Incretin-based therapies for type 2 diabetes mellitus

被引:536
作者
Lovshin, Julie A. [1 ]
Drucker, Daniel J. [1 ]
机构
[1] Univ Toronto, Mt Sinai Hosp, Dept Med, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3L9, Canada
关键词
GLUCAGON-LIKE PEPTIDE-1; DIPEPTIDYL PEPTIDASE-4 INHIBITOR; ONGOING METFORMIN THERAPY; GLYCEMIC CONTROL; DOUBLE-BLIND; EXENATIDE EXENDIN-4; RANDOMIZED-TRIAL; GLUCOSE-HOMEOSTASIS; TREATED PATIENTS; NON-INFERIORITY;
D O I
10.1038/nrendo.2009.48
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Incretin-based drugs, such as glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, are now routinely used to treat type 2 diabetes mellitus. These agents regulate glucose metabolism through multiple mechanisms, their use is associated with low rates of hypoglycemia, and they either do not affect body weight (dipeptidyl peptidase 4 inhibitors), or promote weight loss (glucagon-like peptide-1 receptor agonists). The success of exenatide and sitagliptin, the first therapies in their respective drug classes to be based on incretins, has fostered the development of multiple new agents that are currently in late stages of clinical development or awaiting approval. This review highlights our current understanding of the mechanisms of action of incretin-based drugs, with an emphasis on the emerging clinical profile of new agents.
引用
收藏
页码:262 / 269
页数:8
相关论文
共 56 条
[31]   Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea [J].
Kendall, DM ;
Riddle, MC ;
Rosenstock, J ;
Zhuang, DL ;
Kim, DD ;
Fineman, MS ;
Baron, AD .
DIABETES CARE, 2005, 28 (05) :1083-1091
[32]   DEGRADATION OF GLUCOSE-DEPENDENT INSULINOTROPIC POLYPEPTIDE AND TRUNCATED GLUCAGON-LIKE PEPTIDE-1 IN-VITRO AND IN-VIVO BY DIPEPTIDYL PEPTIDASE-IV [J].
KIEFFER, TJ ;
MCINTOSH, CHS ;
PEDERSON, RA .
ENDOCRINOLOGY, 1995, 136 (08) :3585-3596
[33]   Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes [J].
Kim, Dennis ;
MacConell, Leigh ;
Zhuang, Dongliang ;
Kothare, Prajakti A. ;
Trautmann, Michael ;
Fineman, Mark ;
Taylor, Kristin .
DIABETES CARE, 2007, 30 (06) :1487-1493
[34]  
KREYMANN B, 1987, LANCET, V2, P1300
[35]   Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes - Potential importance of selectivity over dipeptidyl peptidases 8 and 9 [J].
Lankas, GR ;
Leiting, B ;
Roy, RS ;
Eiermann, GJ ;
Beconi, MG ;
Biftu, T ;
Chan, CC ;
Edmondson, S ;
Feeney, WP ;
He, HB ;
Ippolito, DE ;
Kim, D ;
Lyons, KA ;
Ok, HO ;
Patel, RA ;
Petrov, AN ;
Pryor, KA ;
Qian, XX ;
Reigle, L ;
Woods, A ;
Wu, JK ;
Zaller, D ;
Zhang, XP ;
Zhu, L ;
Weber, AE ;
Thornberry, NA .
DIABETES, 2005, 54 (10) :2988-2994
[36]  
MARRE M, 2009, DIABETIC MED 0114, DOI DOI 10.1111/J.1464-54912009.02666.X
[37]   Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Albiglutide, a Long-Acting Glucagon-Like Peptide-1 Mimetic, in Patients with Type 2 Diabetes [J].
Matthews, Jessica E. ;
Stewart, Murray W. ;
De Boever, Erika H. ;
Dobbins, Robert L. ;
Hodge, Rebecca J. ;
Walker, Susan E. ;
Holland, M. Claire ;
Bush, Mark A. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (12) :4810-4817
[38]   A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study [J].
Nauck, M. A. ;
Duran, S. ;
Kim, D. ;
Johns, D. ;
Northrup, J. ;
Festa, A. ;
Brodows, R. ;
Trautmann, M. .
DIABETOLOGIA, 2007, 50 (02) :259-267
[39]   Efficacy and safety of adding the dipeptidyl peptidase-4 inhibitor alogliptin to metformin therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a multicentre, randomised, double-blind, placebo-controlled study [J].
Nauck, M. A. ;
Ellis, G. C. ;
Fleck, P. R. ;
Wilson, C. A. ;
Mekki, Q. .
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, 2009, 63 (01) :46-55
[40]   PRESERVED INCRETIN ACTIVITY OF GLUCAGON-LIKE PEPTIDE-1 [7-36 AMIDE] BUT NOT OF SYNTHETIC HUMAN GASTRIC-INHIBITORY POLYPEPTIDE IN PATIENTS WITH TYPE-2 DIABETES-MELLITUS [J].
NAUCK, MA ;
HEIMESAAT, MM ;
ORSKOV, C ;
HOLST, JJ ;
EBERT, R ;
CREUTZFELDT, W .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 91 (01) :301-307