Ueda2016 symposium - basal plus & basal bolus - lobna el toony
- 2. Stepwise intensification of insulin in T2DM management— Exploring the concept of the basal-plus approach in clinical practice LOBNA F ELTOONY Head Of Internal Medicine Department Faculty Of Medicine Assiut University
- 6. HOMA=homeostasis model assessment Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S21–5. Decreasing -cell function as part of the progression of T2DM Normal -cell function by HOMA (%) Time (years) 0 20 40 60 80 100 ―10 ―8 ―6 ―4 ―2 0 2 4 6 Time of diagnosis? Pancreatic function ~ 50% of normal
- 8. Clinical Inertia: “Failure to Advance Therapy When Recommended” MeanA1CatLastVisit* (%) 8.2 Years ADA Goal Diet and Exercise Years Elapsed Since Initial Diagnosis Initiation of insulin therapy SU or metformin Combination oral agents8.6% 8.9% 9.6% 7 8 9 10 2.5 Years 2.9 Years 2.8 Years *Adapted from: Brown JB et al. Diabetes Care. 2004;27:1535-1540.
- 10. Insulin The most powerful agent we have to control glucose
- 12. Patient J.L., December 15, 1922 February 15, 1923 The Miracle of Insulin
- 13. Indications of insulin Continuous Use * Type 1 Diabetes * Type 2 Diabetes with OHA failure - Primary - Secondary Intermittent Use * Type 2 diabetes during - major surgery - pregnancy, labour and delivery - myocardial infarction - acute infections Life-saving in T1DM Essential in T2DM
- 14. Starting dose of insulin • T1DM: 1 -0.2-1 U/kg / day1 • T2DM: 0.2-0.3 U/kg / day In split mixed regimen- 2/3 as intermediate acting & 1/3 as short- acting 2 In basal bolus regimen: ½ basal at bed time and ½ bolus in 3 divided doses. Dosage is individualized and titrated soon 1Goodman & Gillman’s The pharmacological basis of therapeutics ed. 9th .pg. 1501 2 Harrison’s Principles of Internal Medicine (15th Edition) pg. 2131
- 16. HbA1C(%) UKPDS: Long-term follow-up Bailey CJ & Day C. Br J Diabetes Vasc Dis 2008; 8:242–247. Holman RR, et al. N Engl J Med 2008; 359:1577–1589. Differences in mean glycated hemoglobin levels between the intensive therapy group and the conventional-therapy group were lost by 1 year, with similar glycated hemoglobin improvements thereafter in all groups (p= not significant) P=0.71 Glucose similar BUT CV events now better Metformin group 21% 33% 27%
- 17. A new paradigm Del Prato S. Diabetologia 2009; 52:1219–1226. Del Prato S. Diabetologia 2009; 52:1219–1226.
- 18. Why Early insulin initiation? Clinical & Pharmacological Reasons(4) Insulin Improves beta-cell function (reduces glucotoxicity & lipotoxicity) Reverses insulin resistance Improves Quality of Life Beneficial effects on lipids Insulin provides 4 benefits beyond glycemic control
- 19. LIFESTYLE MEASURES Then at each step, if not to target (generally HbA1c <7.0%) IDF Treatment algorithm for people with type 2 diabetes or oror Metformin Sulfonylurea or α-Glucosidase inhibitor Sulfonylurea α-Glucosidase inhibitor or DPP-4 inhibitor or Thiazolidinedione Basal insulin or Pre-mix insulin GLP-1 agonist Basal + meal-time insulin Metformin (if not first line) α-Glucosidase inhibitor or DPP-4 inhibitor or Thiazolidinedione Basal insulin or Pre-mix insulin (later basal + meal-time) Alternative approachUsual approach Consider first line Consider second line Consider third line Consider fourth line
- 20. Early Insulinization Is Recommended by the ADA/EASD to Avoid Clinical Inertia ●If HbA1c targets are not achieved after ~3 months of initial treatment, alternative therapy such as basal insulin should be initiated1,2 Monotherapy Efficacy* Hypo risk Weight Side effects Costs Metformin High Low risk Neutral / loss GI / lactic acidosis Low If HbA1c target not achieved after ̴3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- and disease-specific factors): Dual therapy† Efficacy Hypo risk Weight Side effects Costs Metformin + Sulfonylurea Thiazolidinedione DPP-4 inhibitor SGLT 2 inhibitor GLP-1 receptor agonist High Moderate risk Gain Hypoglycemia Low High Low risk Gain Edema, HF, fxs Low Intermediate Low risk Neutral Rare High If HbA1c target not achieved after ̴3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- and disease-specific factors): Intermediate Low risk Loss GU, dehydration High High Low risk Loss GI High Insulin (basal) Highest High risk Gain Hypoglycemia Variable Healthy eating, weight control, increased physical activity, and diabetes education Early insulin therapy has the potential to achieve near-normal glucose control & prevent progression of glucose intolerance3 1. Inzucchi SE, et al. Diabetologia 2012;55:1577–96 2. Nathan DM, et al. Diabetes Care 2009;32:193–203 3. ORIGIN Trial Investigators. N Engl J Med 2012;367:319–28 ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes
- 21. AACE/ACE diabetes algorithm for glycemic control (A1c > 9.0%).
- 22. Rationale for initiating insulin therapy with basal insulin
- 23. WHAT!? Did you say INSULIN?! Barriers to the Use of Insulin
- 24. Patient Concerns About Insulin • Fear of injections • Worries that insulin could worsen diabetes • Concerns about hypoglycemia • Complexity of regimens
- 27. Step One: Initiating Insulin • Start with either… – Bedtime intermediate-acting insulin or – Bedtime or morning long-acting insulin Insulin regimens should be designed taking lifestyle and meal schedules into account Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
- 28. Basal insulin in type 2 diabetes (e.g. LA 0.1-0.2 U/kg or 10U) Non-insulin therapies LA = Long-Acting insulin: Glargine, Detemir Basal Insulin in Type 2 Diabetes
- 29. Basal Insulin Therapy • Usual first step in beginning insulin therapy • Continue oral agents and add basal insulin to optimize FPG • A1C of up to 9.0% usually brought to goal (7%) by addition of basal insulin therapy to oral agents • Easy and generally safe: patient-directed treatment algorithms with small risk of serious hypoglycemia ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes. ADA/EASD Management of hyperglycemia in type 2 diabetes: A patient-centered approach. Diabetologia (2012) 55:1577–1596
- 30. Starting With Basal Insulin in DM 2 Advantages • 1 injection with no mixing • Insulin pens for increased acceptance • Slow, safe, and simple titration • Low dosage • Effective improvement in glycemic control • Limited weight gain 6-37
- 32. Comparison of 24-hour glucose levels in control subjects vs patients with diabetes (p<0.001). Adapted from Hirsch I, et al. Clin Diabetes 2005;23:78–86. Time of day (hours) 400 300 200 100 0 06.00 06.0010.00 14.00 18.00 22.00 02.00 Plasmaglucose(mg/dl) Normal Meal Meal Meal 20 15 10 5 0 Plasmaglucose (mmol/l) Why Basal insulin? Hyperglycaemia due to an increase in fasting glucose T2DM Treating fasting hyperglycaemia lowers the entire 24-hour plasma glucose profile
- 33. A balanced approach for insulin therapy in T2DM 250 200 150 100 50 0 Plasmaglucose(mg/dL) 06:00 12:00 18:00 24:00 06:00 Time T2DM Normal Mealtime hyperglycaemia Fasting hyperglycaemia 60 40 20 0 Contribution(%) 80 1 (<7.3) 2 (7.3-8.4) 3 (8.5-9.2) 4 (9.3-10.2) 5 (>10.2) HbA1c quintiles Postmeal hyperglycaemia Fasting hyperglycaemia Diabetes Care 1990; 16: 676–686 Monnier L. Diabetes Care 2003;26:881
- 34. Fix Fasting First Basal Insulins Normal Fasting Blood Glucose Elevated Fasting Hyperglycemia and HGO Hence need to fix fasting first
- 35. Look at all available basal insulins
- 36. Types of basal insulin Intermediate-Acting (e.g. NPH, lente) Long-Acting (e.g. ultralente) Long-Acting Analogues (glargine, detemir) Onset 1-3 hr(s) 3-4 hrs 1.5-3 hrs Peak 5-8 hrs 8-15 hrs No peak with glargine, dose- dependent peak with detemir Duration Up to 18 hrs 22-26 hrs 9-24 hrs (detemir); 20-24 hrs (glargine) Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.
- 37. 37 Profile of Insulin Glargine vs NPH Glargine NPH
- 38. The quest for a better basal insulin… A “qualified A1c” by hypoglycaemia Hypoglycaemia NPH Glargine A1c ~ 0.4–0.6% ? The impact of hypoglycaemia on A1c
- 39. Addition of Glargine allows most patients with T2DM to reach glycemic targets 1Riddle M, et al. Diabetes Care 2003;26:3080–6; 2Yki-Järvinen H, et al. Diabetologia 2006;49:442–51; 3Bretzel RG, et al. Lancet 2008;371:1073–84; 4Janka H, et al. Diabetes Care 2005;28:254–9; 5Rosenstock J, et al. Diabetes Care 2006;29:554–9; 6Yki-Jarvinen H, et al. Diabetes 2006;55 Suppl. 1:A30 HbA1c(%) APOLLO3 LAPTOP4 Triple Therapy5 LANMET2Treat-To- Target1 INITIATE6 7.147.15 6.96 7.14 6.80 8.71 8.85 8.80 9.5 8.808.61 6.96 Baseline Study endpoint 58.0 Target HbA1c ≤7% (%) 49.4 48.057.0NA NA 7 8 9 10 6 The most studied basal insulin With established CV safety, 10 million patients, > 60 million patient-years, >59,000 participants in clinical trials
- 40. Basal Insulin Therapy in T2DM: AACE/ACE Recommendations • Initiate insulin treatment by adding a long-acting basal formulation to existing noninsulin agents 40 Relatively peakless time-action curves Greater day-to-day consistency Lower risk of hypoglycemia • Start with 10 U or 0.1-0.2 U/kg per day at bedtime • Slowly titrate by 1-3 U every 2-3 days until FPG reaches the desired target (<100 mg/dL for most patients) • Decrease dosage if FPG declines below a threshold specified for individual patient *Under FDA review as of October 2012. Rodbard HW, et al. Endocr Pract. 2009;15:540-559. Basal insulin analogues (detemir, degludec,* or glargine) are strongly preferred over human NPH insulin
- 41. Schreiber SA, et al. Diabetes Technol Ther 2008; 10:121–7. Insulin glargine + OADs provides sustained glycaemic control Extension of an original 9-month, open-label, uncontrolled, multi-centre, observational study (n = 12,216) Months of treatment 6.5 7.0 7.5 8.0 8.5 9.0 3 9 32 8.6 7.2 7.0 7.0 MeanHbA1c(%) n = 1,915 (extension) Sustained Glycaemic Control with Basal Insulin in T2DM: ‘Real-life’ Data
- 42. 8.5 9.0 8.0 7.5 7.0 6.5 0 4 8 12 16 20 24 HbA1c(%) NPH + OAD Insulin glargine + OAD Weeks 0 2 4 6 8 10 12 14 16 21% risk reduction p <0.02 42% risk reduction p <0.01 Overall Nocturnal Hypoglycemia Eventsperpatientperyear Insulin Glargine vs. NPH in Treat-to- Target Trial: HbA1c and Hypoglycemia Riddle et al. Diabetes Care 2003;26:3080-6. Randomized to NPH or Glargine + OAD with target HbA1c <7%
- 43. Initiate & Titrate basal insulin FPG, fasting plasma glucose Nathan DM, et al. Diabetes Care 2009;32:193-203. Initiate insulin with a single injection of a basal insulin (Glargine) Check FPG daily In the event of hypoglycemia or FPG level <3.89 mmol/L (<70 mg/dL) Reduce bedtime insulin dose by 4 units, or by 10% if >60 units • Bedtime or morning long-acting insulin OR • Bedtime intermediate-acting insulin Daily dose: 10 units or 0.2 units/kg INITIATE • Increase dose by 2 units every 3 days until FPG (70–130 mg/dL) • If FPG is >180 mg/dL, increase dose by 4 units every 3 days TITRATE Continue regimen and check HbA1c every 3 monthsMONITOR • Continue regimen and check HbA1c every 3 months
- 44. • If HbA1c is <7%... – Continue regimen and check HbA1c every 3 months • If HbA1c is ≥7%... – Move to Step Two… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
- 45. Step-by-step approach Even with optimal use of basal insulin, it is estimated that, using current treatment paradigms, ~40% of people will not meet HbA1c recommendations of < 7%. A well-considered step-by-step approach to the intensification of insulin therapy, adding one, two or three prandial insulin injections to basal insulin according to each individual’s prandial requirements, seems a logical way forward. The current evidence underlying this concept of meal-driven insulin intensification for the treatment of T2D, as well as the implications of adopting such an approach in clinical practice. D. R. Owens Diabet. Med. 30, 276–288 (2013
- 46. In spite of titrating basal insulin, the inability to achieve glycemic control despite normal or near-normal fasting glucose usually means that excessive glycemic excursions may be occurring during postprandial period
- 47. Step Two: Intensifying Insulin If fasting blood glucose levels are in target range but HbA1c ≥7%, check blood glucose before lunch, dinner, and bed and add a second injection: • If pre-lunch blood glucose is out of range, add rapid-acting insulin at breakfast • If pre-dinner blood glucose is out of range, add NPH insulin at breakfast or rapid-acting insulin at lunch • If pre-bed blood glucose is out of range, add rapid-acting insulin at dinner Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
- 48. InsulinEffect B DL HS Bolus insulin Basal insulin Basal-Plus Insulin Therapy Endogenous insulin Adapted with permission from McCall A. In: Insulin Therapy. Leahy J, Cefalu W, eds. New York, NY: Marcel Dekker, Inc; 2002:193 Tuesday, February 16, 2016 48
- 49. Making Adjustments • Can usually begin with ~4 units and adjust by 2 units every 3 days until blood glucose is in range Nathan DM et al. Diabetes Care 2006;29(8):1963-72. •When number of insulin Injections increase from 1- 2………..Stop or taper of insulin secretagogues (sulfonylureas).
- 50. Insulin Initiation & Intensification – AACE 2015 START BASAL A1c <8% A1c >8% TDD: 0.1-0.2U/Kg TDD: 0.2-0.3U/Kg Insulin titration every 2-3 days to reach glycaemic goal Fixed regimen: Increase TDD by 2U Adjustable regimen FBG > 180 mg/dL: add 20% of TDD FBG 140-180 mg/dL: add 10% of TDD FBG 110-139 mg/dL: add 1 unit If hypoglycemia, reduce TDD by BG < 70 mg/dL: 10% - 20% BG < 40 mg/dL: 20% - 40% Glycemic control not at goal* Intensify: Add prandial insulin TDD: 0.3-0.5 U/Kg 50% Basal Analog 50% Prandial Analog Less desirable : NPH & regular/premixed insulin Insulin titration every 2-3 days to reach glycemic goals Increase prandial dose by 10% for any meal if the 2-hr PP or next premeal glucose is > 180 mg/dl Premixed: Increase TDD by 10% if fasting/premeal BG > 180 mg/dL If fasting AM hypoglycemia, reduce basal insulin If nighttime hypoglycemia, reduce basal and/or pre-supper or pre- evening snack short/rapid-acting insulin If between-meal daytime hypoglycemia, reduce previous premeal short/rapid-acting insulin * <7% for most patients with T2DM; fasting & premeal BG < 110 mg/dL; absence of hypoglycemia; ENDOCRINE PRACTICE Vol 21 No. 4 April 2015 e1
- 51. When to stop titrating basal insulin and add prandial insulin? Current opinions 1 Skyler JS. In: Lebovitz HE, ed. Therapy for diabetes Mellitus and related disorders. Alexandria, VA: American Diabetes Association, Inc.; 2004:207- 223. 2 American Diabetes Association. Practical Insulin: A Handbook of Prescribing Providers. 3rd ed. 2011:1-68 The individual is not meeting glycemic targets on basal insulin1-4 and: A1C still not at goal with 0.5 U/kg/day of daily basal insulin3 Elevated A1C despite normal FPG with basal insulin2,3 FPG with basal insulin is within targeted range, but PPG is persistently above goal3,4 Further increases in basal insulin result in hypoglycemia3
- 52. Stepwise Intensification of Treatment for Continuity of Control Progressive deterioration of -cell function Lifestyle changes Oral agents Basal Add basal insulin and titrate Basal plus Add prandial insulin at main meal Basal bolus Additional prandial doses as needed FBG above target HbA1c above target HbA1c above target FBG at target HbA1c above target Adapted from Raccah D et al. Diabetes Obes Metab 2008;10(2):76-82. When glycaemic targets are not met: – Treatment should be changed to the next ‘step’ – Currently, therapy change is often too late – Earlier treatment modification is necessary
- 53. • If HbA1c is <7%... – Continue regimen and check HbA1c every 3 months • If HbA1c is ≥7%... – Move to Step Three… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.
- 54. Advancing Basal/Bolus Insulin Indicated when FBG acceptable but – A1C > 7% or > 6.5% and/or – SMBG before dinner > 140 mg/dL Insulin options – To glargine or NPH, add mealtime aspart / lispro – To suppertime 70/30, add morning 70/30 – Consider insulin pump therapy Oral agent options – Usually stop sulfonylurea – Continue metformin for weight control – Continue glitazone for glycemic stability?
- 56. Isoglycemic clamp study Inadequate prandial insulin : Postprandial Hyperglycemia Excess inter-prandial supply: Increased risk of Hypoglycemia Insulin Profiles: Premixed 30/70 Aspart 0 100 200 300 400 0 4 8 12 16 20 24 hrs PlasmaInsulin(pM) HYPER HYPER HYPER Luzio S et al, Diabetologia 49:1163-8, 2006 risk HYPO risk HYPO The pre-mixes are NOT suitable to Treat-to-target A1C <7.0%
- 57. Insulin Glargine is more suited for initiating insulin therapy than premixed insulin analogues Basal insulin e.g. insulin Glargine Premixed insulin e.g. premixed insulin aspart 30/70 Initial number of injections daily 1 21 Daily initial dose Insulin glargine: 10 U 6 U + 6 U1 Timing of injections Morning or evening Breakfast and dinner1 Monitoring for titration targets FPG (once daily) FBG and preprandial BG (twice daily)1 Lifestyle Flexible mealtimes and meal content Scheduled mealtimes and set meal plans Intensification Addition of once-daily prandial insulin (basal-plus) to basal bolus Increase to 3 times daily 1. Summary of product characteristics for NovoMix 30, 50 and 70. Available at www.emea.europa.eu/humandocs/Humans/EPAR/novomix/novomix.htm (last accessed 2 July 2008).
- 58. Clinical evidence for the ‘basal-plus’ / basal-bolus’ approach
- 59. Glulisine added to glargine further improves glycemic control *For difference in change in HbA1c Randomization Proof of concept (POC) study: Basal Plus+1 therapy versus basal insulin glargine alone Control group Glargine + glulisine p = 0.0499 0 10 20 30 40 %achievingHbA1c<7.0% 8.8 22.4 p = 0.029* Control group Glargine + glulisine 6 7 8 9 HbA1c(%) 8.0 7.87.8 7.5 Endpoint 8.0 7.8 7.8 7.5 8.8 Owens DR, et al. Diabetes Obes and Metab 2011.
- 60. Control group Glargine + glulisine p = ns 0.0 0.2 0.4 0.6 Meanbodyweightchange frombaseline(kg) 0.5 0.2 Proof of concept (POC) study: Basal Plus+1 therapy versus basal insulin glargine alone Glargine + glulisine Control group 0 2 4 6 8 7.68 8.19 10 p = ns Symptomatichypo (event/patient-year) Glargine + glulisine 0.0 Control group 0.0 0.1 0.2 0.3 Severesymptomatichypo (event/patient-year) 0.2 p = ns Basal plus approach is safe with only minor weight gain Randomization Endpoint Owens DR, et al. Diabetes Obes and Metab 2011.
- 61. 1.2.3 study: Insulin glargine with addition of 1, 2 or 3 daily doses of glulisine • Subjects: – Insulin naïve (785 entered study, 343 randomized) with type 2 diabetes (HbA1c ≥8.0%) – Receiving 2 or 3 OHAs for ≥3 months (OHAs continued except sulfonylurea) Randomization (subjects with HbA1c >7.0%, n=434) 24 weeks Insulin glargine (n=785) 14 weeks Additional insulin glulisine once daily (n=115) Additional insulin glulisine twice daily (n=113) Additional insulin glulisine three times daily (n=115) (1.2.3 study) Mean study entry values: • HbA1c (%): 9.8 • BMI (kg/m2): 35.0 Davidson M, et al. Endocr Pract 2011;17:395–403.
- 62. Glargine plus glulisine (patients with HbA1c >7%) Responders (whole population; n=785) 0 20 40 60 80 %achievingHbA1c<7.0% Additional subjects achieved HbA1c <7.0% with glulisine added to glargine 23% Run in Randomization Wk 8 Wk 16 Wk 24 7.40 7.0 10.19 10.19 10.16 7.44 7.29 8.0 9.0 10.0 Glulisine 1x Glulisine 2x Glulisine 3x HbA1c (randomized population; n=343) Glargine (alone) Subjects achieved HbA1c <7.0% with glargine during run in 37% Davidson M, et al. Endocr Pract 2011;17:395–403. HbA1c(%) Intensification with glulisine improves glycemic control 1.2.3 study: Insulin glargine with addition of one, two or three daily doses of glulisine
- 63. p = NS for all other pairwise comparisons Hypoglycemia (event/patient-year) 0 0.25 0.50 0.75 1.0 Severeorserious‘hypos’ x1 x2 x3 Glulisine 0.28 0.89 p = 0.044 0.64 0 5 10 15 20 x1 x2 x3 Glulisine Confirmedsymptomatic‘hypos’ 12.3 10.6 15.9 x1 x2 x3 0 1 2 3 4 5 Meanchangefrombaseline(kg) 3.8 3.9 4.1 Glulisine Body weight Davidson M, et al. Endocr Pract 2011;17:395–403. 1.2.3 study: Insulin glargine with addition of one, two or three daily doses of glulisine
- 64. Randomization if A1c >7.0% Glimepiride stopped Glargine / Premix Other OADs maintained All-To-Target: Study Design Randomized Comparison of Premixed Insulin vs Either Basal-Plus or Basal-Bolus Premix (70/30) 2 x daily + 2-3 OADs N = 192 G+1: Glargine + upto 1 Glulisine + 2-3 OADs N = 189 G+3: Glargine + upto 3 x Glulisine + 2-3 OADs N = 191 Screening * ** * * Treatment in G+1 and G+3 groups intensified at weeks 12, 24, 36 or 48 if A1c>7% Riddle, MC et al. Diabetes, Obesity and Metabolism 2014. 16: 396–402, Inclusion Criteria T2DM≥2 years BMI<45kg/m2 HbA1c>7.5% Use of 2-3 OADS Run-in Run-in (4 week) Randomized (60 weeks) R
- 65. Hypoglycemia (event rate per patient-year) *p < 0.01 vs premix ; **p < 0.001 vs premix 12.2 7.1* 7.2* 1.9 0.8** 0.9** 0.2 0.1* 0.2 Premix BID Basal Plus Basal Bolus Δ HbA1c from baseline (%) All-to-Target: Stepwise intensification with glargine and glulisine vs premix <70 mg/dL + symptoms <50 mg/dL + symptoms <36 mg/dL *p =0.06 vs premix ; **p <0.01 vs premix Mean baseline HbA1c = 9.4% -1.8 -2.1* -2.2** Premix BID Basal Plus Basal Bolus Riddle, MC et al. Diabetes, Obesity and Metabolism 2014. 16: 396–402,
- 66. All-to-Target: A comparison of premixed, basal-plus and stepwise basal-bolus regimens • More patients achieve A1c < 7% using glargine and glulisine in basal-plus and stepwise basal- bolus regimens compared with twice daily premixed insulin Riddle M, et al. Diabetes 2011;60(Suppl.1):PP-0409. HbA1c<7% at week 60 HbA1c<7% at week 60 without hypoglycemia * vs premix 39% 49% 45% 14% 24% 24% 0% 10% 20% 30% 40% 50% 60% %ofpatients(at week60) Premix BID n=192 Glargine+glulisine basal-plus n=189 Glargine+glulisine stepwise basal-bolus n=191 p<0.025* p<0.05* p<0.05* p<0.01* Riddle, MC et al. Diabetes, Obesity and Metabolism 2014. 16: 396–402,
- 68. 69
- 69. Proposed progressive insulin strategies in type 2 diabetes. *Log = rapid-acting insulin analogues (lispro, aspart, glulisine
- 70. Initiating & Adjusting Insulin Continue regimen; check HbA1c every 3 months If FBG in target range, check BG before lunch, dinner, & bed; depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin If HbA1c ≤7%... Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range If HbA1c 7%... Hypoglycemia or FG >3.9 mmol/L (70 mg/dL): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range: add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range: add rapid-acting insulin at dinner Continue regimen; check HbA1c every 3 months Target range: 3.9-7.2 mmol/L (70-130 mg/dL) If HbA1c ≤7%... If HbA1c 7%... Nathan DM et al. Diabetes Care 2009;32(1):193-203.
- 71. Conclusions In the early stages of insulin therapy, most individuals seem to achieve favorable glycaemic control with basal insulin alone, or in combination with a single prandial insulin injection. The addition of a single prandial insulin injection at the largest meal is well tolerated and associated with significant improvements in (HbA1c), low rates of hypoglycaemia & limited weight gain. More people achieve recommended HbA1c targets with a basal-plus strategy, compared with twice-daily premixed insulin therapy, with lower rates of hypoglycaemia. Step-by-step approach with the basal-plus strategy is a promising alternative method of insulin intensification that allows for individualization of treatment and may delay progression to a full basal–bolus insulin replacement therapy for many individuals. Owens D. Diabet Med. 2013 Mar; 30(3): 276–288.
- 72. Stepwise Intensification of Treatment for Continuity of Control Progressive deterioration of -cell function Lifestyle changes Oral agents Basal Add basal insulin and titrate Basal plus Add prandial insulin at main meal Basal bolus Additional prandial doses as needed FBG above target HbA1c above target HbA1c above target FBG at target HbA1c above target Adapted from Raccah D et al. Diabetes Obes Metab 2008;10(2):76-82. When glycaemic targets are not met: – Treatment should be changed to the next ‘step’ – Currently, therapy change is often too late – Earlier treatment modification is necessary