GLP-1受体激动剂/类似物治疗2型糖尿病的研究进展
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摘要
胰高血糖素样肽-1(GLP-1)是一种由肠道L细胞分泌,在碳水化合物的刺激下促进胰岛素的分泌进而降低血糖的一种物质。胰高血糖素样肽-1受体激动剂(GLP-1RA)是通过刺激人体内源性GLP-1的生成而产生降糖作用,因其良好的降糖效果及其对于大、小血管的保护作用而广受临床医生及科研专家的关注。本文通过检索文献对其心血管获益、减重方面进行综述,并对目前已在我国上市并在临床上取得良好应用的几种GLP-1RA进行简要介绍。
Glucagon-like peptide-1 is a substance which is secreted by intestinal L cell and stimulated by carbohydrates to secrete enough insulin to reduce blood glucose.Glucagon-like peptide 1 receptor agonist(GLP-1RAs)has a hypoglycemic effect by stimulating the production of endogenous GLP-1 in human body.It is widely concerned by clinicians and scientific research experts because of its good hypoglycemic effect and its protective effect on vessels.Through literature search,this paper firstly reviews the cardiovascular benefits,weight loss and other aspects,and briefly introduces several GLP-1 RAs which have been listed in China and have been applied in clinical practice.
Glucagon-like peptide-1 is a substance which is secreted by intestinal L cell and stimulated by carbohydrates to secrete enough insulin to reduce blood glucose.Glucagon-like peptide 1 receptor agonist(GLP-1RAs)has a hypoglycemic effect by stimulating the production of endogenous GLP-1 in human body.It is widely concerned by clinicians and scientific research experts because of its good hypoglycemic effect and its protective effect on vessels.Through literature search,this paper firstly reviews the cardiovascular benefits,weight loss and other aspects,and briefly introduces several GLP-1 RAs which have been listed in China and have been applied in clinical practice.
引文
[1] Inzucchi SE,Bergenstal RM,Buse JB,et al.Management of hyperglycemia in type 2 diabetes:a patient-centeredapproach:position statement of the American Diabetes Association(ADA) and the European Association for the study of diabetes (EASD)[J].Diabetes Care,2012,35(6):1364-1379.
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[3] Vitale C,Mercuro G,Cornoldi A,et al.Metformin improves endothelial function in patients with metabolic syndrome[J].J Intern Med,2005,258(3):250-256.
[4] Sun W,Zeng C,Liao L,et al.Comparison of acarbose and metformin therapy in newly diagnosed type 2 diabetic patients with overweight and/or obese[J].Curr Med Res Opin,2016,32:1389-1396.
[5] Holst JJ.Glucagonlike peptide 1:a newly discovered gastrointestinal hormone[J].Gastroenterology,1994,107(6):1848-1855.
[6] Meier JJ.GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus[J].Nat Rev Endocrinol,2012,8(12):728-742.
[7] Vilsb T,Christensen M,Junker AE,et al.Effects of glucagon-like peptide-1 receptor agonists on weight loss:systematic review and meta-analyses of randomised controlled trials[J].BMJ,2012,344:d7771.
[8] Madsbad S,Schmitz O,Ranstam J,et al,NN2211-1310 International Study Group.Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211):a 12-week,double-blind,randomized,controlled trial[J].Diabetes Care,2004,27(6):1335-1342.
[9] 周黎,方煜,胡明,等.GLP-1类似物及DPP-4抑制剂国内上市情况分析[J].中国药业,2019,28(3):96
[10] Zinman B,Gerich J,Buse JB,et al.Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD) [J].Diabetes Care,2009,32(7):1224-1230.
[11] Marre M,Shaw J,Brdle M,et al.Liraglutide,a once-daily human GLP-1 analogue,added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU) [J].Diabet Med,2009,26(3):268-278.
[12] Garber A,Henry R,Ratner R,et al.Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono):a randomised,52-week,phase III,double-blind,parallel-treatment trial[J].Lancet,2009,373(9662):473-481.
[13] Buse JB,Rosenstock J,Sesti G,et al.Liraglutide once a day versus exenatide twice a day for type 2 diabetes:a 26-week randomised,parallel-group,multinational,open-label trial (LEAD- 6) [J].Lancet,2009,374(9683):39-47.
[14] Christian Anholm,Preman Kumarathurai,Anders Jürs,et al,Liraglutide improves the bata-cell function without increasing insulin secretion during a mixed meal in patients,who exhibit well-controlled type 2 diabetes and coronary artery disease[J].Diabetol Metab Syndr,2019,11:42
[15] Zhang Y,Liu S,Fan C,et al.Effect of glucagon-like peptide 1 receptor agonist on body fat redistribution and muscle mass in overweight and obese type 2diabetic patients[J].Nan Fang Yi Ke Da Xue Xue Bao,2019,10:1673-4254.
[16] Moreno C,Mistry M,Roman RJ.Renal effects of glucagon-like peptide in rats [J].Eur J Pharmacol,2002,434(3):163-167.
[17] Nolen-Doeer E,Stockman MC,Rizo I.Mechanism of glucagon-like peptide 1 improvements in type 2 diabetes mellitus and obesity[J].Curr Obes Rep,2019.
[18] Gaspari T,Liu H,Welungoda I,et al.A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model[J].Diab Vasc Dis Res,2011,8(2):117-124.
[19] Rso SP,Daniels GH,Brown-Frandsen K,et al.Liraglutide and cardiovascular outcomes in type 2 diabetes[J].N Engl J Med,2016,375(4):311-322.
[20] Marso SP,Bain SC,Consoli A,et al.Semaglutide and cardiovascular outcomes in patients with type 2 diabetes[J].N Engl J Med,2016,375(19):1834-1844.
[21] Uscogiuri G,Cignarelli A,Giorgino F,et al.GLP-1:benefits beyond pancreas[J].J Endoceinol Invest,2014,37(12):1143-1153.
[22] Reutens AT.Epidermiology of diabetic kidney disease[J].Med Clin North Arn,2013,97:1-18.
[23] Manie J,Davies,Stephen CB,et al.Efficacy and safety of liragluglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL):a randomized clinical trial[J].Diab Care,2016,39:222-230
[24] Parlevliet ET,Schroder-van der Elst JP,Corssmit EP,et al.CNTO736,anovel glucagon-like peptide-1 recepter agonist,ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice[J].J Pharacol Exp Ther,2009,328(1):240-248.
[2] Maruthur NM,Tseng E,Hutfless S,et al.Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes:a systematic review and meta-analysis[J].Ann Intern Med,2016,164:740-751.
[3] Vitale C,Mercuro G,Cornoldi A,et al.Metformin improves endothelial function in patients with metabolic syndrome[J].J Intern Med,2005,258(3):250-256.
[4] Sun W,Zeng C,Liao L,et al.Comparison of acarbose and metformin therapy in newly diagnosed type 2 diabetic patients with overweight and/or obese[J].Curr Med Res Opin,2016,32:1389-1396.
[5] Holst JJ.Glucagonlike peptide 1:a newly discovered gastrointestinal hormone[J].Gastroenterology,1994,107(6):1848-1855.
[6] Meier JJ.GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus[J].Nat Rev Endocrinol,2012,8(12):728-742.
[7] Vilsb T,Christensen M,Junker AE,et al.Effects of glucagon-like peptide-1 receptor agonists on weight loss:systematic review and meta-analyses of randomised controlled trials[J].BMJ,2012,344:d7771.
[8] Madsbad S,Schmitz O,Ranstam J,et al,NN2211-1310 International Study Group.Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide 1 analog liraglutide (NN2211):a 12-week,double-blind,randomized,controlled trial[J].Diabetes Care,2004,27(6):1335-1342.
[9] 周黎,方煜,胡明,等.GLP-1类似物及DPP-4抑制剂国内上市情况分析[J].中国药业,2019,28(3):96
[10] Zinman B,Gerich J,Buse JB,et al.Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met + TZD) [J].Diabetes Care,2009,32(7):1224-1230.
[11] Marre M,Shaw J,Brdle M,et al.Liraglutide,a once-daily human GLP-1 analogue,added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU) [J].Diabet Med,2009,26(3):268-278.
[12] Garber A,Henry R,Ratner R,et al.Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono):a randomised,52-week,phase III,double-blind,parallel-treatment trial[J].Lancet,2009,373(9662):473-481.
[13] Buse JB,Rosenstock J,Sesti G,et al.Liraglutide once a day versus exenatide twice a day for type 2 diabetes:a 26-week randomised,parallel-group,multinational,open-label trial (LEAD- 6) [J].Lancet,2009,374(9683):39-47.
[14] Christian Anholm,Preman Kumarathurai,Anders Jürs,et al,Liraglutide improves the bata-cell function without increasing insulin secretion during a mixed meal in patients,who exhibit well-controlled type 2 diabetes and coronary artery disease[J].Diabetol Metab Syndr,2019,11:42
[15] Zhang Y,Liu S,Fan C,et al.Effect of glucagon-like peptide 1 receptor agonist on body fat redistribution and muscle mass in overweight and obese type 2diabetic patients[J].Nan Fang Yi Ke Da Xue Xue Bao,2019,10:1673-4254.
[16] Moreno C,Mistry M,Roman RJ.Renal effects of glucagon-like peptide in rats [J].Eur J Pharmacol,2002,434(3):163-167.
[17] Nolen-Doeer E,Stockman MC,Rizo I.Mechanism of glucagon-like peptide 1 improvements in type 2 diabetes mellitus and obesity[J].Curr Obes Rep,2019.
[18] Gaspari T,Liu H,Welungoda I,et al.A GLP-1 receptor agonist liraglutide inhibits endothelial cell dysfunction and vascular adhesion molecule expression in an ApoE-/- mouse model[J].Diab Vasc Dis Res,2011,8(2):117-124.
[19] Rso SP,Daniels GH,Brown-Frandsen K,et al.Liraglutide and cardiovascular outcomes in type 2 diabetes[J].N Engl J Med,2016,375(4):311-322.
[20] Marso SP,Bain SC,Consoli A,et al.Semaglutide and cardiovascular outcomes in patients with type 2 diabetes[J].N Engl J Med,2016,375(19):1834-1844.
[21] Uscogiuri G,Cignarelli A,Giorgino F,et al.GLP-1:benefits beyond pancreas[J].J Endoceinol Invest,2014,37(12):1143-1153.
[22] Reutens AT.Epidermiology of diabetic kidney disease[J].Med Clin North Arn,2013,97:1-18.
[23] Manie J,Davies,Stephen CB,et al.Efficacy and safety of liragluglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL):a randomized clinical trial[J].Diab Care,2016,39:222-230
[24] Parlevliet ET,Schroder-van der Elst JP,Corssmit EP,et al.CNTO736,anovel glucagon-like peptide-1 recepter agonist,ameliorates insulin resistance and inhibits very low-density lipoprotein production in high-fat-fed mice[J].J Pharacol Exp Ther,2009,328(1):240-248.