Updates in Insulin Injection Technique: Data and Recommendations

Transcription

1 Updates in Insulin Injection Technique: Data and Recommendations Maureen Mo Bressett, RPh, MSHA Senior Medical Science Liaison BD Medical Affairs: Diabetes Care

2 Disclosures Maureen Bressett is an employee of Becton Dickinson 2

3 Objectives 1. Identify patient barriers to insulin therapy 2. Articulate the role of insulin injection technique in decreasing glucose variability 3. Discuss skin and SQ fat thickness studies in adults, pediatric and obese subjects with diabetes, and how skin and SQ fat thickness relate to injection technique 4. Convey top 10 recommendations from latest insulin injection technique guidelines 3

4 Agenda Why is this important to you? Diabetes Prevalence (2012 CDC:29 Million, 9.3% US pop) ADA/EASD Position Statement Surveys (Barriers and Injection Habits) Insulin Injection Guidelines Glucose Variability and Insulin Absorption Clinical Trials Skin & SQ Fat Thickness (adults) Safety /Efficacy comparison of different pen needle lengths Top Ten Take Home Points: Guidelines 4

5 AD/EASD Position Statement:

6 Psychological Insulin Resistance: Patient Barriers/Beliefs 60% patients surveyed would not easily inject insulin (1) Failure: promised outcome for poor adherence Serious side effects 65% patients not confident in ability to self-manage 1.Davidson J. Diabet Med. 2006;23(suppl. 4):163 (P457) 6

7 History of Insulin Needles: Product Innovations 7

8 Traditional Insulin Injection Technique Inject at a 45 degree angle using skin pinch up or skin fold Why: to avoid IM injections with needles then available: Muscle not lifted Correct Incorrect Lo Presti et al; Pediatric Diabetes 2012:13:

9 Insulin injection habits of 4300 patients 21% of patients use same injection site all day 32% have no particular injection routine 49% use an 8mm needle U.S.: >12% use 12.7mm needle 63% had not changed needle length since starting insulin Thigh injection: 27% do not use skin fold 76% inject at 90º 28% did not recall ever having an injection site inspection by their HCP Findings confirmed beliefs: these habits impact insulin absorption. Findings used in development of insulin injection guidelines De Connick C. et al. J. Diabetes 2010;2:

10 Recent injection guidelines 1. Frid A, et al. New injection recommendations for patients with diabetes. Diabetes & Metabolism. 2010;36 (suppl): S12. 10

11 Glucose Variability Factors in Patients with Diabetes Food composition, amount, duration of meal Exercise Stress, illness, injury, hospitalization Medications Endogenous Factors Insulin absorption (exogenous) Glucose variability may lead to increased oxidative stress and increased risk of microvascular complications 11

12 Factors Affecting Insulin Absorption Type of insulin Insulin concentration and dose volume What Body site Injection site: warm, rubbed, or exercised Subcutaneous vs. intramuscular How Lipohypertrophy What is injected is important, but so is How it s injected. 12

13 Insulin Uptake: Body Site and Depth of Injection Body site: Insulin analogs: similar time profiles across sites Human insulins (Regular, NPH) Abdomen > Arm Thigh > Buttock Depth of injection: Regular insulin absorbed at similar rates when injected into deep or superficial SC tissue All Insulins absorbed faster when given IM vs. SC 13

14 % Remaining radioactivity Injection Depth: Subcutaneous Tissue Absorption of regular insulin is faster in the abdomen than in the thigh Regular insulin is absorbed at similar rates at both sites, when injected into deep vs. superficial subcutaneous tissue I-Regular insulin(sc) Thigh Abdomen 60 min 120 min 175 min Thigh - Deep Injection Abdomen - Deep Injection Thigh - Superficial Injection Abdomen - Superficial Injection Frid A et al., Diabetic Medicine 1992;9;

15 Plasma Immunoreactive Insulin (mu/i) IM vs SC Injection Exercise affects insulin absorption: Plasma Glucose (mmol/l) Exercise significantly increased the absorption of human insulin when injected IM vs SC into the thigh 1 The increased insulin absorption with IM injection after exercise resulted in a significantly greater plasma-glucose lowering effect SC Exercise IM 8 Exercise IM 20 SC Time (min) Time (min) 1 Frid A et al. Diabetes Care 1990;13:

16 Lipohypertrophy affects insulin absorption Defined: Fatty lumps at or around insulin injection sites Risk factors: Duration of insulin therapy, number of daily injections, daily insulin dose Infrequent changing of needles Lack of injection site rotation Why is it a problem: Decreases insulin absorption May increase glucose variability Insensitive to pain How to avoid: Appropriate site rotation Perform regular inspection Change needle each injection Vardar B, Kizilci S, et al. DRCP. 77(2007) Volkova N, Davidenko I. Diabetes Mellitus 2011; 2:

17 Rotation of sites: One suggestion Divide abdomen or thigh in halves or quadrants, Use one quadrant or half per week, 1 cm between sites, always moving counterclockwise Frid A, et al. New injection recommendations for patients with diabetes. Diabetes & Metabolism. 2010;36 (suppl): S12. 17

18 Insulin Injection: Target Site Epidermis Dermis Subcutaneous tissue Muscle Tissue Blood Flow: Dermis Small, swift flow Highly variable Subcutaneous Tissue Slow flow Very stable Muscle Large, swift flow Highly variable Insulin absorption in not fastest in the subcutaneous fat tissue, but it is the most consistent, making it the preferred location for insulin injection. 18

19 Three Factors that determine insulin depot Thick SC tissue Thin SC tissue Epidermis Dermis SC tissue Epidermis Dermis SC tissue Muscle Muscle Skin and SC tissue thickness plus needle length predict insulin depot: ID, SC, IM Needle: long enough to cross skin into SC, but short enough to not enter the muscle. 19

20 Clinical Study: Skin Thickness Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations Gibney M, et al. Curr Med Res Opin 2010;26:

21 Demographics N = 388; 55% male Diagnosis of DM minimum: 1 year Ages years, mean 51.8 (40% > 60 years) 40% Caucasian; 25% Asian; 16% Black; 14% Latino BMI mean 29.9 kg/m 2 ; range ~19-64 kg/m 2 ;42% 30 kg/m 2 28% T1DM; 72% T2DM 39% of T2DMs on insulin Gibney M, et al. Curr Med Res Opin 2010;26:

22 mm mm mm mm Skin Thickness across different demographics Approximately mm* ( mm) regardless of gender, age, ethnicity, BMI 1 Gender Ethnicity Age BMI 1 Gibney M, et al. Curr Med Res Opin 2010;26(6): *Mean skin thickness results with 95% CI combined at all 4 injection sites 22

23 Estimate: IM injection risk from ST/SCT Data Pen Needle Length IM 4 mm 0.4% 5 mm 1.8% 6 mm 5.7% 8 mm 15.3% 12.7 mm 45.0% * Assume 90 insertion, no pinch-up. * All injection sites combined (N = 1208) * Geometric estimates only. No injections given. Gibney M, et al. Curr Med Res Opin Gibney M, et al. Curr Med Res Opin 2010;26: ;26:

24 MRI Imaging of Injection Placement Right thigh of 56 year old male; BMI = 25.2 kg/m2 4, 5, 6, & 8mm injections conducted using MRI imaging Saline injected (equivalent 4 units U-100 insulin) 90 degree insertion, no skin pinch up Gibney M, et al. Curr Med Res Opin 2010;26:

25 MRI: male-right thigh 4mm: SC tissue 5mm: SC tissue 6mm: Muscle fascia 8 mm: Muscle Gibney MA, et al. Skin and subcutaneous adipose layer thickness in adults with diabetes at sites used for insulin injections: implications for needle length recommendations. Curr Med Res Opin. 2010; 26 (6): MRI images provided by Drs. Anders Frid and Björn Lindén,

26 Study Conclusions: Skin & SC Tissue Thickness Skin thickness varies minimally, regardless of BMI, gender, race, age <3 mm in most patients, all injection sites, Skin thickness varies slightly by body site (thigh thinnest by ~0.6 mm) statistical differences not clinically relevant Gibney M, et al. Curr Med Res Opin 2010;26:

27 Skin & Subcutaneous Thickness at Injecting Sites in Children with Diabetes: Ultrasound Findings & Recommendations for Injection Lo Presti et al; Pediatric Diabetes 2012:13:

28 Baseline Characteristics Type 1 DM Subjects 2-6 years 7-13 years years N = Males/Females 18/13 29/20 10/11 Mean Age Mean BMI Mean HbA1c (%) Lo Presti et al; Pediatric Diabetes 2012:13:

29 Skin + SQ Tissue Thickness in Children Body Site (mm ±SD) 2-6 years 7-13 years years Arm 4.89 ± ± ±1.94 Thigh 6.05 ± ± ±2.10 Abdomen 6.12 ± ± ±2.91 Buttocks 6.53 ± ± ±2.81 Using needles longer than the ST + SQT likely to result in IM injection Lo Presti et al; Pediatric Diabetes 2012:13:

30 Calculated Incidence of IM Injections All Injection Sites Combined Needle Length 2-6 Years (n=248) 7-13 Years (n=392) Years (n=168) 4 mm 20.2% 4.6% 2.4% 6 mm 66.5% 38% 34.5% 8 mm 83.9% 65.3% 66.1% 12.7 mm 97.2% 93.9% 96.4% *All injection sites combined (arm, thigh, abdomen, buttocks) Number of measurements Lo Presti et al; Pediatric Diabetes 2012:13:

31 Age 2-6 Years: Skin Pinch-Up! Based on mean values of skin + SC thickness in children- it seems preferable for all children to use shortest needle possible. Currently: 4 mm pen needle. recommend pinch-up technique in children 2-6 years old at all sites, even when using 4 mm pen needle. Lo Presti et al; Pediatric Diabetes 2012:13: Muscle not lifted Correct Incorrect Lo Presti et al; Pediatric Diabetes 2012:13:

32 Clinical Study: Needle Length Comparisons Comparative glycemic control, safety and patient ratings for a new 4 mm\32g insulin pen needle in adults with diabetes Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

33 Subject Flow and Endpoints Baseline Fructosamine Period 1 Period 2 Fructosamine Pain vs. Usual Needle Leakage Diary Survey Fructosamine Pain vs. Prior Needle Leakage Diary Survey Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

34 Fructosamine changes: 4mm pen needle provided equivalent glycemic control Pen Needle Mean % Absolute Change (95% CI) p-values 4 mm vs. 5 mm 4.9% (3.8, 6.0) mm vs. 8 mm 5.5% (4.5, 6.4) mm pen needle provided equivalent glycemic control compared to 5 & 8 mm pen needles in both absolute and relative mean % changes 1 1 Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:(6)

35 Relative Pain (VAS) Group (N) Mean Difference* (mm) P-value 4mm/5mm (68) mm/8mm (69) <0.001 * Visual Analogue Scale (VAS) 4mm Less Painful No Difference in Pain at Zero (mm) 5 or 8 mm Less Painful -75mm -50mm -25mm 0 25mm 50mm 75mm Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

36 Leakage at Injection Site Needle Length Subjects (N) Percent (%) 4 mm % 5 mm 83 47% 8 mm 81 56% No evidence of increased leakage with 4mm needle Most droplets for all lengths reported as < 1 unit) Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

37 Safety Event Frequency of Event by Needle Used at Time of Event 4 mm (N=173) n (%) 5 mm (N=89) n (%) 8mm (N=84) n (%) Hypoglycemia* 9 (5.2%) 5 (5.6%) 4 (4.8%) Hyperglycemia 0 (0%) 2 (2.2%) 1 (1.2%) *Severe, unexplained hypoglycemic events Rates of severe, unexplained hypoglycemia/ hyperglycemia comparable across all needle lengths. Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

38 Study Conclusions: 4mm x 32G vs. 5mm & 8mm x 31G 4mm PN equivalent glucose control compared to 5mm & 8mm PN in adult patients Similar safety profile, no increase in reported leakage 4 mm PN less painful Hirsch LJ, Gibney MA, Albanese J, et al. Curr Med Res Opin 2010;26:

39 Glycemic Control, Reported Pain, & Leakage with a 4 mm x 32G Pen Needle in Obese & Non-Obese Adults Post-hoc analysis by BMI (non-obese vs. obese) as sub-groups within treatment groups from the original BD Nano study Objective: To determine if obesity (BMI 30 kg/m2) influenced glycemia, pain, or leakage Hirsch LJ, Gibney MA, Lingzhi LI, et al. Curr Med Res Opin 2012;28 39

40 Obesity subset analysis conclusions 4mm is provided equivalent glycemic control compared to 5mm & 8mm pen needles in both obese (BMI 30) & non-obese (BMI <30) patients In obese patients, 4mm was less painful than 5mm or 8mm needle No increased leakage compared with other needle lengths 4mm is a viable option in both obese & non-obese patients Hirsch LJ, Gibney MA, Lingzhi LI, et al. Curr Med Res Opin 2012;28 40

41 Top 10 Injection Recommendations 1. Needle Length Children and adolescents should use a 4, 5 or 6 mm needle. -No medical reason for needles > 6 mm. 2. The 4, 5, and 6 mm needles may be used by any adult patient, including obese -No medical reason for pen needles > 8 mm in adults. -Begin Initial therapy with shorter lengths. 3. Lipohypertrophy -Inspect injection sites and train patients to do so -Do not inject into lipohypertrophy sites. Frid A, et al. New injection recommendations for patients with diabetes. Diabetes & Metabolism. 2010;36 (suppl): S12. 41

42 Top 10 Injection Recommendations 4. Current strategies to prevent and treat lipohypertrophy -Use purified human Insulins or analogues, - Rotate injection sites with each injection, - Use larger injecting zones - Do not re-use needles. 5. Site Rotation: Teach easy-to-follow rotation scheme at onset injection therapy 6. Injection Sites: -Insulin analogues and GLP-1 agents uptake not site specific: use any site -To increase uptake rate, inject regular human into abdomen -To decrease uptake rate & reduce risk of hypoglycemia, inject NPH into thigh/buttock Frid A, et al. New injection recommendations for patients with diabetes. Diabetes & Metabolism. 2010;36 (suppl): S12. 42

43 Top 10 Injection Recommendations 7. Avoid IM injections of long-acting analogues to decrease risk of hypoglycemia. 8. Beginning Injections in Children. - Younger children may be helped by distraction techniques (no trickery) or play therapy, i.e. injecting into a stuffed animal) - Older children respond better to cognitive behavioral therapies. 9. Injections in Adolescents: -Reassure Adolescents that no one manages diabetes perfectly all the time 10. Injections in Adult Type 2 patients. - Prepare newly-diagnosed T2D patients for likely future insulin therapy. - Explain natural, progressive nature of T2D and that insulin treatment is not a sign of failure. Frid A, et al. New injection recommendations for patients with diabetes. Diabetes & Metabolism. 2010;36 (suppl): S12. 43

44 Summary: Things to consider Diabetes is complex Insulin Therapy is complex Injection Technique matters Needles play role in insulin absorption, safety and adherence 44

45 Questions??? 45