BIAsp30 A 1 chieve Tehran 31 July 2015

BIAsp30 A 1 chieve Tehran 31 July 2015

Beginning insulin with biphasic insulin aspart 30: experience from the A 1 chieve study Professor Philip Home Newcastle University

Presenter and sponsor duality of interest Duality of interest Philip Home, for himself or institutions with which he is associated, receives funding from all major insulin manufacturers including Novo Nordisk for his research, educational and advisory activities Role of sponsor Novo Nordisk, was involved in the design, data acquisition, and data analysis of the study, and funded the investigators to provide data from consented people with diabetes. Novo Nordisk is the developer and manufacturer of the insulins studied Acknowledgements We are grateful to all the investigators and people with diabetes who gave time and energy to this study

A 1 chieve biphasic aspart results: insulin naive Key messages In routine care, beginning biphasic insulin aspart 30 (BIAsp30) is associated with very good improvements in glucose control Such improvements are not associated with problems of weight gain or exacerbation of hypoglycaemia Health economic modelling, incorporating the findings and quality of life data, show very good cost-effectiveness

A 1 chieve biphasic aspart results: insulin naive Presentation structure and attributions Study design and rationale Population characteristics Results: biphasic insulin aspart 30 biomedical measures quality of life special groups Health economics Regional, other insulins, and predictor papers not included

A 1 chieve biphasic aspart results: insulin naive Presentation structure and attributions Study design and rationale Population characteristics Results: biphasic insulin aspart 30 biomedical measures quality All data of life are taken from special groups Health economics Home et al, Diabetes Res Clin Pract, 2011 (core findings) Shah et al, Diabetes Res Clin Pract, 2011 (QoL findings) Shah et al, Diabetes Tech Therapeutics, 2013 (BIAsp30 naive) Khamseh et al, Diabetes Ther, 2013 (older adults) Shafie et al, Diabetes Res Clin Pract, 2014 (health economics)

Why perform observational studies? Randomized controlled trials (RCTs) are performed in selected study populations well-motivated participants selected countries RCTs are intensive and closely monitored expensive to perform small populations Observational studies aim to characterize what happens in routine clinical care more typical populations wide geographical recruitment large numbers as less expensive per head

Why perform observational studies? Randomized controlled trials (RCTs) are performed in selected study populations Limitations of observational studies well-motivated participants selected countries Selection of investigators and sites RCTs are intensive will and vary closely by site monitored and region expensive Limited to perform therapy choice small populations Results are associative not causative Observational studies aim to characterize what happens in routine clinical care more typical populations wide geographical recruitment large numbers as less expensive per head

A 1 chieve study overview and design Observational study of people with T2DM (n=66 726) starting insulin analogues in routine clinical practice Global (non-western) recruitment 28 countries 3166 sites Non-interventional Insulin chosen by investigator n=1138 n=14 976 n=4039 n=3074 n=22 447 n=11 020 n=10 032 Other clinical care, measurements, and insulins provided as in routine clinical practice

A 1 chieve study overview and design Observational study of people with T2DM starting insulin analogues in routine clinical practice Insulin naïve or Insulin users Start a study insulin BIAsp30 Insulin detemir Insulin aspart BASELINE Week 0 INTERIM Week 12 FINAL Week 24

A 1 chieve study overview and design Observational study of people with T2DM starting insulin analogues in routine clinical practice Insulin naïve or Insulin users Start a study insulin BIAsp30 Insulin detemir Insulin aspart BASELINE Week 0 INTERIM Week 12 FINAL Week 24 Study objectives Primary: number of attributed adverse drug reactions Secondary: other safety and effectiveness measures Population (biphasic insulin aspart 30, insulin naive) Sex 58% male, age 53.0 (SD 11.5) yr, BMI (kg/m 2 ) 26.1 (4.2), duration of diabetes 6.2 (5.2) yr, time on oral agents 5.4 (4.9) yr

A 1 chieve: participant distribution by pre-study therapy and allocated insulin Insulin ± OGLD 32.8% Pre-study therapy No therapy 9.0% Basal+aspart 6.2% Study therapy Aspart 5.9% Others 3.2% OGLD alone 58.2% Detemir 23.3% Biphasic aspart 30 61.4% Insulin naïve to biphasic aspart 30: n=27 549 (41 %) OGLD, oral glucose-lowering drug

A 1 chieve: change in HbA 1c overall Pre-study therapy Global None OGLDs only Insulin Baseline: 9.5 10.0 9.5 9.4 n: 44661 3075 27294 14292 ΔHbA 1c (%) Data is change, Data is baseline change, to baseline 24 weeks. to 24 All weeks changes p<0.001 All changes p<0.001

A 1 chieve: change in HbA 1c overall and by pre-study therapy group Pre-study therapy Global None OGLDs only Insulin Baseline: 9.5 10.0 9.5 9.4 n: 44661 3075 27294 14292 ΔHbA 1c (%) OGLD, oral glucose-lowering drug Data is change, baseline to 24 weeks. All changes p<0.001

A 1 chieve: HbA 1c results for biphasic aspart 30 HbA 1c (%) HbA 1c (%) 10.0 9.0 9.5 HbA 1c (%) insulin naïve 8.0 7.0 6.0 0 insulin dose (U/day) 33 baseline 24 weeks 7.3

A 1 chieve: SMPG results for biphasic aspart 30 Plasma glucose (mmol/l) 15.0 HbA 1c (%) pre-breakfast insulin naïve post-breakfast 15.6 (281) Plasma glucose (mg/dl) 270 13.0 5.8 ( 104) 240 11.0 11.1 (200) 210 9.0 7.0 baseline 4.0 ( 72) 7.1 (128) 24 weeks baseline 9.8 (176) 24 weeks 180 150 120

A 1 chieve: SMPG results for biphasic aspart 30 Plasma glucose (mmol/l) 15.0 HbA 1c (%) pre-breakfast insulin naïve post-breakfast 15.6 (281) Plasma glucose (mg/dl) 270 13.0 5.8 ( 104) 240 11.0 11.1 (200) 210 9.0 7.0 baseline 4.0 ( 72) 7.1 (128) 24 weeks baseline 9.8 (176) 24 weeks 180 150 120

A 1 chieve: Hypoglycaemia with biphasic aspart 30 Events/ person-yr HbA 1c (%) 2.5 2.0 insulin naïve Data collected in the last 4 weeks before visits 1.5 1.0 1.0 9.5 HbA 1c (%) 7.3 1.1 0.5 baseline 24 weeks

A 1 chieve: weight change with biphasic aspart 30 ΔWeight (kg) 1.0 0.5 HbA 1c (%) insulin naïve 70.5 0.0 70.2-0.5 9.5 HbA 1c (%) 7.3-1.0 baseline 24 weeks

A 1 chieve: HbA 1c and hypoglycaemia according to age group with biphasic aspart 30 Age (years) 40 >40 65 >65 HbA 1c baseline (%) 9.6 (1.8) 9.5 (1.6) 9.5 (1.9) change (%-units) -2.4 (1.8) -2.1 (1.6) -2.2 (1.8) Hypoglycaemia people (%) people (%) 3.0 4.1 6.1 event/person-year 0.71 1.02 1.49

A 1 chieve: change in EQ-5D visual analogue score biphasic aspart Best imaginable health 100 90 80 70 60 50 40 30 20 10 0 (%) Worst imaginable health

A 1 chieve: change in EQ-5D visual analogue score biphasic aspart insulin naïve 24 weeks Baseline Best imaginable health 100 90 80 70 60 50 40 30 20 10 0 (%) Worst imaginable health

A 1 chieve: change in EQ-5D visual analogue score components: biphasic aspart 100 Participants with 75 problem (%) 50 Mobility Self-care Usual Pain Anxiety activity discomfort depression 25 0 Baseline 24 weeks

A 1 chieve: lipid levels and systolic BP at baseline and 24 weeks on biphasic aspart Lipid levels (mmol/l) Baseline 24 weeks Systolic BP (mmhg) LDL cholesterol Triglyceride HDL cholesterol

A 1 chieve: health economic analysis for biphasic aspart 30 in insulin-naïve people Saudi Arabia India Indonesia N Africa 30-year ICER (cost per QALY gained) US dollar 550 370 1632 1955 GDP fraction 0.03 0.25 0.47 0.46 1-year ICER (cost per QALY gained) US dollar 1690 635 4206 3095 GDP fraction 0.08 0.43 1.20 0.73 ICER, incremental cost-effectiveness ratio; QALY, quality adjusted life year Data analysis by CORE diabetes model Cost-effective USD <30 000, highly cost-effective <10 000 Cost-effective GDP fraction <3.0, highly cost-effective <1.0 (WHO)

A 1 chieve: overall summary for biphasic aspart 30 In insulin naïve people in poor blood glucose control starting biphasic insulin aspart : Blood glucose control measured as HbA 1c, FPG or PPPG improved markedly clinically & statistically significantly This was not accompanied by an increase in reported hypoglycaemia, or in body weight Useful and safe improvements in blood glucose control were seen in: all age groups and all global regions Systolic blood pressure and health-related quality of life were also improved to a clinically useful extent The intervention was highly cost-effective in a range of countries

A 1 chieve BIAsp 30: comment and interpretation The results suggest that in routine clinical practice biphasic insulin aspart 30 can deliver the gains seen in clinical trials The lack of weight gain despite marked improvement in HbA 1c, and the improvement in blood pressure, suggest that starting insulin analogues can be an opportunity for enhanced lifestyle behaviours The lack of increase in hypoglycaemia despite marked improvement in HbA 1c also suggests improved self-management The cost-effectiveness data suggests wide implementation is desirable

A 1 chieve BIAsp30: conclusion Globally, in routine clinical practice, starting biphasic insulin aspart is an opportunity, in insulin naïve people in poor metabolic control, to improve their cardiovascular risk profile and health-related quality of life without detriment to safety or excess cost

A 1 chieve BIAsp30: conclusion Globally, in routine clinical practice, starting biphasic insulin aspart is an opportunity, in insulin naïve people in poor metabolic control, to improve their cardiovascular risk profile and health-related quality of life without detriment to safety or excess cost Thank you for your attention, and to all the participants and investigators in Iran who contributed to the study

Thank you for your attention