Debra A. Ignaut, R.N., B.S., C.D.E., and Haoda Fu, Ph.D.

Transcription

1 Journl of Dietes Science nd Technology Volume 6, Issue 2, Mrch 2012 Dietes Technology Society TECHNOLOGY REPORT Comprison of Insulin Diluent Lekge Postinjection Using Two Different Needle Lengths nd Injection Volumes in Oese Ptients with Type 1 or Type 2 Dietes Mellitus Der A., R.N., B.S., C.D.E., nd Hod Fu, Ph.D. Astrct Bckground: Smller guge, shorter needles hve een shown to e s sfe nd effective for insulin delivery s longer needles in mny ptients. However, in oese ptients with dietes, results hve een inconsistent with regrd to the impct of needle length on lekge of injectte. Methods: A single-lind, rndomized, two-period, crossover study compred injections with 5 mm needles to 8 mm needles regrding lekge, pin, leeding, nd ruising t dominl injection sites in oese ptients with dietes using 20- nd 60-unit (U) volume equivlent injections of sterile insulin diluent. Results: Fifty-six ptients (54% mle; men ge 56 yers; men ody mss index of 36 kg/m 2 ) with type 1 (n = 13) or type 2 (n = 43) dietes prticipted. Medin lekge (U) ws similr for oth needles [0.04 (5 mm/20 U) vs 0.02 (8 mm/20 U), P =.32; nd 0.04 (5 mm/60 U) vs 0.02 (8 mm/60 U), P =.48]. Pin scores (men) were similr [1.27 (5 mm/20 U) vs 1.14 (8 mm/20 U), P =.75, nd 1.68 (5 mm/60 U) vs 0.95 (8 mm/60 U, P =.21)]. The proportion of injections with leeding [10.8% (5 mm/20 U) vs 5.83% (8 mm/20 U), P =.23, nd 4.92% (5 mm/60 U) vs 6.56% (8 mm/60 U), P =.73] nd the proportion of ptients with ruising [8.11% (5 mm/20 U) vs 10.81% (8 mm/20 U), p =.56, nd 21.05% (5 mm/60 U) vs 26.32% (8 mm/60 U), p =.65] t injection sites were similr. Men ruise size (mm) [0.73 (5 mm/20 U] vs 2.68 (8 mm/20 U), P =.23; nd 1.11 (5 mm/60 U) vs 4.21 (8 mm/60 U), P =.08] t injection sites ws similr. Conclusions: This study supports the suitility of the 5 mm needle for the injection of insulin in oese ptients with dietes. J Dietes Sci Technol 2012;6(2): Author Affilition: Eli Lilly nd Compny, Indinpolis, Indin Arevitions: (BMI) ody mss index, (GEE) generlized estimting eqution, (SAE) serious dverse event, (SD) stndrd devition, (U) unit, (VAS) Visul Anlog Box-21 Scle for Pin Keywords: dietes, lekge, needle length, oesity Corresponding Author: Der A., R.N., B.S., C.D.E., Eli Lilly nd Compny, Drop Code 6024, Indinpolis, IN 46285; emil ddress dignut@lilly.com 389

2 Introduction Side effects of sucutneous insulin injections cn include lekge, pin, leeding, nd ruising t the injection site. These side effects my compromise insulin dose, increse ptient discomfort, nd compound the nxiety experienced y mny ptients towrd insulin injections. Injection-relted nxiety is thought to e mjor contriutor to psychologicl insulin resistnce. 1 When given the choice etween longer needle (12.7 mm) nd shorter needle (6 mm), most people would likely choose the shorter needle. 2 Smller, shorter needles hve een shown to e sfe nd effective for insulin delivery while reducing ptient discomfort. 3 When 5 mm nd 8 mm needles were compred in peditric nd dult popultions, the 5 mm needle ws found to e s efficcious nd sfe s n 8 mm needle. 4 Oese ptients with dietes re often dvised to use longer needles ( 8 mm) ecuse of clinicl perception tht longer needles re needed for correct injection into thicker lyer of sucutneous ft. However, there is no compelling clinicl evidence tht injecting deep into the sucutneous ft produces superior efficcy to n injection into the superficil sucutneous ft. Three studies hve exmined lekge of injectte in oese ptients with dietes. 2,5,6 In study compring 8 mm pen needles with 12.7 mm pen needles, oese sujects were significntly more likely to experience insulin lekge from their injection sites compred to nonoese sujects, regrdless of needle length. 6 Among oese ptients, lthough the use of 31 G 6 mm vs 29 G 12.7 mm needles produced comprle hemogloin A1c vlues, doule-lind pin nd lekge scores, convenience, nd ese of use; ptients preferred the shorter needle. 2 A multicenter, open-lel, crossover study in oese ptients with type 1 nd type 2 dietes mellitus demonstrted equl efficcy nd sfety with 5 mm needles s compred with 8 mm needles. 5 Although two of the forementioned studies supported use of shorter needles in oese ptients with dietes, the perception continues tht longer needles should e used in oese ptients. No studies to dte hve compred 5 mm needles with 8 mm needles using different injection volumes nd pin ssessments in oese ptients with dietes linded to needle length. This study compred investigtor-dministered injections of 20- nd 60-unit (U) equivlent volumes of preserved sterile insulin diluent using 5 mm needles with similr injections using 8 mm needles regrding lekge, pin, leeding, nd ruising t dominl injection sites in oese ptients with dietes. Methods Ptients Eligile ptients were men nd women 18 yers of ge with type 1 dietes or type 2 dietes nd ody mss index (BMI) 30.0 kg/m 2, who were injecting insulin t lest once dily for t lest 6 months prior to screening procedures. Ptients were excluded if they hd more thn two dominl surgicl scrs longer thn 2 inches within the provided injection grid re, hd self-perceived dullness or loss of senstion on either side of the domen, hd known hypersensitivity or llergy to preserved sterile insulin diluent or insulin, were tking nticogulnts or ntipltelet medictions other thn spirin, hd dignosis or pst history of significnt leeding disorder, or hd significnt weight chnge (± 10% ody weight) within 6 weeks prior to screening procedures. Study Design This study ws conducted in ccordnce with the provisions of the Declrtion of Helsinki nd Good Clinicl Prctice guidelines. Ethicl review ords pproved the study protocol for ech study site, nd investigtors otined sujects written informed consent efore ny study procedures. This ws rndomized study conducted t two outptient centers in the United Sttes. Ptients were linded to needle length. Ptients were rndomly ssigned to one of eight sequence groups in order to reduce is during study execution. A two-period crossover design ws used to compre oth 20 U (200 ml) nd 60 U (600 ml)-equivlent volume injections of preserved sterile insulin diluent dministered with oth 5 mm nd 8 mm needles using the HumPen Memoir (Eli Lilly nd Compny, Indinpolis, IN) insulin pen injector. The primry ojective of this study ws to compre injections with 5 mm nd 8 mm needle lengths with respect to lekge t the injection site. The secondry ojectives were to compre injections with 5 mm nd 8 mm needle lengths with respect to pin intensity, leeding, nd ruising t the injection site. 390

3 Ptients were rndomized y dose nd dominl qudrnt (left nd right lower) to receive either 20 U (200 ml) or 60 U (600 ml)-equivlent volume injections of preserved sterile insulin diluent. Once rndomized, ll ptients were injected t lest three times (nd up to five times) per series with HumPen Memoir insulin pen injector fitted with either 5 mm or 8 mm needle. The gol ws to chieve three successful injections for ech series. A successful injection ws defined s n injection with no visile leeding the presence of lood t the injection site would hve interfered with ccurte mesurement of lekge. Lekge ws ssessed using filter pper nd tred, clirted nlyticl lnce. After completion of the injection, filter pper ws lid on the injection site to sor ny postinjection lekge. The filter pper ws then plced on the nlyticl lnce to otin the weight (in mg) of insulin diluent leked from the injection site. Lekge dt were converted to volume using the following conversion formul: 10,000 mg = 1000 mg/mg 10 mg = 10 ml = 1 U. Pin mesurements were ssessed using the vlidted Visul Anlog Box-21 Scle for Pin (VAS) Only the first injection with ech needle length ws ssessed for pin to reduce the possiility of pin ftigue. Immeditely following the injection, the prticipnt ws sked to rte the pin ssocited with ech injection on scle of 0 to 20. All injection sites were oserved immeditely postinjection y the investigtor or designee, nd the presence of visile leeding ws recorded (yes/no). All injection sites were ssessed for ruising 1 to 3 dys following ech series of injections. Sttisticl Methods P-vlues for comprison of lekge medins were clculted using the sign test. Type one errors were controlled y gtekeeping strtegy. The incidence of ruising nd ruise size were nlyzed using the McNemr test nd Student s t-tests, respectively. The incidence of leeding ws nlyzed using generlized estimting eqution (GEE) model. P-vlues for comprison of pin scores were clculted using Student s t-tests. Results Ptient Chrcteristics Fifty-six ptients entered the study nd were rndomly ssigned to tretment, nd ll ptients completed the study. Ptients were generlly middle-ged [men ± stndrd devition (SD) ± 9.77 yers], mle (53.57%), hd men (± SD) BMI of ± 5.54 kg/m 2, nd the mjority hd type 2 dietes (76.79%) (Tle 1) nd hd dietes of long durtion (men ± SD ± 8.65 yers). Most ptients (98.21%) originted from the United Sttes. Lekge Anlysis A summry nd nlysis of lekge is presented in Tle 2. There ws no significnt difference etween the 5 mm needle nd the 8 mm needle with respect to medin lekge with either the 20 U or 60 U equivlent volume. Tle 1. Ptient Chrcteristics Chrcteristic Totl (N = 56) Age (yers), men ± SD ± 9.77 Sex, n (%) Mle 30 (53.57) Femle 26 (46.43) BMI (kg/m 2 ), men ± SD ± 5.54 Dietes type, n (%) Type 1 13 (23.21) Type 2 43 (76.79) Origin, n (%) Mexico 1 (1.79) United Sttes 55 (98.21) (n) numer of ptients, (N) totl numer of ptients. Tle 2. Anlysis of Lekge Needle length (mm) Injection volume (U) N Men (U) Medin (U) SD % CI (U) (0.02, 0.06) (0.02, 0.04) (0.01, 0.13) (0.01, 0.04) P vlue (N) totl numer of ptients The CI ws clculted for medin using exct order sttistics. P vlues for comprison of medins were clculted using the sign test. 391

4 Pin Scores There ws no significnt difference etween the 5 mm needle versus the 8 mm needle with respect to pin score with either the 20 U or 60 U equivlent volume (Figure 1). Men ± SD differences (5 mm minus 8 mm) in pin score for 20 U nd 60 U equivlent volumes were 0.14 ± 2.56 nd 0.74 ± 2.49, respectively. Bruising A summry of the incidence of ruising nd ruise size y injection volume is provided in Tle 3. There were no significnt differences etween the 5 mm nd 8 mm needles with respect to incidence of postinjection ruising t the injection site with either injection volume. In ddition, there were no significnt differences etween the 5 mm nd 8 mm needles with respect to ruise size. The men (± SD) differences (5 mm minus 8 mm) in ruise size (mm) for 20 U nd 60 U equivlent volumes were ± 9.79 mm nd ± 7.38 mm, respectively. Bleeding There were no significnt differences etween the 5 mm nd 8 mm needles with respect to the incidence of postinjection leeding t the injection site. A summry of leeding y injection volume is provided in Tle 4. Sfety There were no serious dverse events (SAEs) reported during this study. Discussion Smller needles my reduce ptient discomfort nd hve positive impct on psychologicl insulin resistnce. In this single-lind, rndomized tril of oese ptients with type 1 or type 2 dietes, there were no oserved differences etween the 5 mm needle nd the 8 mm needle with respect to insulin diluent lekge, pin intensity, leeding, or ruising t injection sites with 20 U- or 60 U-equivlent volumes. There were no SAEs reported during study execution. The study results suggest tht the 5 mm needle does not pose ny dditionl risk for use in the oese popultion with dietes compred with the 8 mm needle. This study provides evidence supporting the suitility of the 5 mm needle for the injection of insulin in oese ptients with dietes. Similr to the results of the study y Kreugel nd coworkers, 5 we found no difference etween the 5 mm nd 8 mm needles with respect to ruising nd pin. However, in contrst to the Kreugel study, where Figure 1. Pin scores using VAS 0 20 point scle. P vlues were clculted using Student s t-test. (N) totl numer of ptients, (SEM) stndrd error of the men. Tle 3. Incidence of Bruising nd Bruise Size Needle length (mm) Injection volume (U) Bruising Bruise size (mm) N Yes, n (%) 3 (8.11) 4 (10.81) 4 (21.05) 5 (26.32) P vlue N Men SD P vlue (n) numer of ptients, (N) totl numer of ptients P vlues were clculted using the McNemr test P vlues were clculted using t-test Tle 4. Incidence of Bleeding Needle length (mm) Injection volume (U) Bleeding N Yes, n (%) 13 (10.48) 7 (5.83) 3 (4.92) 4 (6.56) P vlue P vlue.39 (N) totl numer of oservtions, (n) numer of oservtions Comprison of 20 U (5 mm vs 8 mm) nd 60 U (5 mm vs 8 mm). A GEE model ws used to clculte p vlues nd included the following fctors: needle length, injection site, nd injection sequence. Comprison of 5 mm needle (20 U + 60 U) versus 8 mm needle (20 U + 60 U). A GEE model ws used to clculte the p vlue nd included the following fctors: needle length, injection site, injection sequence, injection volume, nd spirin use. 392

5 ptients reported less leeding with the 5 mm needle nd less insulin lekge with the 8 mm needle, we found no differences etween the needle lengths with respect to leeding nd lekge. There re some importnt design differences etween the Kreugel study nd the present study, which my explin the different results. Ptients in the Kreugel study dministered their own injections, wheres ll injections were dministered y the investigtor in the present study. The mjority of endpoints in the Kreugel study, including lekge nd leeding, were ptient-reported. In contrst, lekge ws mesured nd leeding ws recorded y the investigtor in the present study. A unique feture of this study design ws the use of two different injections volumes given with oth needle lengths for ll endpoints. A single injection volume ws used in two reported studies. 5,6 Injection volumes vry depending on dose of insulin required. The injection volumes [20 U (200 μl) nd 60 U (600 μl) equivlent] used in this study were representtive of reltively lrge meltime dose of insulin nd the mximum dose of severl insulin pen injectors. A potentil limittion of this study is tht ll injections were investigtor-dministered. While linding ws necessry for ssessment of pin scores, the study design did not replicte rel life, in which most insulin injections re self-dministered. The ssessment of pin, where ptients were linded to needle length, my not ccurtely reflect the psychologicl perception of injection discomfort s compred with self-dministered injection. Another limittion of the present study ws tht glycemic endpoints were not exmined. Finlly, ll pen injections were rndomized to the left nd right lower qudrnts of the dominl re. The exclusion of other injection sites limits the conclusions of this study. Conclusion In summry, the 5 mm needle ws similr to the 8 mm needle with respect to insulin diluent lekge postinjection in oese ptients with type 1 or type 2 dietes. In ddition, the 5 mm needle ws similr to the 8 mm needle with respect to pin intensity, leeding, nd ruising t injection sites with 20 U (200 μl) or 60 U (600 μl) equivlent volumes. The results of this study provide further evidence supporting the suitility of the 5 mm needle for the injection of insulin in oese ptients with dietes. Funding: This study ws funded y Eli Lilly nd Compny. Acknowledgements: The uthors wish to cknowledge Michelle Crey, Ph.D., nd Joseph Durrnt, B.A., of i3 Sttproe for providing writing nd editoril ssistnce. Disclosures: Hod Fu nd Der re employees nd stockholders of Eli Lilly nd Compny. References: 1. Polonsky WH, Jckson RA. Wht s So Tough Aout Tking Insulin? Addressing the Prolem of Psychologicl Insulin Resistnce in Type 2 Dietes. Clin Dietes. 2004;22(3): Schwrtz S, Hssmn D, Shelmet J, Sievers R, Weinstein R, Ling J, Lyness W. A multicenter, open-lel, rndomized, two-period crossover tril compring glycemic control, stisfction, nd preference chieved with 31 guge x 6 mm needle versus 29 guge x 12.7 mm needle in oese ptients with dietes mellitus. Clin Ther. 2004;26(10): Frid A, Hirsch L, Gspr R, Hicks D, Kreugel G, Liersch J, Letondeur C, Suvnet JP, Tuin-Rufi N, Struss K; Scientific Advisory Bord for the Third Injection Technique Workshop. New injection recommendtions for ptients with dietes. Dietes Met. 2010;36 Suppl 2:S Struss K, Hnnet I, McGonigle J, Prkes JL, Ginserg B, Jml R, Frid A. Ultr-short (5 mm) insulin needles: Tril results nd clinicl recommendtions. Prct Dietes Int. 1999;16(7): Kreugel G, Keers JC, Jongloed A, Verweij-Gjltem AH, Wolffenuttel BHR. The Influence of Needle Length on Glycemic Control nd Ptient Preference in Oese Dietic Ptients [strct 440-P]. Dietes. 2009;58 Suppl Ross SA, Jml R, Leiter LA, Josse RG, Prkes JL, Qu S, Kerestn SP, Ginserg BH. Evlution of 8 mm insulin pen needles in people with type 1 nd type 2 dietes. Prct Dietes Int. 1999;16(5): Frrr JT, Young JP Jr, LMoreux L, Werth JL, Poole RM. Clinicl importnce of chnges in chronic pin intensity mesured on n 11-point numericl pin rting scle. Pin. 2001;94(2): Hrdy JD, Wolff HG, Goodell H. Pin Senstions nd Rections. Bltimore: Willims & Wilkins; Jensen MP, Turner JA, Romno JM. Wht is the mximum numer of levels needed in pin intensity mesurement? Pin. 1994;58(3): Jensen MP, Miller L, Fisher LD. Assessment of pin during medicl procedures: comprison of three scles. Clin J Pin. 1998;14(4): Peters ML, Ptijn J, Lmé I. Pin ssessment in younger nd older pin ptients: psychometric properties nd ptient preference of five commonly used mesures of pin intensity. Pin Med. 2007;8(7):