Insulin intensification : the usage of premixed insulin after basal fails

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Insulin intensification : the usage of premixed insulin after basal fails
EDDY SUPRIADI, MD | MARZOEKI MAHDI , MD. HOSPITAL.BOGOR

Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013

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  • Premix insulin is recommended by IDF T2DM treatment algorithm at insulin start and intensification
  • Slide is animated. The six categories will appear one by one
  • Studies such as the United Kingdom Prospective Diabetes Study have demonstrated the importance of achieving and maintaining glycaemic targets in order to minimise the long-term adverse complications associated with diabetes.1
  • Addressing PPG is essential to achieve HbA1c targets and the contribution of PPG to overall hyperglycaemia increases as HbA1c levels are reduced.
  • Addessing PPG is an important aspect of diabetes treatment as patients spend around 50% of their day in a post-prandial state.1
  • By combining 70% protaminated intermediate-acting insulin aspart with 30% insulin aspart, NovoMix® 30 more closely approximates the physiologic basal and meal-related insulin response observed in healthy individuals compared with basal insulin.
  • Values are mean (± SD) Information on pre-study therapy was missing for 88 patients(values represent only those patients with baseline and final visit data).
  • Switching patients from a basal insulin analogue to NovoMix® 30 does not result in increased rates of major or minor hypoglycaemia as this data from the IMPROVE™ study demonstrates.1
  • A1chieve® is a 24-week, international, prospective, multicentre, non-interventional, observational study of people with T2D who had begun using basal insulin detemir (Levemir1, Novo Nordisk, Denmark), bolus insulin aspart (NovoRapid1, Novo Nordisk) and biphasic insulin aspart 30 (NovoMix1 30, Novo Nordisk), alone or in combination, to evaluate their clinical safety and effectiveness in routine clinical use outside the Western economies [23]. The study was carried out in 3166 centres in 28 countries across Asia, Africa, Latin America and Europe, grouped into seven geographical regions: China; South Asia (Bangladesh, India, Pakistan); East Asia (Indonesia, Korea, Malaysia, Philippines, Singapore, Taiwan); north Africa (Algeria, Morocco, Tunisia, Libya); Middle East/Gulf (Egypt, Iran, Jordan, Turkey, Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, UAE, Yemen); Latin America (Argentina, Mexico) and Russia. Participants were recruited between January 2009 and June 2010.
  • Animated slide.
  • Speaker should mention that starting with basal/bolus therapy is not recommended to GPs
  • This slide is animated
  • Practical guideline for swiching from basal insulin OD or BID to BIAsp 30 BID (breakfast and dinner)1:1 Total dose transfer to BIAsp 30Split the dose 50:50 prebreakfast and predinnerTitrate the dose preferably once a weekDiscontinue sulfonylureas (SUs)Continue metforminConsider discontinuing TZDs as per local guideline and practiceAdminister BIAsp 30 just before meals
  • Insulin intensification : the usage of premixed insulin after basal fails

    1. 1. Slide no 1 Riwayat Hidup : • • • • • Nama : Dr Eddy Supriadi, Sp.PD, FINASIM Tempat/ Tgl. Lahir : Jakarta, 19 Feb 1968 Pendidikan : Dokter, FKUI 1993, Penyakit Dalam FKUI 2006 Tempat Kerja : RS Dr H. MARZOEKI MAHDI KOTA BOGOR Pengalaman : - Inspire Diabetes Program. PERKENI Indonesia-STENO Denmark. Jakarta 2013. - Workshop and Symposium on the Diabetic Foot. Noordwijkerhout, The Netherlands, 2011 - dll.
    2. 2. Insulin intensification : the usage of premixed insulin after basal fails EDDY SUPRIADI, MD. MARZOEKI MAHDI , MD. HOSPITAL. BOGOR
    3. 3. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple ? • Conclusion
    4. 4. Background • Type 2 diabetes progression is characterised by a decline in ß-cell function and worsening insulin resistance1 • Within 1 year, the majority of basal insulin patients will need another insulin to reach target2 The ADA/EASD have found that basal plus two or more bolus injections is a highly complex regimen3 • Premix Insulin offer a simple intensification of one insulin in one device4 1. Fonseca. Br J Diab Vasc Dis 2008;8(Suppl 2):S3; 2. Holman et al. N Engl J Med 2007;357:1716–30; 3. Inzucchi et al. Diabetologia 2012;55:1577–96.. 4. Garber AJ, et al. Diabetes, Obesity and Metabolism, 8, 2006, 58–66 4
    5. 5. Slide 5 Type 2 diabetes is a progressive disease HOMA: homeostasis model assessment Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58)
    6. 6. ADA/EASD Position on Sequential Insulin Strategy in Type 2 Diabetes Non-Insulin Regimes Number of Injections Regimen Complexity Basal Insulin Only Usually with OAD 1 Low 2 Mod. +3 High Basal Insulin + 1 mealtime rapid-acting injection Pre-mixed Insulin twice-daily Basal Insulin + >2 mealtime rapid-acting injection More Flexible Less Flexible Less Convenient More Convenient Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin aspart 30/70. Int J Clin Pract 2009 Flexibility Convenience*
    7. 7. 7 IDF recommends premix or basal insulin at start and intensification Lifestyle measures If not at target (generally HbA1c <7%) First line Second line Third line: insulin start Fourth line: insulin intensification • Metformin • Sulphonylurea • Premix insulin • Premix insulin • • • • Standard approach Alternative approach • Sulphonylurea • a-glucosidase inhibitor • Metformin • a-glucosidase inhibitor • DPP-4 inhibitor • Thiazolidinedione Basal insulin • Basal insulin a-glucosidase inhibitor • Basal-bolus insulin DPP-4 inhibitor Thiazolidinedione • GLP-1 agonist 1. Adapted from the IDF Treatment algorithm for people with type 2 diabetes. Accessed at: http://www.idf.org/treatment-algorithm-people-type-2-diabetes (accessed May 2012) APROM ID# 5069 approval date: May 2013 treatments that can help to address PPG are included at every stage of the IDF treatment algorithm1
    8. 8. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple ? • Conclusion
    9. 9. Treatment therapies for Type 2 diabetes: Achieving HbA1c < 7% Premixed Insulin Lifestyle + Metformin +-other OAD or GLP-1 agonists Basal Insulin (Once-daily treat-totarget) HbA1c ≥7.0% (Twice daily Treat to target) Basal Insulin (Basal + 3 prandial) Basal Insulin (Basal + 1 or 2 prandial) HbA1c ≥7.0%, FPG on target, PPG ≥160 mg/dl Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.
    10. 10. 10 Every 1% drop in HbA1c can reduce long-term diabetes complications1 14% 37% 21% Myocardial infarction* Microvascular complications* *p<0.0001. 1. Adapted from Stratton et al. BMJ 2000;321:405–12 (UKPDS 35) Deaths related to diabetes*
    11. 11. Slide 11 The benefits of good blood glucose control are clear Myocardial infarction Good control is ≤ 7.0% HbA1c HbA1c measures the average blood glucose level over the last three months -14% HbA1c -1% Microvascular complications -37% Deaths related to diabetes -21% Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412.
    12. 12. Yet good glycaemic control is not achieved HbA1c (%) 10.0 12.4% have HbA1c>10.0 % 9.5 9.0 20.2% have HbA1c>9.0 % 8.5 8.0 64.2% of patients with type 2 diabetes have HbA1c≥7.0 % 37.2% have HbA1c>8.0 % 7.5 7.0 6.5 6.0 5.5 Adapted from Unger et al. Am J Med 2008;121:S3–S8.
    13. 13. 13 Relative contribution to overall hyperglycaemia (%) PPG control is vital to achieving HbA1c targets1 100 80 PPG has an 60 40 20 0 <7.3 7.3–8.4 8.5–9.2 9.3–10.2 HbA1c quintiles FPG PPG 1. Adapted from Monnier et al. Diabetes Care 2003;26:881–5 APROM ID# 5069 approval date: May 2013 >10.2 to overall hyperglycaemia as patients approach HbA1c targets1
    14. 14. 14 Patients spend 50% of their day in the postprandial state1 MIDNIGHT Evening meal 4h Fasting state 6 PM 6 AM Postprandial state 4h Breakfast Lunch MID-DAY 1. Adapted from Monnier. Eur J Clin Invest 2000;30(Suppl. 2):3–11 4h
    15. 15. Is postprandial hyperglycaemia harmful? IDF Recommendation: Postprandial hyperglycaemia is harmful, and should be addressed • Postprandial hyperglycaemia are independent risk factors for macrovascular disease • Postprandial hyperglycaemia is associated with: • Increased risk of retinopathy, increased CIMT, decreased myocardial blood volume/blood flow, increased risk of cancer, impaired cognitive function in the elderly • Postprandial hyperglycaemia causes oxidative stress, inflammation and endothelial dysfunction
    16. 16. 16 The dual-release insulin concept: Premix Insulin targets both FPG and PPG1 Physiological insulin profile: Basal component Basal insulin Meal-related peaks BiAsp 30 Plasma insulin level • • Physiological insulin profile Time Adapted from Garber2 1. Garber et al. Diabetes Obes Metab 2006;8:58–66; 2. Garber et al. Diabetes Obes Metab 2007;9:630–9 APROM ID# 5069 approval date: May 2013
    17. 17. 17 The IMPROVE™ study - reduced FPG and PPG with BiAsp 301 1 Blood glucose (mmol/L) 1 14 12 10 8 6 4 2 0 12.6 10.9 7.9 6.6 Pre-breakfast FPG Post-dinner PPG Baseline Week 26 *p<0.001 1. Adapted from Valensi et al. Int J Clin Pract 2009;63:522–31 APROM ID# 5069 approval date: May 2013 FPG and PPG from baseline at Week 26 following initiation or switch to BiAsp 301
    18. 18. INITiation of Insulin to reach A1c TargEt (INITIATE): BIAsp 30 (BID) vs. glargine (OD) Insulin glargine OD (12 U, bedtime) + metformin ± pioglitazone n=233 Type 2 diabetes BMI <40 kg/m2 Body weight <125 kg HbA1c >8% on metformin ± TZD BIAsp 30, pre-breakfast (6 U) and pre-dinner (6 U) + metformin ± pioglitazone 4-week run-in: Stop insulin secretagogues (SUs, nateglinide, repaglinide) and -glucosidase inhibitors (acarbose) Optimise metformin to ≥1500 mg/day Switch rosiglitazone for 30 mg pioglitazone –4 0 28 Time (weeks) Raskin et al. Diabetes Care 2005;28(2):260–5 SUs, sulphonylureas
    19. 19. INITIATE: significantly more patients met HbA1c targets with BIAsp 30 BIAsp 30 (n=100) Insulin glargine (n=109) Patients reaching target at Week 28 (%) p=0.0002 70 60 50 40 30 20 10 0 p=0.0356 66% 42% 40% 28% HbA1c <7.0% (ADA goal) HbA1c ≤6.5% (ACE and IDF goal) HbA1c target Raskin et al. Diabetes Care 2005;28(2):260–5
    20. 20. Difference in prandial glucose increment between treatments (mmol/L) INITIATE: improved control of PPG with BIAsp 30 ns 0.66 1.0 *p<0.05 **p<0.01 Favours glargine 0.5 0.0 –0.5 –1.0 –1.5 –2.0 –2.5 –1.17 ** –1.25 * Breakfast Lunch Dinner Raskin et al. Diabetes Care 2005;28(2):260–5 –0.59 * Favours BIAsp 30 Total mean prandial glucose increment ns, not significant
    21. 21. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple ? • Conclusion
    22. 22. 22 A well-documented tolerability profile 2002–2012 In at least 68 BiAsp 30 RCTs* 2007–10 PRESENT observational study1–3 >22,000 patients 2008–2012 IMPROVE™ observational study4–6 >51,000 patients 2010–2012 A1chieve® observational study7,8 >66,000 patients BiAsp 30 tolerability profile demonstrated over of clinical experience*1–8 * PubMed search using term ‘biphasic insulin aspart’ and the limit ‘randomised controlled trial’. 1. Sharma et al. Curr Med Res Opin 2008;24:645–52; 2. Almustafa et al. Diabetes Res Clin Pract 2008;81(Suppl. 1):S10–5; 3. Güler et al. Arch Drug Inf 2009;2:23–33; 4. Valensi et al. Int J Clin Pract 2009;63:522–31; 5. Wenying et al. Curr Med Res Opin 2009;25:2643–54; 6. Gumprecht et al. Int J Clin Pract 2009;63:966–72; 7. Home et al. Diabetes Res Clin Pract 2011;94:352–63; 8. El Naggar et al. Diabetes Res Clin Pract 2012;98:408–13
    23. 23. 23 Events/patient year Hypoglycaemia following intensification from basal insulin analogue to BiAsp 301 10 7.8 8 6.1 6 4 2 0 0.197 0.016 Major Minor Hypoglycaemia Baseline Final visit 1. Adapted from Gumprecht et al. Int J Clin Pract 2009;62:1809–19 APROM ID# 5069 approval date: May 2013 in the rate of hypoglycaemia following intensification to BiAsp 301
    24. 24. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple ? • Conclusion
    25. 25. Presentation title Role of observational studies and RCTs Observational studies . . . " . . . complement (the data) from RCTs by providing an insight into how treatments perform in day-to-day practice in more clinically representative patient populations ” Home, Diabetes Res Clin Pract, 2010 Date Slide no 26
    26. 26. Presentation title Date Strengths of observational studies      1. Yang et al Diabetes Res Clin Pract, 2010 2. Home Diabetes Res Clin Pract, 2010 3. Dreyer et al Health Affairs 2010 Slide no 27
    27. 27. A1chieve study overview and design • Observational study of people with T2DM in routine clinical practice Start a study insulin • Biphasic insulin aspart 30 • Insulin detemir • Insulin aspart BASELINE Week 0 • INTERIM Week 12 FINAL Week 24 Study objectives • Primary: number of attributed adverse drug reactions (includes major hypoglycaemia) • Secondary: other safety and effectiveness measures
    28. 28. BiAsp 30± OAD: Indonesia efficacy results Insulin users HbA1c (%) FPG (mg/dl) Baseline values 10.0 9.4 232 204 n 385 92 769 383 Change from baseline to week 24 0,0 PPG (mg/dl) 303 752 278 328 -10 -30 -1,0 -50 -70 -90 -2,0 -2.1* -110 -130 -3,0 -150 *p<0.001 -72* -110*
    29. 29. BiAsp 30± OAD: Baseline 24 weeks Indonesia hypoglycaemia results Overall Insulin users No. of pt w/hypo 29 Major Nocturnal Insulin users 1 0 Insulin users 0 16 0 Events/patientyear 3.0 2.0 1.64 1.0 0.51 0.0 0.03 0.00 0.00 0.00
    30. 30. A1chieve: Self-rated health in insulin users (BiAsp 30) Best imaginable health Patients on BiAsp 30 100 Baseline 90 80 70 60 24 weeks BiAsp 30: real world improvement in patients quality of life 50 40 30 20 Worst imaginable health 10 0 Baseline 24 weeks
    31. 31. A1chieve study overall summary • Significant HbA1c, FPG and PPG reductions for BiAsp • 2.1% HbA1c reduction in insulin users • Indonesian patients reported a reduction in hypoglycaemia during treatment with BiAsp at 24 weeks in term of: • Minor • Major • Nocturnal • Patient quality of life increased significantly with BiAsp following 24 weeks of treatment
    32. 32. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple? • Conclusion
    33. 33. How do we define insulin intensification? INITIATE OPTIMISE INTENSIFY Starting insulin therapy Dose titration to ensure that the patient receives the maximum benefit from the prescribed treatment Modification of the insulin regimen, e.g. adding to or changing the therapy in order to maintain glycaemic control
    34. 34. Slide 35 Basic Insulin Start Recommendation If Fasting Blood Glucose is elevated If both Fasting and Prandial Blood Glucose are elevated Source: ADA Guidelines • • • • Start with Basal Insulin Start with Premix Insulin OR add Basal Insulin to OAD OR Start Basal/Bolus Therapy
    35. 35. Insulin Treatment Optimization How to Optimize Treatment with Pre-mix Basal Once-Daily Usually with OAD Start with basal 10u / day and titrate accordingly if glycemic target is not reached. Source: PERKENI Insulin Guidelines 2011 Pre-mix Twice-Daily Usually with OAD Switch to Pre-mix twice-daily if glycemic target is not reached. Initially keep the dose equal from basal but split it in half and inject at morning and dinner time. If high blood glucose before evening meal increase morning dose of premix and if high fasting Blood glucose increase evening dose pre-mix. Pre-mix Thrice-Daily Usually with OAD Switch to Pre-mix thricedaily if glycemic target is not reached. Add 2-6 unit or 10% of daily dose to the total dose and inject at lunch. Reduce morning dose with 2-4 units after staring lunch time injections
    36. 36. Practical guideline on intensification of insulin therapy with BIAsp 30 A simple algorithm for the intensification of basal insulin OD or BiD to BIAsp 30 BID Basal insulin OD or BID HbA1c 7-8% FPG >110 mg/dl Titrate basal insulin to achieve FPG <110 mg/dl 1. Adapted from Unnikrishnan et al. Int J Clin Pract 2009;63:1571–7 HbA1c >8% FPG: 73-110 mg/dl Switch to BIAsp 30 BID
    37. 37. 38 Intensifying basal insulin patients to Premix is simple In basal insulin patients: start with the same total daily dose1 • BiAsp 30 can be intensified to three-times daily* to achieve glycaemic control2 • The morning dose can be split into morning and lunchtime doses for threetimes-daily dosing3 • BIAsp 30 TID: alternative to basal-bolus (fewer daily injection and only one device need) Intensify to unit basal insulin unit BiAsp 30 Breakfast Split total daily dose 50% Dinner 50% Twice daily BiAsp 30 Adapted from Unnikrishan1 *Guideline for the recommended dose adjustment included in the NovoMix® 30 SmPC3. 1. Unnikrishnan et al. Int J of Clin Prac 2009; 63:1571–7; 2. Garber et al. Diabetes Obes Metab 2006;8:58–66; 3. Novo Nordisk. NovoMix® 30 summary of product characteristics
    38. 38. 39 Adjusting the dose of BiAsp 30 Recommended dose adjustments Pre-meal blood glucose level BiAsp 30 dose adjustment mg/dL Units <80 80–110 111–140 141–180 >180 -2 0 +2 +4 +6 Adapted from NovoMix® 30 SmPC1 1. Novo Nordisk. NovoMix® 30 summary of product characteristics. May 2012
    39. 39. Outlines Presentation structure • What recent guideline say • Addresing post prandial glucose excursion • Minimising hypoglycaemia • A1chieve observational study: real life experience including Indonesia • Insulin Intensification : how simple? • Conclusion
    40. 40. Conclusion • Because of the progessiveness of diabetes, Insulin regimen and dosage needs to be monitored and intensified • BiAsp 30 provides effective glycaemic control with significant HbA1c reduction, FPG and PPG reduction with additional convenience for patients • In Indonesia, in a real life clinical practice, A1chieve study results for BiAsp 30 show significant improvements in overall glycaemic control in terms of HbA1c, FPG and PPG, reductions in hypoglycemia and a significant improvement in patient quality of life
    41. 41. Thank You

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