The "other" incretin - the therapeutic rediscovery of the glucose-dependent insulinotropic polypeptide

被引:2
作者
Winkler, Gabor [1 ,2 ,3 ]
Kis, Janos Tibor [1 ]
Schandl, Laszlo [1 ]
机构
[1] Eszak Kozep Buda Ctr, EKC Uj Szent Janos Korhaz Szakrendelo, Belgyogyaszat Diabetol 2, Budapest, Hungary
[2] Miskolc Egyet, Elmelet Egeszsegtud Int, Egeszsegtud Kar, Miskolc, Hungary
[3] Dios Arok 1-3, H-1125 Budapest, Hungary
关键词
glucose-dependent insulinotrope polypeptide; glucagon-like peptide-1; dual receptor agonism; tirzepa-tide; SURPASS and SURMOUNT trials; GLP-1 RECEPTOR AGONIST; DUAL GIP; TIRZEPATIDE; DISCOVERY; GUT;
D O I
10.1556/650.2023.32710
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Among the two incretins that strongly stimulate insulin secretion and are also involved in its physiological regulation in type 2 diabetes, glucagon-like peptide-1 (GLP1) has been the focus of interest for a long time, due to its retained - although reduced - secretagogue nature also in type 2 diabetes. Its receptor agonists were also included in the antidiabetic treatment toolkit. In the light of more recent studies, however, the "other" incretin, the glucose -de-pendent insulinotropic polypeptide (GIP) has also come into a different light. It turned out that by regulating gluca-gon and insulin production according to blood sugar levels, it acts as a bifunctional blood sugar stabilizing factor in type 2 diabetes as well. The article reviews new data on the physiology of GIP, its verifiable effects in type 2 diabetes and obesity, the so-called "twincretin" effect as well as the benefits of the double stimulation of the GIP and the GLP1 receptor. It describes the pharmacology of the first dual receptor agonist, tirzepatide, already incorporated in therapeutic recommendations, and the first clinical trials related to its use. In the light of the data so far, the molecule may open new horizons in the treatment of type 2 diabetes and obesity.
引用
收藏
页码:210 / 218
页数:9
相关论文
共 41 条
[1]  
Christensen MB, 2016, DAN MED J, V63
[2]   LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept [J].
Coskun, Tamer ;
Sloop, Kyle W. ;
Loghin, Corina ;
Alsina-Fernandez, Jorge ;
Urva, Shweta ;
Bokvist, Krister B. ;
Cui, Xuewei ;
Briere, Daniel A. ;
Cabrera, Over ;
Roell, William C. ;
Kuchibhotla, Uma ;
Moyers, Julie S. ;
Benson, Charles T. ;
Gimeno, Ruth E. ;
D'Alessio, David A. ;
Haupt, Axel .
MOLECULAR METABOLISM, 2018, 18 :3-14
[3]   Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes The SURPASS-5 Randomized Clinical Trial [J].
Dahl, Dominik ;
Onishi, Yukiko ;
Norwood, Paul ;
Huh, Ruth ;
Bray, Ross ;
Patel, Hiren ;
Rodriguez, Angel .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2022, 327 (06) :534-545
[4]   Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) [J].
Davies, Melanie J. ;
Aroda, Vanita R. ;
Collins, Billy S. ;
Gabbay, Robert A. ;
Green, Jennifer ;
Maruthur, Nisa M. ;
Rosas, Sylvia E. ;
Del Prato, Stefano ;
Mathieu, Chantal ;
Mingrone, Geltrude ;
Rossing, Peter ;
Tankova, Tsvetalina ;
Tsapas, Apostolos ;
Buse, John B. .
DIABETES CARE, 2022, 45 (11) :2753-2786
[5]   Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial [J].
Del Prato, Stefano ;
Kahn, Steven E. ;
Pavo, Imre ;
Weerakkody, Govinda J. ;
Yang, Zhengyu ;
Doupis, John ;
Aizenberg, Diego ;
Wynne, Alan G. ;
Riesmeyer, Jeffrey S. ;
Heine, Robert J. ;
Wiese, Russell J. .
LANCET, 2021, 398 (10313) :1811-1824
[6]   The role of GIP in α-cells and glucagon secretion [J].
El, Kimberley ;
Campbell, Jonathan E. .
PEPTIDES, 2020, 125
[7]   Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes [J].
Frias, Juan P. ;
Davies, Melanie J. ;
Rosenstock, Julio ;
Manghi, Federico C. Perez ;
Lando, Laura Fernandez ;
Bergman, Brandon K. ;
Liu, Bing ;
Cui, Xuewei ;
Brown, Katelyn .
NEW ENGLAND JOURNAL OF MEDICINE, 2021, 385 (06) :503-515
[8]   The Role of GIP Receptor in the CNS for the Pathogenesis of Obesity [J].
Fukuda, Makoto .
DIABETES, 2021, 70 (09) :1929-1937
[9]   Clinical perspectives on the use of the GIP/GLP-1 receptor agonist tirzepatide for the treatment of type-2 diabetes and obesity [J].
Gallwitz, Baptist .
FRONTIERS IN ENDOCRINOLOGY, 2022, 13
[10]  
Gupta K, 2022, STATPEARLS