMix® 30+Pio in T2DM7.5*p < 0.017.0ScreeningVisit 6End of TrialRaz I et al. Diabetologia 2003;46(Suppl 2):A8
22NovoMix® 30 offers once-a-day dosing with OADs and gives superior control – Why? (Premix analogue)NovoMix® 30 better glycemic control than Human Mixtard® 30 when combined with OADsReplace SU/SU+combn failures with NovoMix® 30+Pio in T2DM
23Simple convenient meal-time regimen (Premix analogue)Simple convenient meal-time regimen 24-hour better physiological control High safety Once-a-day dosing with OADs gives superior control FlexPen – Patient and prescriber acceptance1 study
24Patient and prescriber acceptance (1) (Premix analogue)N=10282% of healthcare professionals preferred FlexPen® compared to two other prefilled pens2Study 1%p<0.01 vs. Lilly pen and Aventis pen82%14%3%FlexPen®Lilly penAventis prefilled penLawton et al. Diabetes 2001; 50 (suppl 2): A440
25How can you say that NovoMix® 30 FlexPen enjoys patient and prescriber acceptance? (Premix analogue)Studies have shown that > 80% healthcare professionals preferred NovoMix FlexPen
26Patient profile for NovoMix® 30 (Premix analogue)Patient profile for NovoMix® 30
27NovoMix 30: What are the patient profiles? NM30 is suitable for following 3 sets of pts.Elderly (50 yrs) people with type 2 diabetesUncontrolled diabetes in people on conventional insulinsPeople with diabetes prone to or with fear of hypoglycemiaThis is a summary slide stating the obvious.Clearly we have the ideal tool for safer and simpler early insulin initation in NovoMix 30.Having built our case for NovoMix 30, let us move on to the details of each of the specific benefits of NovoMix 30.(Move on to NovoMix 30 slide set)
28How to use NovoMix® 30? Initiation of NovoMix® 30: 0.2 U/kg/24 h (Premix analogue)Initiation of NovoMix® 30:0.2 U/kg/24 hSplit 2/3 morning, 1/3 eveningKeep OAD dose unchangedSwitching from Human Mixtard 30 or NPH: Dose 1:1
29NovoMix 30: Kinetics Human Mixtard ® 30 within 30 minutes 2-8 hours Onset of actionPeak actionDuration of actionWe included this because traditionally we have provided such tables with all our insulins. It was missed out in the medical backgrounders we supplied.
31NovoMix 30 vs. Insulin Glargine (1) NM30 provides both basal & prandial control (Glargine provides only basal control- controlling PPG is important)NM 30 - mitogenicity similar to HI; Glargine – 8-fold increased mitogenicityRetinopathy seen in some patients with type 2 diabetes in studies of 1 year or shorterBerger M. Lancet 2000;356:2013-42 studies presented at ADA ‘04 -NovoMix 30 is superior to GlargineINITIATE studyLuzio et al. study
32NovoMix 30 vs. Insulin Glargine (2) INITIATE study INITIATE = INITiation of Insulin to reach A1c TargEtTwice daily NovoMix 30 vs. Bedtime Insulin GlargineStudy highlightsUS multicentre, randomized,n=233 type 2 DM inadequately controlled on OADDuration= 28 wk.OAD: Pts discontinued SUs, Stabilized on metIf on glitazones, continued on PioRaskin et al. Diabetes June 2004; 53 (Suppl. 2): A143
33NovoMix 30 vs. Insulin Glargine (3) NovoMix 30 is superior to Insulin GlargineBetter overall control - lower HbA1cBetter PPG controlMore patients achieved target HbA1C of ≤ 6.5% or <7%
34NovoMix 30 vs. insulin Glargine (4) Better PPG control than Glargine 2 amBedtimeLunch +90Before lunchBefore dinnerDinner +90Breakfast +90Before breakfastRaskin et al. Diabetes June 2004; 53 (Suppl. 2): A143
35NovoMix 30 Vs. Insulin Glargine (5) More patients achieved target A1C with NM30p=0.000266%p=0.035642%40%Patients reaching targetat week 28 (%)28%HbA1c targetRaskin et al. Diabetes June 2004; 53 (Suppl. 2): A143
36NovoMix 30 vs. Insulin Glargine (6) Luzio et al. Compared PK & PD of NM 30 vs. Glargine28% greater pl. insulin (AUC) % greater glucose-lowering effect400NovoMix® 30PI AUC0-24h; p<0.01350Glargine300250Plasma Insulin (pM)20015010050-149141924Time (h)NovoMix® 30 or glargineNovoMix® 30Luzio et al. Diabetes June 2004; 53 (Suppl 2): A136
37NovoMix 30 Vs. Insulin Glargine (7) Luzio et al. Although equivalent doses of NM30 & Glargine were given:28% greater plasma insulin (AUC) with NovoMix® 30In contrast to Glargine that targets only basal control, NM targets clinically important PPG + good basal control32% greater glucose-lowering effect with NovoMix® 30
39NovoMix: Once daily when initiated, enabled 42% to achieve target HbA1c (1) Jain et al.; presented at ADA ‘04Phase 1 of 48 wk, multicenter trialSubjects not achieving targets on OAD with or without once daily basal insulin (NPH/Glargine)of the 92 patients, at 16 wks23% (21) achieved A1C ≤ 6.5%42% (39) achieved A1C < 7%For subjects who achieved A1C ≤ 6.5%, mean A1C reduction was 2.4%HbA1cBaselineAt 16 wks8.5%6.1%2.4%Jain et al. Diabetes June 2004; 53(Suppl. 2): A130
40NovoMix: Once daily when initiated, enabled 42% to achieve target HbA1c (2) 23% patients reached HbA1c ≤6.5% with NovoMix® 30 ODHbA1c ≤6.5%57% (n=53)20% (n=18)23% (n=21)HbA1c ≥7%42%<7% includes both patients who achieved <6.5% & <7%6.5% < HbA1c <7%Jain et al. Diabetes June 2004;53( Suppl. 2):A130
42NovoMix 30: High safety (4 yr data)- (1) Extension of 3 m European BIAsp 30 study; n=73 with type 2; 4 yr data on safety vs. Mixtard 303 findingsSignificantly less no. of hypoglycaemic episodesNo major nocturnal episode with NM 30 (6 episodes with Mixtard 30)Confirms - with proper use of NovoMix 30, nocturnal hypoglycaemia can be avoidedHypoglycaemiaNovoMix 30Mixtard 30At least 1 major episode411Major Nocturnal6Minor Nocturnal5Boehm et al. Diabetologia 2003; 46(Suppl 2):A269
43NovoMix 30: High safety (4 yr data)- (2) No major nocturnal episode with NM 3024681012Major EpisodesMinor episodes4 years of studyNumber of Nocturnal Episodesp = 0.02p = 0.155 events11events>50%6 eventsBoehm B et al. Diabetologia 2003; 46(Suppl 2):A269
44Simple convenient meal-time regimen (3 studies) Comparison of pre & post meal (elderly) (Warren or Albery et al.)Pre & post meal vs. Mixtard (at or 15 min before meal) (Kapitza et al)Mixtard (at or 30 min before meal) (Hermansen et al. 2002)24-hour better physiological controlvs. Mixtard (Boehm et al slides)vs. Lispro Mix & Mixtard (Hermansen et al. 2002)vs. NPH (Christiansen et al. 2003)
45High safety (3 studies)as safe as OADs (Kvapil et al)Low risk of nocturnal hypoBoehm et al (12 wk study)Boehm et al. (2 yr study)Once-a-day dosing with OADs gives superior control (2 studies)Metformin combination (Kilo et al. 2003)Glitazone combination (Raz et al. 2003)FlexPen – Patient and prescriber acceptance (1 study)Lawton et al.
46Insulin initiation made safer and simpler (Premix analogue)Insulin initiation made safer and simpler(Move on to NovoRapid….)