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What to do when basal bolus therapy fails in Type 2 Diabetes

What to do when basal bolus therapy fails in Type 2 Diabetes. [insert name]. Prescribing information can be found on the last slide. This meeting has been developed and sponsored by. UKPDS: A 1% decrease in HbA 1c is associated with a reduction in complications.

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What to do when basal bolus therapy fails in Type 2 Diabetes

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  1. What to do when basal bolus therapy fails in Type 2 Diabetes [insert name] UKHMG00596a February 2012 Prescribing information can be found on the last slide

  2. This meeting has been developed and sponsored by UKHMG00596a February 2012

  3. UKPDS: A 1% decrease in HbA1cis associated with a reduction in complications Microvascular complications e.g. Renal disease and blindness* 37% Amputation or fatal peripheral vascular disease* 43% HbA1c1% 21% Deaths related to diabetes* 14% Myocardial infarction* *P<0.0001; ** P=0.035. UKPDS=United Kingdom Prospective Diabetes Study. Cerebrovascular event** 12% UKHMG00596a February 2012 Stratton IM et al (2000) BMJ321: 405–12

  4. Beta-cell dysfunction – a core defect in type 2 diabetes Beta-cell dysfunction Insulin resistance Type 2 diabetes + = Impaired ability to secrete insulin and compensate for insulin resistance UKHMG00596a February 2012 Del Prato S, Marchetti P (2004) Diabetes TechnolTher6: 719–31 • Genetic and environmental pathophysiology • One of the two core defects in type 2 diabetes • Therapeutic strategies should ideally target both defects

  5. Insulin and glucose patterns: Basal vs. mealtime hyperglycaemia in type 2 diabetes Diagram shows 24-hour plasma glycaemic pattern typical of healthy people (lower border of grey area) and those with mild non-insulin dependent diabetes mellitus (upper border of grey area). Red area shows part of the glycaemic abnormality of diabetes accounted for by excessive postprandial hyperglycaemia, whereas grey area shows part due to elevated basal glycaemia. 15.0 12.5 10.0 Plasma glucose concentration (mmol/L) 7.5 5.0 2.5 0 0600 1200 1800 0000 0600 Time of day (hours) UKHMG00596a February 2012 Adapted from Riddle MC (1990) Diabetes Care 13: 676–86

  6. As people with diabetes get closer to HbA1c targets, the need to manage postprandial glucose (PPG) increases 100 Fasting Plasma Glucose Postprandial Glucose 70% Relative contribution (%) 50 30% 0 <7.3 >10.2 10.2―9.3 9.2―8.5 8.4―7.3 HbA1c (%) quintiles Adapted from Monnier L et al (2003) Diabetes Care 26: 881–5 UKHMG00596a February 2012

  7. There are several ways of addressing PPG and FPG with insulin FPG=fasting plasma glucose; PPG=postprandial glucose. UKHMG00596a February 2012 Basal–bolus insulin therapy Premixed insulin therapy (with various ratios of longer- and shorter-acting insulin components)

  8. In Non-diabetic Individuals, Basal Secretion Represents Approximately 50% Total Daily Insulin When the basal insulin secretion rate was extrapolated over a 24-h period and expressed as a percentage of the total 24-h insulin secretion, basal secretion represented 50.1±3.1% of the total 24-h insulin secretion in normal subjects and 45.2±2.2% in obese patients. 600 500 400 Percent Basal Insulin Secretion 300 200 Normal Obese 100 0 0600 1000 1400 1800 2200 0200 0600 Clock Time (hours) Polonsky KS et al. (1988) J ClinInvest; 81:442-48 UKHMG00596a February 2012

  9. Patients With Type 2 Diabetes on Intensive Insulin Therapy Regimens Use 50% Basal and 50% Bolus Insulin Multiple Daily Injection (n=50) After titrating doses throughout the study each group independently had a regimen that consisted of approx 50% basal and 50% preprandial insulin Continuous Subcutaneous Insulin Infusion (n=48) % Total Daily Insulin Dose Basal Dose Bolus Dose Doses adjusted to achieve target preprandial and bedtime BG levels UKHMG00596a February 2012 Herman WH et al. (2005) Diabetes Care; 28:1568-73

  10. Is basal–bolus always the gold standard? *This was a multinational, 52-week, open-label, parallel-group, non-inferiority, treat-to-target trial, designed to compare the efficacy and safety profiles of detemir and glargine as the basal insulin component of a basal–bolus regimen in people with type 2 diabetes. Insulin aspart was used as the bolus insulin. The intention-to-treat population included 319 participants. • Donnelly LA et al (2007) Q J Med 100: 345–50 • Hollander P et al (2008) ClinTher30: 1976–87 UKHMG00596a February 2012 High injection frequency can lead to poor adherence, causing inadequate glycaemic control1 Many people with type 2 diabetes on basal–bolus therapy have suboptimal glycaemic control. In one large study*, almost two thirds of people failed to achieve HbA1c<7% (<53 mmol/mol)2

  11. Currently available human and analogue premixed insulins Higher proportion of rapid-acting insulin component provides greater activity in the postprandial period. UKHMG00596a February 2012

  12. “Mid-mix” analogue insulins: Clinical data UKHMG00596a February 2012

  13. Switching from twice-daily premixed insulin 30/70 or 25/75 to premixed insulin 50/50 After switching to biphasic insulin lispro 50/50 Before switching to biphasic insulin lispro 50/50* 12.5 10 Switching to twice-daily Mix 50/50 insulin injections controlled post-prandial blood glucose levels and stabilized diurnal blood glucose variations in patients with type 2 diabetes mellitus who had poor glucose control on insulin 70/30 or 75/25 n=13 7.5 Change in blood glucose from FBG (mmol/L) 5 ** * 2.5 * 0 –2.5 FBG AB BL AL BS AS Bedtime *Participants were receiving biphasic insulin aspart 30/70 (30% aspart, 70% aspartprotamine), biphasic human insulin 30/70 (30% rapid-acting insulin, 70% NPH), or biphasic insulin lispro 25/75 (25% lispro, 75% lisproprotamine) AB=after breakfast; AL=after lunch; AS=after supper; BL=before lunch; BS=before supper; FBG=fasting blood glucose; NPH=neutral protamineHagedorn. *P<0.05; **P<0.01. UKHMG00596a February 2012 Tanaka M, Ishii H (2010) J Int Med Res 38: 674–80

  14. Comparison of thrice-daily biphasic insulin aspart 70/30, thrice-daily biphasic insulin aspart 50/50, and twice-daily biphasic insulin aspart 30/70 Reduction in mean HbA1c (%) at 36 weeks of treatment, intent-to-treat population 70/30 (30/70)*** 50/50 (30/70)** Biphasic insulin aspart 30/70* 0 Glycaemic control improved with thrice-daily biphasic insulin aspart 50/50 without higher incidence of hypoglycaemia compared with twice-daily insulin aspart 30/70 8.9 8.8 8.9 −0.5 Reduction in HbA1c (%) −1 7.3 −1.5 7.2 NS 7.0 −0.30% (P=0.0004) −2 *Participants received twice-daily biphasic insulin aspart 30/70 (30% aspart, 70% aspartprotamine) throughout the study (ITT=200); **Participants received thrice-daily biphasic insulin aspart 50/50 (50% aspart, 50% aspartprotamine) throughout the study (ITT=114), or switched their dinner insulin to biphasic insulin aspart 30/70 at 12 weeks (ITT=87); ***Participants received thrice-daily biphasic insulin aspart 70/30 (70% aspart, 30% aspartprotamine) throughout the study (ITT=91), or switched their dinner insulin to biphasic insulin aspart 30/70 at 12 weeks (ITT=107). All regimens were in combination of metformin. NS=not significant; ITT=intent-to-treat. UKHMG00596a February 2012 Cucinotta D et al (2009) Diabetes ObesMetab11: 700–8

  15. Thrice-daily biphasic insulin lispro 50/50 was non-inferior to basal–bolus therapy In people with type 2 diabetes uncontrolled on insulin glargine or lispro mix 25/75 (25% lispro, 75% lisproprotamine): a non-inferiority intensification substudy of the DURABLE trial Biphasic insulin lispro 50/50 (n=174) Basal–bolus therapy* (n=171) P=0.990 P=0.566 P=0.660 9 8 7 HbA1c remained stable in both treatment groups 6 HbA1c (%) 5 4 3 2 1 0 3 6 Baseline DURABLE=assessing durability of basal versus lispro mix 25/75 insulin efficacy. *Glargine plus mealtime insulin lispro. Time (months) UKHMG00596a February 2012 Miser WF et al (2010) ClinTher32: 896–908

  16. Thrice-daily biphasic insulin aspartwas non-inferior to basal–bolus therapy Biphasic insulin aspart* (n=196) Basal–bolus therapy** (n=198) 10 9 HbA1c decreased from 9.1±0.7% to 7.8±1% in both treatment groups 8 7 HbA1c (%) 6 5 4 0 0 2 4 6 8 10 12 14 16 Time (week) * BMI≤30 kg/m2: biphasic insulin aspart 70/30 (70% aspart, 30% aspartprotamine) at breakfast and lunch and biphasic insulin aspart 30/70 (30% aspart, 70% aspartprotamine) at supper; BMI>30 kg/m2: biphasic insulin aspart 50/50 (50% aspart, 50% aspartprotamine) at breakfast and lunch and biphasic insulin aspart 30/70 (30% aspart, 70% aspartprotamine) at supper; ** NPH plus mealtime aspart. BMI=body mass index; NPH=neutral protamineHagedorn. UKHMG00596a February 2012 Ligthelm RJ et al (2006) Exp ClinEndocrinol Diabetes 114: 511–9

  17. Twice-daily biphasic insulin lispro 50/50 vs. basal–bolus therapy: Glycaemic control Biphasic insulin lispro 50/50 (n=14) 14 Basal–bolus therapy* (n=14) 13 12 Both the premix group and basal bolus group showed significant reduction in HbA1c over the 12 weeks 11 10 9 HbA1c (%) 8 7 6 5 4 Time (months) 0 At entry 1 2 3 *NPH plus mealtime insulin lispro. NPH=neutral protamineHagedorn. Participants were insulin-naïve people with type 2 diabetes who had suboptimal glycaemic control on maximal doses of oral antidiabetes drugs. Masuda H et al (2008) Diabetes ObesMetab10: 1261–5 UKHMG00596a February 2012

  18. Twice-daily biphasic insulin lispro 50/50 vs. basal–bolus therapy: Insulin therapy-related quality of life questionnaire scores ** Score These results might suggest that twice-daily injections of premixed rapid-acting insulin analogue therapy could achieve good glycaemic control and better QOL compared with BB therapy in insulin-naıve type 2 diabetes. *** ** ** ** *NPH plus mealtime insulin lispro. **P≤0.05; ***P=NS. NPH=neutral protamineHagedorn; NS=not significant. UKHMG00596a February2012 Masuda H et al (2008) Diabetes ObesMetab10: 1261–5

  19. Advantages of TDS“mid-mix” premixed insulins UKHMG00596a February2012 A thrice-daily “mid-mix” regimen comprehensively addresses the postprandial glucose peaks associated with the three main meals Compared with a basal–bolus regimen, a thrice-daily “mid-mix” regimen may be simpler to teach, and the single delivery device may benefit people who find it difficult to cope with the demands of frequent injections, glucose monitoring and necessary dose adjustments

  20. Summary UKHMG00596a February2012 • As people with type 2 diabetes get closer to HbA1c targets, the significance of postprandial hyperglycaemiaincreases • Biphasic insulin lispro 50/50 is an appropriate option to consider in a selected group of individuals

  21. Practical factors to consider when changing a patient’s insulin regimen [insert name] UKHMG00596a February2012

  22. Some practical factors to consider when changing a patient’s insulin regimen The factors that determine a patient’s regimen will be individual and vary from patient to patient UKHMG00596a February2012

  23. Basal–bolus therapy: How you might identify patients as uncontrolled UKHMG00596a February2012 • Potential signs and clues to look for: • Erratic blood glucose control • Missing injections • Not adjusting doses • People who appear to not be engaged or who are frustrated

  24. Basal–bolus therapy: How you might identify patients as uncontrolled UKHMG00596a February2012 • Potentially people who might fall into this category: • Those who are unable to dose adjust • Those who are not carbohydrate aware • Those who have problems with frequency of injections • Those who have problems grasping the concept of basal bolus

  25. UKHMG00596a February2012 How many of your patients with type 2 diabetes on a basal bolus regimen adjust their insulin based on the amount of carbohydrate they eat?

  26. Premixed insulin • Why might a premix offer an advantage? • Some people may find it a simpler regimen than basal–bolus therapy • Fewer injections • There can be less self-monitoring of blood glucose required • In some cases only one type of insulin and device is used • In some patients it can be less time consuming to teach than basal bolus UKHMG00596a February2012

  27. Premixed insulin UKHMG00596a February2012 • Potentially people who are likely to benefit from this therapy: • Those who are unable or not wanting to adjust insulin doses / carbohydrate count • Those who prefer fewer injections

  28. Premixed insulin UKHMG00596a January 2012 • Some of the perceived limitations: • In some patients it is a less flexible regimen – regular meals and a “structured” lifestyle required • There might be the potential to need to “feed” insulin • In some patients it might be more difficult to correct for high blood glucose levels

  29. UKHMG00596a February2012 No panacea – need to discuss and tailor the insulin regimen to the individual

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