Injecting Insulin into Out Patient Practice

Transcription

1 Injecting Insulin into Out Patient Practice Kathleen Colleran, MD Associate Professor UNMHSC 4/22/10 Overview Natural history of Type 2 diabetes Reasons clinicians are reluctant to start insulin therapy Reasons patients are reluctant to start insulin therapy Types of insulin therapies Types of insulin delivery methods Initiating insulin therapy in patients

2 Natural History of Type 2 Diabetes Years from diagnosis Onset Diagnosis Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Pre-diabetes Microvascular complications Macrovascular complications Type 2 diabetes Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26: ; Nathan DM. N Engl J Med. 2002;347: Progressive Decline of β-cell Function in the UKPDS β-cell Function (% β) Years Adapted from UK Prospective Diabetes Study (UKPDS 16) Group. Diabetes. 1995;44:

3 Management of hyperglycemia in type 2 diabetes BMJ. 2006;333: What is the Natural History? BMJ. 2006;333:

4 ADOPT outcomes Cumulative Incidence of Monotherapy Failure at 5 Years NEJM 2006;355: Stepwise Management of Type 2 Diabetes Biggest Clinical Hurdle??? Insulin Oral monotherapy Oral combination Oral plus insulin Diet & exercise Adapted from Williams G. Lancet 1994; 343:

5 Barriers to insulin use Systemic Barriers Cost Training Stigma Clinician Barriers Fear of SE Clinical inertia Time Patient Barriers Physician-Rated Barriers to Optimal Diabetes Care Patient-related Health-system related Patient nonadherence to nonpharmacologic therapy Patient lack of motivation Patient nonadherence to pharmacologic therapy Patient lack of education Not enough time Formulary restrictions Insufficient reimbursement for effort required Limited number of office visits Complexity of cases CADRE survey, Mean rating

6 Barriers to Starting Insulin Clinician Clinical inertia Clinic time constraints/ lack of resources Fear of hypoglycemia Weight gain Patient reluctance Clinical Inertia Failure to advance therapy when required 10 9 Last HbA 1C Value Before Abandoning Treatment 9.6% 9.1% 8.8% 8.6% % Mean HbA 1C at last visit ADA Goal Sulfonylurea Diet/Exercise Combination Metformin 2.5 years 2.9 Years 2.2 Years 2.8 Years 1 Brown et al. The Burden of Treatment Failure in Type 2 Diabetes. Diabetes Care 27: ,

7 Clinical Inertia: Percentage of Subjects advancing when HbA 1C > 8% %Age of Subjects % At Insulin Initiation, the average patient had: 5 years with HbA 1C > 8% 10 years with HbA 1C > 7% 35.3% 44.6% 18.6% 0 Diet Sulfonylurea Metformin Combination Brown et al. The Burden of Treatment Failure in Type 2 Diabetes. Diabetes Care 27: , 2004 Clinical Inertia 4207 Person-Years of Followup At Insulin Initiation, patients who had failed combination therapy Had a median HbA 1C of 9.9% The high median HbA1C that preceded the initiation of insulin in our population is particularly troubling and suggests that there are substantial barriers to its Initiation Cook et al: Glycemic Control continues to deteriorate after Sulfonylureas Are Added to Metformin Among Patients with Type 2 Diabetes. Diabetes Care 28: ,

8 EVERY 24 HOURS New Cases 4,100 Deaths 810 Amputa6ons 230 Kidney Failure 120 Derived from NIDDK, Na6onal Diabetes Sta6s6cs fact sheet. HHS, NIH, Blindness 55 What about Insulin? Relentless progressive nature of disease Insulin is the most effective agent glucose lowering only limited by hypoglycemia Delaying insulin may have detrimental effects Glucotoxicity to β cells Post prandial glucose reduction may be associated with reduced CV risk 1,2 Most patients will eventually need it Basal insulin is the first to go and easiest to replace 1 Circulation 110: ; Diabet Med 21: , Clinical Diabetes 23(2):78-86, 2005

9 HbA1c Reduction with Treatment Therapy Lifestyle changes, diet & exercise Medication Reduction in HbA1c None % Single oral agent Sulfonylurea or Metformin % Combinations with oral agents Insulin with other agent Sulfonylurea, Metformin Alpha-glucosidase inhibitor Thiazolidinedione Exenatide Sulfonylurea, Metformin Thiazolidinedione Pramlintide % % Insulin Insulin alone >2% Insulin Preparations Class Human insulins Agents Regular, NPH Insulin analogues Aspart, glulisine, lispro glargine, dettimer Premixed insulins NPH/Reg 70/30, 50/50 Humalog mix 75/25 Novolog mix 70/30

10 Human Insulins and Analogues Typical Times of Action Insulin Preparations Onset of Action Peak Duration of Action Aspart, glulisine, lispro ~15 minutes 1 2 hours 4 6 hours Human regular minutes 2 4 hours 6 8 hours Human NPH, 2 4 hours 4 10 hours hours Human ultralente 4 6 hours 8 16 hours hours Glargine/Detimer 2 4 hours Flat ~24 hours Insulin Analogues A-chain B-chain Asp Human Insulin Dimers and hexamers in solution Aspart Limited self-aggregation Monomers in solution Lys Gly Glu Lys Pro Arg Arg Glulisine Limited self-aggregation Monomers in solution Lispro Limited self-aggregation Monomers in solution Glargine Soluble at low ph Precipitates at neutral (subcutaneous) ph

11 New Insulin Analogs More closely match normal physiology Rapid acting agents: Lower post prandial glucose excursions Shorter durations of postprandial hyperglycemia Significantly reduced incidence of severe hypoglycemia in patients with T2DM Combination agents (rapid plus intermediate acting insulins): improved postprandial control with reduced hypoglycemia Clinical Diabetes. 23(2):78-86, Insulin Response in Non-Diabetics Insulin Effect B L S HS B

12 Action Profiles of Bolus & Basal Insulins lispro/aspart 4 6 hours regular 6-10 hours BOLUS INSULINS BASAL INSULINS Plasma Insulin levels NPH hours detemir ~ 6-23 hours (dose dependant) glargine ~ hours Hours Note: action curves are approximations for illustrative purposes. Actual patient response will vary. Mayfield, JA.. et al, Amer. Fam. Phys.; Aug. 2004, 70(3): 491 Plank, J. et.al. Diabetes Care, May 2005; 28(5): Initiating Basal Insulin Weight based U/kg or Set dose Units qhs Fasting target mg/dl Increase by 1 U/day until target met Regular contact phone/ /fax

13 Options for Basal Insulin NPH Insulin Glargine/Detemir Insulin Effect B L S HS B L S Starting Basal Insulin for Type 2 Diabetes Bedtime NPH Added to Diet 12 Patients Treated for 16 Weeks Plasma glucose (mg/dl) Diet only Bedtime NPH 200 NPH Time of day Cusi K et al. Diabetes Care. 1995;18:

14 Caveats for basal insulin There is not a maximum dose For Full Basal Coverage NPH BID Detimer/gargine have variable absorption by person may need bid dosing Bed time hyperglycemia Nocuturnal hypoglycemia Dose >75 units Key considerations for Insulin therapy Basal-bolus regimens most closely simulate normal physiology but have drawbacks: Requires motivated patient and physician Requires comprehensive training in carb counting and insulin adjustment Must tailor treatment plan to each patient Start low (0.15 U/kg body wt/day), titrate steadily Monitor and adjust therapy until goals achieved Clinical Diabetes. 23(2):78-86, 2005.

15 The Basal-Bolus Insulin Concept Basal insulin Controls glucose production between meals and overnight Nearly constant levels 50% of daily needs Bolus insulin (mealtime or prandial) Limits hyperglycemia after meals Immediate rise and sharp peak at 1 hour postmeal 10% to 20% of total daily insulin requirement at each meal For ideal insulin replacement therapy, each component should come from a different insulin with a specific profile The Basal-Bolus Concept Insulin Effect B L S HS B

16 Options for Pre-meal Insulin Insulin Effect Regular Insulin aspart B L S HS B Basal-Bolus Insulin Treatment With Insulin Analogues Lispro, glulisine, or aspart Insulin Levels µu/ml B L D Glargine/Detimer/NPH Normal pattern Time of day B=breakfast; L=lunch; D=dinner

17 Mixtures of Pre-meal Insulins Insulin Effect Regular/NPH Combined effect B L S HS B Take home points on Insulin Rx Start Insulin earlier Best option if A1C >8.5 despite oral therapy Basal insulin added to oral medications a safe and effective way to initiate Titrate to effect, if still not controlled, go to multiple daily injections Newer Insulin analogs are safer less hypoglycemia

18 Barriers to Starting Insulin Patient related Inconvenience Pain False perceptions Fear of needles Fear of hypoglycemia Injection Aids Insulin pens Insertion aids (Autoject, Inject-Ease, NeedleAid) Dosing devices (InnoLet) Needle guides & stabilizers (Holdease, Inject Assist, Vial Syringe Guide) Insulin pumps

19 Insulin Injection Devices Insulin pens Faster and easier than syringes Improve patient attitude and adherence Have accurate dosing mechanisms convenience Injection aids

20 Trade-off Between Hypoglycemia & Complications Rate pf progression of retinopathy (per 100 patient years) Relative risk Severe hypoglycemia 120 of retinopathy HbA1c (%) 60 0 Rate of severe hypoglycaemia (per 100 patient years) DCCT Research Group, 1993 Continuous Glucose Monitoring (CGM) CGMS ipro Recorder MiniMed Paradigm REAL-Time System Guardian REAL-Time System HCP Patient Patient 3 day test to provide retrospective CGM data Provides real-time CGM information directly to an insulin pump Provides real-time CGM information to an external monitor 40

21 Sensor Detects Interstitial Fluid (ISF) Glucose Sensor glucose (G2) correlates well with capillary glucose when glucose levels are stable ISF measurements may lead or lag capillary measurements by 5-15 minutes Overall, the sensor glucose trends are more important than the absolute measurements Plasma (V1) (V2) Illustration adapted from Rebrin K, et al. Am J Physiol 1992;277:E561 E571. False Perceptions to Insulin Therapy Punishment Failure Experience of other Family members Last resort

22 Summary Insulin Therapy Replaces complete lack of insulin in type 1 diabetes Supplements progressive deficiency in type 2 diabetes Basal insulin added to oral agents can be used to start Full replacement requires a basal-bolus regimen Hypoglycemia and weight gain are the main medical risks New insulin analogues and injection devices facilitate use Case studies This is on you