The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems

被引：123

作者：

Seufert, J. ^{[1
]}

Gallwitz, B. ^{[2
]}

机构：

[1] Univ Freiburg, Med Ctr, Div Endocrinol & Diabetol, Dept Med 2, Freiburg, Germany

[2] Univ Tubingen, Dept Med 4, Tubingen, Germany

来源：

DIABETES OBESITY & METABOLISM | 2014年 / 16卷 / 08期

关键词：

GLP-1; receptor agonists; liraglutide; exenatide; lixisenatide; cardiovascular; gastrointestinal; central nervous system; GLUCAGON-LIKE PEPTIDE-1; ACUTE MYOCARDIAL-INFARCTION; METFORMIN-TREATED PATIENTS; TYPE-2; DIABETES-MELLITUS; GLYCEMIC CONTROL; DOUBLE-BLIND; OPEN-LABEL; EXENATIDE EXENDIN-4; ANALOG LIRAGLUTIDE; RISK-FACTORS;

D O I：

10.1111/dom.12251

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The glucagon-like peptide-1 receptor agonists (GLP-1RAs) exenatide, liraglutide and lixisenatide have been shown to improve glycaemic control and beta-cell function with a low risk of hypoglycaemia in people with type 2 diabetes. GLP-1 receptors are also expressed in extra-pancreatic tissues and trial data suggest that GLP-1RAs also have effects beyond their glycaemic actions. Preclinical studies using native GLP-1 or GLP-1RAs provide substantial evidence for cardioprotective effects, while clinical trial data have shown beneficial actions on hypertension and dyslipidaemia in people with type 2 diabetes. Significant weight loss has been reported with GLP-1RAs in both people with type 2 diabetes and obese people without diabetes. GLP-1RAs also slow down gastric emptying, but preclinical data suggest that the main mechanism behind GLP-1RA-induced weight loss is more likely to involve their effects on appetite signalling in the brain. GLP-1RAs have also been shown to exert a neuroprotective role in rodent models of stroke, Alzheimer's disease and Parkinson's disease. These extra-pancreatic effects of GLP-1RAs could provide multi-factorial benefits to people with type 2 diabetes. Potential adverse effects of GLP-1RA treatment are usually manageable but may include gastrointestinal effects, increased heart rate and renal injury. While extensive further research is still required, early data suggest that GLP-1RAs may also have the potential to favourably impact cardiovascular disease, obesity or neurological disorders in people without diabetes in the future.

引用

页码：673 / 688

页数：16

共 152 条

[11] Effect of additional treatment with EXenatide in patients with an Acute Myocardial Infarction: The EXAMI study [J].

Bernink, Flip J. P. ;

Timmers, Leo ;

Diamant, Michaela ;

Scholte, Martijn ;

Beek, Aernout M. ;

Kamp, Otto ;

Marques, Koen M. J. ;

Denham, Robert N. ;

Chen, Weena J. Y. ;

Doevendans, Pieter A. ;

van Rossum, Albert C. ;

van Royen, Niels ;

Horrevoets, Anton J. G. ;

Appelman, Yolande .

INTERNATIONAL JOURNAL OF CARDIOLOGY, 2013, 167 (01) :289-290

[12] Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels - A meta-analysis of 21 cohort studies including more than 300,000 persons [J].

Bogers, Rik P. ;

Bemelmans, Wanda J. E. ;

Hoogenveen, Rudolf T. ;

Boshuizen, Hendriek C. ;

Woodward, Mark ;

Knekt, Paul ;

van Dam, Rob M. ;

Hu, Frank B. ;

Visscher, Tommy L. S. ;

Menotti, Alessandro ;

Thorpe, Roland J., Jr. ;

Jamrozik, Konrad ;

Calling, Susanna ;

Strand, Bjorn Heine ;

Shipley, Martin J. .

ARCHIVES OF INTERNAL MEDICINE, 2007, 167 (16) :1720-1728

[13] Association of Exenatide With Liver Enzymes in Patients With Type 2 Diabetes [J].

Bulchandani, Deepti ;

Nachnani, Jagdish S. ;

Eaton, Crystal ;

Hamburg, Mitchell .

ENDOCRINOLOGIST, 2009, 19 (03) :114-115

[14] Effects of Exenatide on Measures of β-Cell Function After 3 Years in Metformin-Treated Patients With Type 2 Diabetes [J].

Bunck, Mathijs C. ;

Corner, Anja ;

Ellasson, Bjorn ;

Heine, Robert J. ;

Shaginian, Rimma M. ;

Taskinen, Marja-Riitta ;

Smith, Ulf ;

Yki-Jarvinen, Hannele ;

Diamant, Michaela .

DIABETES CARE, 2011, 34 (09) :2041-2047

[15] Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes [J].

Buse, JB ;

Henry, RR ;

Han, J ;

Kim, DD ;

Fineman, MS ;

Baron, AD .

DIABETES CARE, 2004, 27 (11) :2628-2635

[16] Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study [J].

Buse, John B. ;

Nauck, Michael ;

Forst, Thomas ;

Sheu, Wayne H-H ;

Shenouda, Sylvia K. ;

Heilmann, Cory R. ;

Hoogwerf, Byron J. ;

Gao, Aijun ;

Boardman, Marilyn K. ;

Fineman, Mark ;

Porter, Lisa ;

Schernthaner, Guntram .

LANCET, 2013, 381 (9861) :117-124

[17] 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].

Buse, John B. ;

Rosenstock, Julio ;

Sesti, Giorgio ;

Schmidt, Wolfgang E. ;

Montanya, Eduard ;

Brett, Jason H. ;

Zychma, Marcin ;

Blonde, Lawrence .

LANCET, 2009, 374 (9683) :39-47

[18] Marked Expansion of Exocrine and Endocrine Pancreas With Incretin Therapy in Humans With Increased Exocrine Pancreas Dysplasia and the Potential for Glucagon-Producing Neuroendocrine Tumors [J].

Butler, Alexandra E. ;

Campbell-Thompson, Martha ;

Gurlo, Tatyana ;

Dawson, David W. ;

Atkinson, Mark ;

Butler, Peter C. .

DIABETES, 2013, 62 (07) :2595-2604

[19] Improvement of psoriasis during exenatide treatment in a patient with diabetes [J].

Buysschaert, M. ;

Tennstedt, D. ;

Preumont, V. .

DIABETES & METABOLISM, 2012, 38 (01) :86-88

[20] Absence of QTc Prolongation in a Thorough QT Study With Subcutaneous Liraglutide, a Once-Daily Human GLP-1 Analog for Treatment of Type 2 Diabetes [J].

Chatterjee, Dhruba J. ;

Khutoryansky, Naum ;

Zdravkovic, Milan ;

Sprenger, Craig R. ;

Litwin, Jeffrey S. .

JOURNAL OF CLINICAL PHARMACOLOGY, 2009, 49 (11) :1353-1362

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