A glükagonszerű peptid-1 receptorának agonistái napjainkban a 2-es típusú diabetes vércukorcsökkentő kezelésének meghatározó készítményei. Mára kikristályosodtak adásuk lehetőségei: a fel- (step-up) és a leépítő (step-down), vagy elterjedt új keletű kifejezéssel, a deeszkalációs antidiabetikumkezelésben való részvételük, a már hozzáférhető oralis változatnak a parenteralis készítményformával szemben mutatkozó előnyei és potenciális hátrányai, valamint a bázisinzulinnal kombinált, fix összetételű változataik lehetséges differenciálási lehetőségei. E kérdéseket tekinti át munkánk, de kitér a gyógyszercsoporttal kapcsolatos újabb kutatásokra, a fejlesztés alatt álló új, részben kombinációs készítményekre is. Felhívja a figyelmet e csoport képviselői – elsősorban hosszú hatású származékai − korai alkalmazásának jelentőségére, cardiorenalis védőhatására és a még szélesebb körű használatuk érdekében szükséges folyamatos orvosszakmai tájékoztatás, valamint betegedukáció fontosságára. Orv Hetil. 2022; 163(29): 1144–1151.
Overgaard RV, Lindberg SØ, Thielke D, et al. Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: a model-based approach. Diabetes Obes Metab. 2019; 21: 43–51.
Ishigaki Y, Strizek A, Aranishi T, et al. Glucagon-like peptide-1 receptor agonist utilization in type 2 diabetes in Japan: a retrospective database analysis (JDDM 57). Diabetes Ther. 2021; 12: 345–361.
Trujillo JM, Nuffer W, Smith BA. GLP-1 receptor agonists: an updated review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2021; 12: 2042018821997320.
Zhao X, Wang M, Wen Z, et al. GLP-1 receptor agonists: beyond their pancreatic effects. Front Endocrinol. 2021; 12: 721135.
Dal Canto E, Ceriello A, Rydén L, et al. Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019; 26(2_Suppl): 25–32.
Winkler G. Complementer and additive effects – pathobiochemical background of cardiorenal advantages of GLP-1 receptor agonists and SGLT-2 inhibitors. [Komplementer és additív hatások – a GLP-1 receptoragonisták és az SGLT-2 gátlók kardiorenális előnyeinek patobiokémiai háttere.] Diabetol Hung. 2021; 29: 279–287. [Hungarian]
Buse JB, Wexler DJ, Tsapas A, et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia 2020; 63: 221–228. és Diabetes Care 2020; 43: 487–493 . Erratum: Diabetes Care 2020; 43: 1670.
Ministry of Human Resources health professional guidelines for the diagnosis of diabetes mellitus and the antihyperglycemic treatment and care of diabetics in adulthood. [Az Emberi Erőforrások Minisztériuma egészségügyi szakmai irányelve a diabetes mellitus kórismézéséről, a cukorbetegek antihyperglykaemiás kezeléséről és gondozásáról felnőttkorban.] Eü Közl. 2020; 70(12): 1759–1857. [Hungarian]
Quattrocchi E, Goldberg T, Marzella N. Management of type 2 diabetes: consensus of organizations. Drugs in Context. 2020; 9: 212607.
Cavallari I, Bhatt DL, Steg G, et al. Causes and risk factors for death in diabetes: a competing-risk analysis from the SAVOR-TIMI 53 trial. J Am Coll Cardiol. 2021; 77: 1837–1840.
Birkeland KI, Bodegard J, Eriksson JW, et al. Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes: a large multinational cohort study. Diabetes Obes Metab. 2020; 22: 1607–1618.
Nowakowska M, Zghebi SS, Aschcroft DM, et al. The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort. BMC Med. 2019; 17: 145. Erratum: BMC Med. 2020; 18: 22.
Holst JJ. Long-acting glucagon-like peptide-1 receptor agonists – status december 2018. Ann Transl Med. 2019; 7: 83.
Saraiva JF, Franco D. Oral GLP-1 analogue: perspectives and impact on athertosclerosis in type 2 diabetic patients. Cardiovasc Diabetol. 2021; 20: 235.
Home PD, Aroda VR, Blonde L, et al. Efficacy and safety of iGlarLixi versus IDegLira in adults with type 2 diabetes inadequately controlled by glucagon-like peptide-1 receptor agonists: a systematic literature review and indirect treatment comparison. Diabetes Obes Metab. 2020; 22: 2170–2178.
Evans M, Billings LK, Håkan-Bloch J, et al. An indirect treatment comparison of the efficacy of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) in patients wih type 2 diabetes uncontrolled on basal insulin. J Med Econ. 2018; 21: 340–347.
Winkler G. Oral or parenteral semaglutide. Aspects of their differentiated application. [Orális vagy parenterális szemaglutid. A differenciált alkalmazás szempontjai.] Háziov Továbbk Szle. 2021; 26: 262–267. [Hungarian]
Gallwitz B, Giorgino F. Clinical perspectives on the use of subcutaneous and oral formulations of semaglutide. Front Endocrinol. 2021; 12: 645507.
Overgaard RV, Hertz CL, Ingwersen SH, et al. Levels of circulating semaglutide determine reductions in HbA1c and body weight in people with type 2 diabetes. Cell Rep Med. 2021; 2: 100387.
Harris S, Abrahamson MJ, Ceriello A, et al. Clinical considerations when initiating and titrating insulin degludec/liraglutide (IDegLira) in people with type 2 diabetes. Drugs 2020; 80: 147–165.
Bolli GB, Porcellati F, Meier JJ. Switching from insulin bolus treatment to GLP-1 RAs added to continued basal insulin n people with type 2 diabetes on basal-bolus insulin. Diabetes Care 2020; 43: 2333–2335.
Rosenstock J, Nino A, Soffer J, et al. Impact of a weekly glucagon-like peptide-1 recepor agonist, albiglutide, on glycemic control and on reducing prandial insulin use in type 2 diabetes inadequately controlled on multiple insulin therapy: a randomized trial. Diabetes Care 2020; 43: 2509–2518. Comments and responses. Diabetes Care 2021; 44: e196–e197.
Boye KS, Stein D, Matza LS, et al. Timing of GLP-1 receptor agonist initiation for treatment of type 2 diabetes in the UK. Drugs RD 2019; 19: 213–225.
Morris D. GLP-1 receptor agonists in type 2 diabetes: an underused asset? J Diabetes Nurs. 2020, 24: JDN155.
Fadini GP, Frison V, Rigato M, et al. Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy. Acta Diabetol. 2020; 57: 367–375.
Kosiborod M, Aroda VR, Honore JB, et al. Trends in initiation of GLP-1 RA in patients with type 2 diabetes during 2014-2019: a US database study. Eur Heart J 2021; 42(Suppl 1): ehab724.2957.
Weiss T, Yang L, Carr RD, et al. Real-world weight change, adherence, and discontinuation among patients with type 2 diabetes initiating glucagon-like peptide-1 receptor agonists in the UK. BMJ Open Diabetes Res Care 2022; 10: e002517.
Khan SM, Fonarow GC, McGuire DK, et al. Glucagon-like peptide-1 receptor agonists and heart failure: the need for further evidence generation and practice guidelines optimization. Circulation 2020; 142: 1205–1218.
Giugliano D, Scappaticcio L, Longo M, et al. GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs. Cardiovasc Diabetol. 2021; 20: 189.
Grieco M, Giorgi A, Gentile MC, et al. Glucagon-like peptide-1: a focus on neurodegenerative diseases. Front Neurosci 2019; 13: 1112.
Angarita GA, Matuskey D, Pittman B, et al. Testing the effects of the GLP-1 receptor agonist exenatide on cocaine self administration and subjective responses in humans with cocaine use disorder. Drug Alcohol Depend. 2021; 221: 108614.
Zhu C, Li H, Kong X, et al. Possible mechanisms underlying the effects of glucagon-like peptide-1 receptor agonist on cocaine use disorder. Front Pharmacol. 2022; 13: 819470.
Wong C, Lee MH, Yaow CY, et al. Glucagon-like peptide-1 receptor agonists for non-alcoholic fatty liver disease in type 2 diabetes: a meta-analysis. Front Endocrinol 2021; 12: 609110.
Mabilleau G, Pereira M, Chenu C. Novel skeletal effects of glucagon-like peptide-1 (GLP-1) receptor agonists. J Endocrinol. 2018; 236: R29–R42.
Zhao C, Liang J, Yang Y, et al. The impact of glucagon-like peptide-1 on bone metabolism and its possible mechanisms. Front Endocrinol. 2017; 8: 98.
Daniiloupolou I, Vlachou E, Lambrou GI, et al. The impact of GLP-1 agonists on bone metabolism: a systematic review. Medicina 2022; 58: 224.
Tilinca MC, Tiuca RA, Niculas C, et al. Future perspectives in diabesity treatment: semaglutide, a glucagon-like peptide-1 receptor agonist (review). Exp Ther Med. 2021; 22: 1167.
Del Prato S, Kang J, Trautmann ME, et al. Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: results of a phase 2 placebo-controlled, 16-week randomized dose-finding study. Diabetes Obes Metab. 2020; 22: 1176–1186.
Pratley RE, Jacob S, Baek S, et al. Efficacy and safety of efpeglenatide in key patient subgroups from the BALANCE randomized trial, stratified by pre-diabetes status, BMI and age at baseline. BMJ Open Diabetes Res Care 2022; 10: e002207.
Kawai T, Sun B, Yoshino H, et al. Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist. Proc Natl Acad Sci U S A 2020; 117: 29959–29967.
Hasib A. Multiagonist unimolecular peptides for obesity and type 2 diabetes: current advances and future directions. Clin Med Insights Endocrinol Diabetes 2020; 13: 1179551420905844.
Evers A, Bossart M, Pfeiffer-Marek S, et al. Dual glucagon-like peptide 1 (GLP-1)/glucagon receptor agonists specifically optimized for multidose formulations. J Med Chem. 2018; 61: 5580–5593.
Bajaj HS, Bergenstal RM, Christoffersen A, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in type 2 diabetes inadequately controlled on daily basal insulin: a phase 2 randomized controlled trial. Diabetes Care 2021, 44: 1586–1594.