A cukorbetegség terápiája szisztematikus irodalmi áttekintés

A cukorbetegség terápiája szisztematikus irodalmi áttekintés Egy adott betegség terápiájának vizsgálatakor érdemes először a nemzetközi irodalmat áttekinteni, hogy bemutathassuk, milyen már meglévő eredmények, bizonyítékok állnak rendelkezésünkre. A cukorbetegség esetében több terápia közül vizsgálata közül választhatunk, amelyek összetettségükben és költségükben (és a költségek finanszírozójában) eltérnek egymástól. 1. Módszerek A szisztematikus irodalmi áttekintés fontos szerepet játszik a bizonyítékokon alapuló orvoslásban, mivel a már létező vizsgálati eredmények szigorú és formalizált összefoglalásával szolgáltat erős bizonyítékokat a páciens hatékony kezeléséhez, így segítve az eligazodást a gyakra szerteágazó eredmények között. A már létező eredmények és tudományos bizonyítékok feltárásához a ScienceDirect adatbázis keresőjét használtam. A keresés területe a cikk címe, keresési kulcsszava vagy témaköre volt. A túl nagy számú találat miatt a keresést tovább kellett szűkítenem a táblázatban látható módon. Nr. Kereső-kifejezés Szűkítés Találatok száma 1. diabetes NA 386.681 2. diabetes mellitus NA 171.489 3. diabetes mellitus 2000-present 114.956 4. Search #3 AND insulin 2000-present 51.596 5. Search #4 AND insulin detemir 2000-present 269 6. Search #5 AND insulin NPH 2000-present 79 7. Search #6 2000-present, full text 51 Keresés dátuma: 2010. október 5. A keresés eredményei az ELTE IP tartományában értelmezhetők. A diabetes mellitus keresőszavakra kapott eredményeket először keletkezésük éve szerint szűrtem (2000-napjainkig). A keresés elvégzése során ezután a cukorbetegség inzulinos kezelésére fókuszáltam, kiválasztva egy analóg (detemir)- és egy humán inzulinos (NPH) terápiát. Végül pedig, a jó interpretálhatóság követelményeit is szem előtt tartva, csak a teljes terjedelmükben elérhető cikkekre terjesztettem ki a keresést. Azért esett a választásom a két lehetséges inzulinos terápiára, mert ezeknek a költségei finanszírozói szempontból könnyen vizsgálhatóak (ellentétben pl. a speciális diétával), valamint lhetőség nyílik egy izgalmasabb, régi-új típusú összevetésre. 1

2. Eredmények A feladat leírásának megfelelően a következő táblázatban bemutatásra kerül a talált cikkek listája, legfontosabb megállapításuk, és a későbbi munkám könnyítése érdekében, azok gyorsértékelése minőségük alapján. A vizsgált cikkekkel kapcsolatos alapvető követelmények Hatóanyag Insulin Detemirt és/vagy Neutral Protamine Hagedorn Insulint vizsgál 18 év feletti, diagnosztizált 1-es vagy 2-es típusú diabetes mellitusos személy Betegpopuláció Nem: bármely; Rassz: bármely Nyelvi korlátozás Angol nyelvű cikk HbA(1c) szint, FPG szint, FBG szint, BMI érték, Testtömeg kg, dozírozás közül Vizsgált végpontok legalább kettő RCT, meta-analízis, review, retrospektív adatelemzés (persze az elemzés Vizsgálat típusa céljától függően), de semmiképpen sem esettanulmány, farmakokinetika, farmakodinamika, történeti áttekintés, vélemény. 2

Nr. Szerző Év Cím 1. Martin J. Abrahamson 2010. 2. 3. 4. Sonika Bhatnagar, Deepa Srivastava, M.S.K. Jayadev, A.K. Dubey G.B. Bolli, M. Songini, M. Trovati, S. Del Prato, G. Ghirlanda, R. Cordera, R. Trevisan, G. Riccardi, C. Noacco Bijan J. Borah, PhD; Theodore Darkow, PharmD; Jonathan Bouchard, MS; Mark Aagren, MSc; Felicia Forma, BSc; Berhanu Alemayehu, DrPHs 2006. 2009. 2009. 5. Julia M. Bottomley, Frank D. Raymond 2007. 6. P Kurtzhals 2005. Basal insulins: Pharmacological properties and patient perspectives Molecular variants and derivatives of insulin for improved glycemic control in diabetes Lower fasting blood glucose, glucose variability and nocturnal hypoglycaemia with glargine vs NPH basal insulin in subjects with Type 1 diabetes A Comparison of Insulin Use, Glycemic Control, and Health Care Costs With Insulin Detemir and Insulin Glargine in Insulin-Naive Patients With Type 2 Diabetes Pharmaco-economic issues for diabetes therapy How to achieve a predictable basal insulin? Karok / study design Összefoglaló jellegű Összefoglaló jellegű Glargine vs. NPH, 30 hetes. randomizált, párhuzamos Retrospektív, 2006 május 1-2006 december 31-ig, USA Szisztematikus irodalmi áttekintés, költséghatékonys ági elemzés Összefoglaló jellegű cikk Legfontosabb megállapítás In patients with type 2 diabetes, both insulin detemir and insulin glargine demonstrated a similar reduction in HbA1c levels and 24-hour glycaemic control, and lower risk of hypoglycaemia compared with insulin NPH, thereby confirming their appropriateness as an improved basal insulin, and supporting once-daily dosing of both agents in these patients. A review of molecular variants of insulin shows that correlating sequence, structure and activity profiles of insulin and its mutants in different species has led to many advances. The results indicate that, regarding the primary goal, glargine resulted in greater lowering of FBG by the end of study vs NPH. However, patients receiving insulin detemir incurred lower diabetes-related medical and total health care costs. During 2006, diabetes treatments were the second largest contributor to prescription drug spends, trailing only cholesterol-reducing drugs. Taken together, insulin detemir provides an attractive novel approach for predictive basal insulin delivery to people with diabetes. Gyorsértékelés Kevésbé részletes, inkább horizontális ismereteket nyújt. Nem használható, inkább gyógyszerészeknek szóló. Egyes részletek jól használhatók. Jól használható, de tekintettel kell lenni a lokális sajátosságokra. Jól használható QALY adatok, használható költségadatok Néhány biológiai adat használható. 3

7. Susan S. Braithwaite 2006. 8. Susan S. Braithwaite, Beverly Robertson, Hetal P. Mehrota, Linda M.MCelveen, Cara L.Thompson, 2007. 9. A. Enrique Caballero 2009. 10. Elaine Cochran, Phillip Gorden 2008. The Transition from Insulin Infusions to Long-Term Diabetes Therapy: The Argument for Insulin Analogs Managing Hyperglycemia in Hospitalized Patients Long-term benefits of insulin therapy and glycemic control in overweight and obese adults with type 2 diabetes Use of U-500 Insulin in the Treatment of Severe Insulin Resistance Szerzői véleményt tükröző,több cikket vizsgáló tanulmány Összefoglaló jellegű cikk, orvos-szakmai, egészségpolitikai szempotból lehet érdekes Szisztematikus irodalmi áttekintés Egykaros vizsgálat, dozírozási algoritmus tesztelésére (NPH) This review will present opinion on optimal use of insulin at the time of transitioning from intravenous insulin to subcutaneous insulin after heart surgery and on management options at the time of discharge. It is necessary to begin, however, with an admonition against use of sliding scale insulin. The evolution of IV insulin protocols, the development of standardized order sets and computerized order entry templates for SC insulin management, and the implementation of a diabetes hospital patient self-management program require interdisciplinary effort. Implementation of comprehensive treatment regimens that emphasize physical activity and exercise, and the more aggressive use of pharmacological agents to achieve tight glycemic control may offer the most promise for reducing mortality and for improving long-term clinical outcomes in obese patients with type 2 diabetes. The algorithm presented in this article reflects our experience in treating syndromic forms of insulin resistance and several cases of severe insulin resistance, obesity, and type 2 DM. A vélemény alacsony szintű bizonyíték, de a cikk néhány adata használható Alacsony relevanciájú Jól használható, alcsoportelemzésre fókuszált Túlspecifikált 11. George E. Dailey, MD 2006. Contributions of Fasting and Postprandial Plasma Glucose Levels to Glycosylated Hemoglobin and Diabetes Mellitus- Related Complications: Treating Hyperglycemia with Insulin Szisztematikus irodalmi áttekintés Early and persistent intensification of therapy designed to achieve glycemic goals, including the use of oral agents and/or insulin, should be initiated at diagnosis and appropriately titrated. The contributions of FPG and PPG to overall AIC should be closely monitored so that tile most appropriate and effective treatment regimen may be implemented. Hivatkozott adatok használhatók, dozírozásra fókuszált tanulmány 4

12. Stephen N. Davis 2007. 13. 14. Maria I. del Olmo, Vicente Campos, Pablo Abellan, Juan Francisco Merino- Torres, Francisco Pinon Satish K. Garg, Peter A. Gottlieb, Mary E. Hisatomi, Anna D Souza, Andrew J. Walker c, Kenneth E. Izuora, H. Peter Chase 2008. 2004. 15. Satish K. Garg, Heather Ulrich 2006. 16. H Gin, H Hanaire-Broutin 2005. Management of Type 2 Diabetes Mellitus with BasaI-Prandial Insulin Therapy: A Case-Based Review A case of lipoatrophy with insulin detemir Improved glycemic control without an increase in sever hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine Achieving Goal Glycosylated Hemoglobin Levels in Type 2 Diabetes Mellitus: Practical Strategies for Success with Insul,n Therapy Reproducibility and variability in the action of injected insulin Esettanulmány Esettanulmány Retrospektív, glargine/nph Szisztematikus irodalmi áttekintés Farmakokinetikai és farmakodinamikai vizsgálat Such a therapeutic approach obviates the risk for uncontrolled hyperglycemia, which is associated with the standard practice of beginning treatment with diet and exercise alone and slowly advancing by 1 OAD at a time, ending with insulin therapy as a last resort. Reports have been made on rapid insulin analogues, human insulin, CSII and even long acting insulin such as glargine. To our understanding, this is one of the first reported cases of lipoatrophy induced by insulin detemir. In summary, glycemic control improved significantly during glargine treatment without any increase in hypoglycemic episodes in the total group. For patients with type 2 DM, every effort must be made to continue achieving target AIC goals, with frequent blood glucose monitoring in conjunction with oral therapy plus basal and bolus multiple daily injection regimens, BID mixed insulins, or the use of an insulin pump. Nevertheless, the greatest element of variability in insulin resorption appears to be the patients quality of life and compliance to treatment. Túlspecifikált Túlspecifikált Részben használható, de tekintettel kell lenni a lokális sajátosságokra Kevéssé használható, inkább egészségpolitikai jellegű Minimálisan használható 5

17. Francisco J. Gomez-Perez, Juan A. Rull 2005. 18. Stephen C.L. Gough 2007. 19. B Guerci, JP Sauvanet 2005. 20. 21. Jens Gundgaard, Torsten E. Christensen, Trine Lyager Thomsen Simon Heller, Plamen Kozlovski, Peter Kurtzhals 2010. 2007. Insulin Therapy: Current Alternatives A review of human and analogue insulin trials Subcutaneous insulin: pharmacokinetic variability and glycemic variability Direct healthcare costs of patients with type 2 diabetes using longacting insulin analogues or NPH insulin in a basal insulin-only regimen Insulin s 85th anniversary An enduring medical miracle Review jellegű Review jellegű, detemir/glargine vs. NPH Farmakokinetika Retrospektív költségvizsgálat (2005), detemir/glargine vs. NPH Történeti áttekintés jellegű The most promising appears to be inhaled insulin according to studies demonstrating excellent control, apparently without significant side effects, although in relatively short-term trials. Longerterm studies to assure the safety are still necessary before recommending its extended use. This is an extensive, up-to-date review of recent advances in insulin therapy. Whilst the benefits on individual metabolic and clinical outcomes appear modest, almost all studies report some advantage when using insulin analogues in type 1 and type 2 diabetes. Significant benefits, including PPG lowering with the rapidacting analogues and the potential for reduction in cardiovascular risk, should be investigated further. The main pharmacokinetic and pharmacodynamic characteristics of these new insulin analogs are presented and discussed in the light of there intraand inter-individual variability. Their reduced variability should permit to reinforce near physiological insulin regimen such as basalbolus technique and to consider new approaches and therapeutic strategies in type 1 and type 2 diabetic patients. There was no difference in direct healthcare costs between patients using LAIAs or NPH insulin. Since the discovery of insulin, a number of advances have been made to allow patients to mimic the normal pattern of insulin release more accurately and conveniently. However, insulin therapy needs to improve still further to allow near normalization of blood glucose with a low risk of hypoglycaemia and weight gain. Minimálisan használható Nagyon jól használható klinikai adatok Kevéssé használható Megkötésekkel, de jól használható költségadatok Alig használható 6

22. 23. 24. 25. Simon Heller, MD; Christoph Koenen, MD, MBA, Bruce Bode, MD Priscilla Hollander, MD; John Cooper, MD; Jesper Bregnhoj, MD; and Claus Bang Pedersen, MSc P.D. Home, P. Hallgren, K.H. Usadel, T. Sane, J. Faber, V. Grill, H.H. Friberg Liza L. Ilag, MD; Lisa Kerr, MSPH;James K. Malone, MD; Meng H. Tan, MD 2009. 2008. 2006. 2007. Comparison of Insulin Detemir and Insulin Glargine in a Basal Bolus Regimen, With Insulin Aspart as the Mealtime Insulin, in Patients With Type 1 Diabetes: A 52-Week, Multinational, Randomized, Open- Label, Parallel-Group, Treat-to-Target Noninferiority Trial A 52-Week, Multinational, Open- Label, Parallel-Group, Noninferiority, Treatto-Target Trial Comparing Insulin Detemir with Insulin Glargine in a Basal- Bolus Regimen with Mealtime Insulin Aspart in Patients with Type 2 Diabetes Pre-meal insulin aspart compared with premeal soluble human insulin in type 1 diabetes Prandial Premixed Insulin Analogue Regimens Versus Basal Insulin Analogue Regimens in the Management of Type 2 Diabetes: An Evidence- Based Comparison 52-week, openlabel, parallelgroup, treat-to-target trial, detemir vs. glargine 52-week, openlabel, parallelgroup, treat-to-target trial, detemir vs. glargine 30-month, openlabel, parallel; insulin aspart vs. NPH Review jellegű In these patients with T1DM who were previously receiving basal bolus insulin therapy, detemir was noninferior to glargine in terms of the primary end point (HbA1c at 52 weeks), with no significant differences on most secondary end points. When used as indicated as part of a basal-bolus regimen in patients with T2DM who had previously received other insulin and/or OAD regimens, detemir was noninferior to glargine in its effects on overall glycemic control. The improvement in the first 6-month study in overall blood glucose control was maintained with insulin aspart, with a small but statistically significant difference in HbA1c but with a small, significantly increased rate of minor hypoglycaemic episodes. The results of this systematic review suggest that regimens consisting of prandial premixed insulin analogues, which provide both basal and prandial insulin coverage, may be used as an initial insulin regimen in patients with T2D to enable better overall, preprandial, and postprandial glycemic control compared with a basal insulin analogue regimen alone. Jó minőségű, valamelyest használható klinikai adatok Az előzővel meglepően jól kiegészítik egymást Kevéssé használható, de jó minőségű klinikai adatok Kevéssé használható, másképp fókuszált 7

26. György Jermendy 2006. Optimal insulin treatment for patients with type 2 diabetes Basal or prandial insulin supplementation? Vitaindító jellegű Instead of the question whether basal or prandial insulin supplementation is more critical, the mode of treatment providing appropriate basal and prandial insulin supplementation is of importance. Kevéssé használható, másképp fókuszált 27. Azuma Kanatsuka, Koichi Kawai, Koichi Hirao, Mariko Oishi, Hirofumi Takagi, Masashi Kobayashi 2006. Actual usage and clinical effectiveness of insulin preparations in patients with Type 1 diabetes mellitus in Japan: CoDiC-based analysis of clinical data obtained at multiple institutions Retrospektív vizsgálat In summary, intensive insulin therapy is actively performed and the rapid-acting insulin analogues are widely used in Type 1 diabetic patients in Japan. Túlspecifikált 28. E. Larger 2005. Weight gain and insulin treatment Review-jellegű, detemir vs. NPH vs. glargine Data obtained in the recent years have confirmed the idea that most of the weight gain observed when HbA1c is significantly reduced with insulin, both in type 1 and type 2 diabetic patients, is a catch-up weight re-gain. Egyes klinikai adatok kiválóan használhatók 29. David C.W. Lau 2010. Diabetes and weight management Eredmény-leírás szerű, review jellegű cikk, detemir vs. NPH vs. glargine Insulin detemir is a basal insulin analogue that improves glycaemic control and is associated with less hypoglycaemia than insulin NPH; it also causes less weight gain compared with insulin NPH. Egyes klinikai adatok kiválóan használhatók 30. Sandra Lea, Richard N. Herrier, Marisa Soto 2006. The Role of Rapid- Acting Insulin Analogues and Inhaled Insulin in Type 2 Diabetes Mellitus Review jellegű, humán inzulin vs. inhalált inzulin Although rapid-acting insulin analogues are effective in the management of patients with type 2 DM, the limited numbers of studies have yet to demonstrate that these agents have any significant long-term advantage compared with RHI. Kevéssé használható 31. Andreas Liebl, Guy Rutten, Carlos Abraira 2010. Treat early, treat appropriately Review, egészségpolitikai jellegű Future changes in the management of type 2 diabetes will shift the emphasis of care away from the secondary setting towards primary care. Más fókusz, bár jól használható 8

32. RobertJ. Ligthelm, MD; Vito Borzi, PhD;Janusz Gumprecht, MD, PhD; Ryuzo Kawamori, MD; Yang Wenying, MDS; Paul Valensi, MD 2007. 33. Michael A. Magnolti, Elliot J. Rayfield 2007. 34. 35. E. Mandosi, M. Fallarino, M. Rossetti, A. Gatti, S. Morano M. Marre, M. Pinget, H. Ginc, C. Thivolet, H. Hanaire, J.-J. Robert, P. Fontaine 2009. 2009. Importance of Observational Studies in Clinical Practice An Update on Insulin Injection Devices Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVETM study in a cohort of French patients with type 1 or type 2 diabetes Review, epidemiológiailag releváns Review Egykaros vizsgálat, eredmény-leírás szerű 52 week, cohort study, France Well-designed observational studies can play a key role in supporting the evidence base for drugs and therapies. Current evidence suggests that observational studies can be conducted using the same exacting and rigorous standards as are used for RCTs. The observational study design should be considered as a complementary rather than a rival analytic technique. Insulin pens provide DM patients with a number of advantages over a vial and syringe and can often help them overcome major barriers to the initiation of insulin therapy. The use of insulin pens leads to increased patient compliance and potential improvements in glycosylated hemoglobin, but data on glycemic control are not available. In this study we demonstrated that type 2 diabetes patients switched from NPH to detemir had improved metabolic control and reduced waist circumference after 20 weeks. Moreover patients reported an improvement in treatment satisfaction using the standardised DTSQ. Patients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline. Módszertanilag kitűnő, de kevéssé használható Gyógyászati segédeszközöket vizsgál, nem releváns Enyhén túlspecifikált, de jelen feladat esetében használható Kiváló minőségű adatok 36. Luigi Meneghini, Andreas Liebl, Martin J. Abrahamson 2010. Insulin detemir: A historical perspective on a modern basal insulin analogue Történeti jellegű áttekintő In particular, detemir may pave the way for the development of analogues that have even more physiologic profiles with regard to prolonged and reproducible action, and the avoidance of hypoglycaemia and weight gain. Más fókusz, kevéssé releváns 9

37. 38. 39. 40. 41. Matteo Monami, Niccolo Marchionni, Edoardo Mannucci Massimo Motta, Ettore Bennati, Laura Ferlito, Michela Passamonte, Elisabeth Cardillo, Mariano Malaguarnera Athena Philis-Tsimikas, MD; Guillaume Charpentier, MD; Per Clauson, MD, PhD; Gabriela Martinez Ravn, MSc; Victor Lawrence Roberts, MD; Birger Thorsteinsson, MD Dennis J. Pillion, Michael D. Fyrberg, Elias Meezan K. Rašlová, M. Bogoev, I. Raz, G. Leth, M-A. Gall, N. Hancu 2008. 2008. 2006. 2010. 2004. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes. A metaanalysis A review on the actual trends of insulin treatment in elderly with diabetes Comparison of Once- Daily Insulin Detemir with NPH Insulin Added to a Regimen of Oral Antidiabetic Drugs in Poorly Controlled Type 2 Diabetes Nasal absorption of mixtures of fast-acting and long-acting insulins Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes Meta-analízis >1 RCT alapján Review, történeti jellegű áttekintés RCT, evening detemir vs. morning detemir vs. NPH Farmakokinetika Randomizált, parralel, openlabel; detemir+asp vs. NPH+HSI Long-acting insulin analogues in type 2 diabetic patients does not seem to provide a better glycemic control in comparison with NPH insulin, whereas it reduces the risk of nocturnal and symptomatic hypoglycemia. Detemir, but not glargine, could be associated with smaller weight gain than NPH insulin. The choice of therapeutic strategy to be applied in the elderly diabetics should be based on a multidimensional assessment of the actual state of the patients, such as poor economic-social-sanitary conditions, sedentariety, malnutrition, presence of neoplastic diseases, alcoholism, smoking, etc., and the specific geriatric ones, like the polypathologies, frailty, disabilities, generalized or localized alterations of atherosclerosis, etc. The results of this study in patients whose type 2 DM was poorly controlled with _>10AD suggest that insulin detemir QD in the morning or evening can be used to improve glycemic control. The pharmacokinetic and pharmacodynamic profiles of the insulin mixtures reflected the additive contributions of both the rapid-acting and the long-acting insulins. These results support the possibility of formulating certain insulin mixtures in tandem to provide nasal insulin products that match the needs of patients with diabetes mellitus better than those currently available. Basal-bolus treatment with IDet + IAsp is an effective and well tolerated insulin regimen in people with type 2 diabetes, resulting in glycaemic control comparable to that of NPH + HSI, but with the advantages of less weight gain and a lower day-to-day within-person variation in FPG. Kiváló minőségű klinikai adat és bizonyíték Más fókusz, alacsony relevancia Jó minőségű klinikai adatok Nem releváns Jó minőségű, feltételekkel használható adatok 10

42. Susan Renda 2006. How to Adjust Your Insulin Dosages Patient handout Nem releváns Nem releváns 43. Marc S. Rendell, Lois Jovanovic 2006. 44. Carolyn Robertson 2008. 45. David Russell-Jones, MD, FRCP, Richard Simpson, MD, Birgitte Hylleberg, MSc, Eberhard Draeger, PhD, Jan Bolinder, MD, PhD 2004. Targeting postprandial hyperglycemia Translating ADA/EASD Guidelines and the ACE/AACE Road Maps into Primary Care of Patients with Type 2 Diabetes Effects of QD Insulin Detemir or Neutral Protamine Hagedorn on Blood Glucose Control in Patients with Type 1 Diabetes Mellitus Using a Basal-Bolus Regimen Történeti áttekintő, ajánlás Review 6-month, prospective, randomized, open-label, controlled, parallel-group trial, detemir vs. NPH It is recognized that elevation of plasma glucose is detrimental. Numerous studies have demonstrated that lowering HbA1c reduces the incidence of microvascular disease and diabetic neuropathy. However, HbA1c reflects the mean plasma glucose over a prolonged period. It has now been recognized that the transient rise in blood glucose, which occurs after a meal, may have very specific deleterious effects on blood vessels. There is a marked increase in cardiovascular risk in individuals with postprandial hyperglycemia. In this review, the cases described reveal a pathway of diabetes treatment that is advocated by the guidelines.this pathway should be communicated to patients through educational strategies. In this study, QD administration of insulin detemir at bedtime resulted in lower fasting blood glucose levels with less day-to-day variability and less fluctuation from mean blood glucose levels over 24 hours than NPH insulin, combined with an overall reduction in the risk of nocturnal hypoglycemia. These findings suggest that evening administration of insulin detemir may provide an opportunity to further improve fasting blood glucose targets. Nem releváns Minimális relevancia Jó minőségű klinikai adatok 11

46. A. Sola, E. Larger, J. M Bemba, F. Elgrably, G. Slama 2006. 47. Sanne G.H.A. Swinnen, J. Hans DeVries 2009. 48. P Valensi, E Cosson 2005. New insulins: interests and convenients Higher dose requirements with insulin detemir in type 2 diabetes Three cases and a review of the literature Is insulin detemir able to favor a lower variability in the action of injected insulin in diabetic subjects? Faramkokinetika Esettanulmány és review Farmakokinetika A new educational method, called functional insulin treatment, makes it possible, amongst other things, to give the keys to the patients using basal-bolus insulin regimen to adjust the amount of fast-acting insulin to variable quantities of glucids at the price of intensive self-monitoring of blood glucose levels. Regardless of the explanation, clinicians should be aware of potentially increased insulin dose requirements when prescribing insulin detemir to their type 2 diabetic patients. The variability in insulin resorption alters the confidence of the patients in their treatment. It may also alter their quality of life and compliance to treatment. The above summarized studies provide altogether evidence for a better reproducibility in the action of insulin detemir as compared with other basal insulins. Nem releváns, francia nyelven íródott Hivatkozott klinikai adatok használhatók Nem releváns 49. Patrick Vlieghe, Vincent Lisowski, Jean Martinez and Michel Khrestchatisky 2010. Synthetic therapeutic peptides: science and market Piacelemzés We are convinced that chronic treatment with new formulations or routes of administration will give a new impetus to the therapeutic peptide field. K+F adatok használhatók 50. Tsutomu Wada, Mari Azegami, Maine Sugiyama, Hiroshi Tsuneki, Toshiyasu Sasaoka 2008. Characteristics of signalling properties mediated by longacting insulin analogue glargine and detemir in target cells of insulin Farmakokinetika In conclusion, we have demonstrated that metabolic and mitogenic effects of glargine were quantitatively similar to that of human insulin in target cultured cells, inferring that this analogue shares a common mechanism of action to the natural hormone. Nem releváns 12

51. Fei Wang, MSc, PharmD, Jana M. Carabino, PharmD, Cunegundo M. Vergara, MD, FACP 2003. Insulin Glargine: A Systematic Review of a Long-Acting Insulin Analogue review, glargine vs. NPH As a basal insulin replacement, insulin glargine administered once daily demonstrates a steady time-action profile over 24 hours without a pronounced peak. Based on the evidence from published clinical trials, insulin glargine appears to have equal clinical efficacy to NPH insulin, produces similar reductions in HhArc, and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes. Részben releváns, de jó minőségű adatok *A jó minőségű bizonyítékokat, adatokat zöld színnel jelöltem A korábban bemutatott alapvető kritériumok alapján 5 jó minőségű tanulmányt sikerült kiválasztani. 13

3. Összegzés, észrevételek A szisztematikus irodalmi áttekintés a technológiaelemzés kezdeti folyamatában játszik szerepet. Ahhoz, hogy egy adott technológiát a finanszírozó (és jó esetben az igénybevevő, valamint a szolgáltató) számára döntési alternatívaként kínáljunk fel, valamilyen módon összegeznünk kell a vele kapcsolatban felmerült tapasztalatokat. Ennek elméleti háttere az egészségügyi piac sajátosságaiban rejlik: többek között a tökéletes informáltság feltétele sem áll fent. A szisztematikus irodalmi áttekintés ennek a problémának a feloldásában nyújthat segítséget, persze csak akkor, ha az áttekintés készítője sem elfogult. Gyakorlati szempontból vizsgálva a módszert, a befogadói döntéshozatal alkalmával az egyik leggyakrabban alkalmazott módszer a modellezés, ami számára a szisztematikus irodalmi áttekintés szállítja a szükséges input adatok egészségnyereségre vonatkozó részét. Az összegyűjtött tapasztalatokat azonban még rendszerezni kell, hogy használható formába (úgy, mint bizonyíték) kerüljenek. A kiválasztott tudományos bizonyítékokat érdemes kritikus értékelés alá vetni, így nagyban javíthatjuk a modellünk minőségét. Ezzel vissza is érkeztem dolgozatom kiindulópontjához, a bizonyítékokon alapuló orvosláshoz. A módszerrel kapcsolatos személyes észrevételem, hogy egy technológiáról rendelkezésre álló eredmények, bizonyítékok összegyűjtéséhez nem elégséges egyetelne adatbázis használata, mindenképpen ajánlott a lehető legtöbb releváns adatbázis áttekintése, szükségtől (és rendelkezésre álló időtől) függően indokolt lehet szabadkereséses hólabda -módszer alkalmazása is. 14

A feladatban bemutatott tanulmányok hivatkozásai Martin J. Abrahamson, Basal insulins: Pharmacological properties and patient perspectives, Primary Care Diabetes, Volume 4, Supplement 1, Breaking down barriers to insulin management in primary care, April 2010, Pages S19-S23 Sonika Bhatnagar, Deepa Srivastava, M.S.K. Jayadev, A.K. Dubey, Molecular variants and derivatives of insulin for improved glycemic control in diabetes, Progress in Biophysics and Molecular Biology, Volume 91, Issue 3 G.B. Bolli, M. Songini, M. Trovati, S. Del Prato, G. Ghirlanda, R. Cordera, R. Trevisan, G. Riccardi, C. Noacco, Lower fasting blood glucose, glucose variability and nocturnal hypoglycaemia with glargine vs NPH basal insulin in subjects with Type 1 diabetes, Nutrition, Metabolism and Cardiovascular Diseases, Volume 19, Issue 8, October 2009, Pages 571-579 Bijan J. Borah, Theodore Darkow, Jonathan Bouchard, Mark Aagren, FeliciaForma, Berhanu Alemayehu, A comparison of insulin use, glycemic control, and health care costs with insulin detemir and insulin glargine in insulin-naive patients with type 2 diabetes, Clinical Therapeutics, Volume 31, Issue 3, March 2009, Pages 623-631 Julia M. Bottomley, Frank D. Raymond, Pharmaco-economic issues for diabetes therapy, Best Practice & Research Clinical Endocrinology & Metabolism, Volume 21, Issue 4, New Therapies for Diabetes, December 2007, Pages 657-685 P. Kurtzhals, How to achieve a predictable basal insulin?, Diabetes & Metabolism, Volume 31, Issue 4, Part 2, September 2005, Pages 4S25-4S33 Susan S. Braithwaite, The Transition from Insulin Infusions to Long-Term Diabetes Therapy: The Argument for Insulin Analogs, Seminars in Thoracic and Cardiovascular Surgery, Volume 18, Issue 4, Diabetes, Hyperglycemia, and the Cardiac Surgery Patient, Winter 2006, Pages 366-378 Susan S. Braithwaite, Hetal P. Mehrotra, Beverly Robertson, Linda M. McElveen, Cara L. Thompson, Managing Hyperglycemia in Hospitalized Patients, Clinical Cornerstone, Volume 8, Issue 2, 2007, Pages 44-57 A. Enrique Caballero, Long-term benefits of insulin therapy and glycemic control in overweight and obese adults with type 2 diabetes, Journal of Diabetes and its Complications, Volume 23, Issue 2, March-April 2009, Pages 143-152 Elaine Cochran, Phillip Gorden, Use of U-500 insulin in the treatment of severe insulin resistance, Insulin, Volume 3, Issue 4, October 2008, Pages 211-218 George E. Dailey, Contributions of fasting and postprandial plasma glucose levels to glycosylated hemoglobin and diabetes mellitusrelated complications: Treating hyperglycemia with insulin, Insulin, Volume 1, Issue 4, October 2006, Pages 148-157 Stephen N. Davis, Management of Type 2 Diabetes Mellitus with Basal-Prandial Insulin Therapy: A Case-Based Review, Insulin, Volume 2, Issue 3, July 2007, Pages 118-126 Maria I. del Olmo, Vicente Campos, Pablo Abellan, Juan Francisco Merino-Torres, Francisco Pinon, A case of lipoatrophy with insulin detemir, Diabetes Research and Clinical Practice, Volume 80, Issue 1, April 2008, Pages e20-e21 Satish K. Garg, Peter A. Gottlieb, Mary E. Hisatomi, Anna D'Souza, Andrew J. Walker, Kenneth E. Izuora, H.Peter Chase, Improved glycemic control without an increase in severe hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine, Diabetes Research and Clinical Practice, Volume 66, Issue 1, October 2004, Pages 49-56 Satish K. Garg, Heather Ulrich, Achieving goal glycosylated hemoglobin levels in type 2 diabetes mellitus: Practical strategies for success with insulin therapy, Insulin, Volume 1, Issue 3, July 2006, Pages 109-121 H Gin, H Hanaire-Broutin, Reproducibility and variability in the action of injected insulin, Diabetes & Metabolism, Volume 31, Issue 1, February 2005, Pages 7-13 Francisco J. Gomez-Perez, Juan A. Rull, Insulin Therapy: Current Alternatives, Archives of Medical Research, Volume 36, Issue 3, Current Trends in Diabetes, May-June 2005, Pages 258-272 Stephen C.L. Gough, A review of human and analogue insulin trials, Diabetes Research and Clinical Practice, Volume 77, Issue 1, July 2007, Pages 1-15 15

B. Guerci, J.P. Sauvanet, Subcutaneous insulin: pharmacokinetic variability and glycemic variability, Diabetes & Metabolism, Volume 31, Issue 4, Part 2, September 2005, Pages 4S7-4S24 Jens Gundgaard, Torsten E. Christensen, Trine Lyager Thomsen, Direct healthcare costs of patients with type 2 diabetes using longacting insulin analogues or NPH insulin in a basal insulin-only regimen, Primary Care Diabetes, Volume 4, Issue 3, October 2010, Pages 165-172 Simon Heller, Plamen Kozlovski, Peter Kurtzhals, Insulin's 85th anniversary--an enduring medical miracle, Diabetes Research and Clinical Practice, Volume 78, Issue 2, November 2007, Pages 149-158 Simon Heller, Christoph Koenen, Bruce Bode, Comparison of insulin detemir and insulin glargine in a basal--bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: A 52-week, multinational, randomized, open-label, parallelgroup, Treat-to-Target noninferiority trial, Clinical Therapeutics, Volume 31, Issue 10, October 2009, Pages 2086-2097 Priscilla Hollander, John Cooper, Jesper Bregnhoj, Claus Bang Pedersen, A 52-week, multinational, open-label, parallel-group, noninferiority, treat-to-target trial comparing insulin detemir with insulin glargine in a basal-bolus regimen with mealtime insulin aspart in patients with type 2 diabetes, Clinical Therapeutics, Volume 30, Issue 11, November 2008, Pages 1976-1987 P.D. Home, P. Hallgren, K.H. Usadel, T. Sane, J. Faber, V. Grill, H.H. Friberg, Pre-meal insulin aspart compared with pre-meal soluble human insulin in type 1 diabetes, Diabetes Research and Clinical Practice, Volume 71, Issue 2, February 2006, Pages 131-139 Liza L. Ilag, Lisa Kerr, James K. Malone, Meng H. Tan, Prandial Premixed Insulin Analogue Regimens Versus Basal Insulin Analogue Regimens in the Management of Type 2 Diabetes: An Evidence-Based Comparison, Clinical Therapeutics, Volume 29, Issue 6, Part 1, 2007, Pages 1254-1270 Gyorgy Jermendy, Optimal insulin treatment for patients with type 2 diabetes: Basal or prandial insulin supplementation?, Diabetes Research and Clinical Practice, Volume 74, Issue 2, Supplement 1, Proceedings of the 5th Regional Medical Conference on the Treatment of Type 2 Diabetes Mellitus, 30 November 2006, Pages S20-S29 Azuma Kanatsuka, Koichi Kawai, Koichi Hirao, Mariko Oishi, Hirofumi Takagi, Masashi Kobayashi and Japan Diabetes Clinical Data Management Study Group: Actual usage and clinical effectiveness of insulin preparations in patients with Type 1 diabetes mellitus in Japan: CoDiC(R)-based analysis of clinical data obtained at multiple institutions (JDDM 3). Diabetes Research and Clinical Practice, Volume 72, Issue 3, June 2006, Pages 277-283 E. Larger, Weight gain and insulin treatment, Diabetes & Metabolism, Volume 31, Issue 4, Part 2, September 2005, Pages 4S51-4S56 David C.W. Lau, Diabetes and weight management, Primary Care Diabetes, Volume 4, Supplement 1, Breaking down barriers to insulin management in primary care, April 2010, Pages S24-S30 Sandra Leal, Richard N. Herrier, Marisa Soto, The role of rapid-acting insulin analogues and inhaled insulin in type 2 diabetes mellitus, Insulin, Volume 2, Issue 2, April 2007, Pages 61-67 Andreas Liebl, Guy Rutten, Carlos Abraira, Treat early, treat appropriately, Primary Care Diabetes, Volume 4, Supplement 1, Breaking down barriers to insulin management in primary care, April 2010, Pages S3-S10 Robert J. Ligthelm, Vito Borzi, Janusz Gumprecht, Ryuzo Kawamori, Yang Wenying, Paul Valensi, Importance of Observational Studies in Clinical Practice, Clinical Therapeutics, Volume 29, Issue 6, Part 1, 2007, Pages 1284-1292 Michael A. Magnolti, Elliot J. Rayfield, An Update on Insulin Injection Devices, Insulin, Volume 2, Issue 4, October 2007, Pages 173-181 E. Mandosi, M. Fallarino, M. Rossetti, A. Gatti, S. Morano, Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH, Diabetes Research and Clinical Practice, Volume 84, Issue 2, May 2009, Pages e18- e20 M. Marre, M. Pinget, H. Gin, C. Thivolet, H. Hanaire, J.-J. Robert, P. Fontaine, Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE(TM) study in a cohort of French patients with type 1 or type 2 diabetes, Diabetes & Metabolism, Volume 35, Issue 6, December 2009, Pages 469-475 16

Luigi Meneghini, Andreas Liebl, Martin J. Abrahamson, Insulin detemir: A historical perspective on a modern basal insulin analogue, Primary Care Diabetes, Volume 4, Supplement 1, Breaking down barriers to insulin management in primary care, April 2010, Pages S31-S42 Matteo Monami, Niccolo Marchionni, Edoardo Mannucci, Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: A meta-analysis, Diabetes Research and Clinical Practice, Volume 81, Issue 2, August 2008, Pages 184-189 Massimo Motta, Ettore Bennati, Laura Ferlito, Michela Passamonte, Elisabeth Cardillo, Mariano Malaguarnera, A review on the actual trends of insulin treatment in elderly with diabetes, Archives of Gerontology and Geriatrics, Volume 47, Issue 1, July-August 2008, Pages 151-161 Athena Philis-Tsimikas, Guillaume Charpentier, Per Clauson, Gabriela Martinez Ravn, Victor Lawrence Roberts, Birger Thorsteinsson, Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly Controlled Type 2 Diabetes, Clinical Therapeutics, Volume 28, Issue 10, October 2006, Pages 1569-1581 Dennis J. Pillion, Michael D. Fyrberg, Elias Meezan, Nasal absorption of mixtures of fast-acting and long-acting insulins, International Journal of Pharmaceutics, Volume 388, Issues 1-2, 30 March 2010, Pages 202-208 K. Raslova, M. Bogoev, I. Raz, G. Leth, M-A. Gall, N. Hancu, Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes, Diabetes Research and Clinical Practice, Volume 66, Issue 2, November 2004, Pages 193-201 Susan Renda, How to adjust your insulin dosages, Insulin, Volume 1, Issue 2, April 2006, Pages 81-82 Marc S. Rendell, Lois Jovanovic, Targeting postprandial hyperglycemia, Metabolism, Volume 55, Issue 9, September 2006, Pages 1263-1281 Carolyn Robertson, Translating ADA/EASD Guidelines and the ACE/AACE Road Maps into Primary Care of Patients with Type 2 Diabetes, The Journal for Nurse Practitioners, Volume 4, Issue 9, October 2008, Pages 661-671 David Russell-Jones, Richard Simpson, Birgitte Hylleberg, Eberhard Draeger, Jan Bolinder, Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen, Clinical Therapeutics, Volume 26, Issue 5, May 2004, Pages 724-736 A. Sola, E. Larger, J. M'Bemba, F. Elgrably, G. Slama, Les nouvelles insulines : interets et inconvenients, Reanimation, Volume 15, Issue 6, November 2006, Pages 454-460 Sanne G.H.A. Swinnen, J. Hans DeVries, Higher dose requirements with insulin detemir in type 2 diabetes--three cases and a review of the literature, Diabetes Research and Clinical Practice, Volume 84, Issue 2, May 2009, Pages e24-e26 P. Valensi, E. Cosson, Is insulin detemir able to favor a lower variability in the action of injected insulin in diabetic subjects?, Diabetes & Metabolism, Volume 31, Issue 4, Part 2, September 2005, Pages 4S34-4S39 Patrick Vlieghe, Vincent Lisowski, Jean Martinez, Michel Khrestchatisky, Synthetic therapeutic peptides: science and market, Drug Discovery Today, Volume 15, Issues 1-2, January 2010, Pages 40-56 Tsutomu Wada, Mari Azegami, Maine Sugiyama, Hiroshi Tsuneki, Toshiyasu Sasaoka, Characteristics of signalling properties mediated by long-acting insulin analogue glargine and detemir in target cells of insulin, Diabetes Research and Clinical Practice, Volume 81, Issue 3, September 2008, Pages 269-277 Fei Wang, Jana M. Carabino, Cunegundo M. Vergara, Insulin glargine: A systematic review of a long-acting insulin analogue, Clinical Therapeutics, Volume 25, Issue 6, June 2003, Pages 1541-1577 17