Impact of Liraglutide 3.0 on Body Fat Distribution

Summary

This study is a clinical study to investigate the efficacy of liraglutide compared to placebo in reducing visceral adiposity measured by MRI in overweight or obese subjects at high risk for cardiovascular disease after 40 weeks on-treatment.

Timeline

Start

2017-01

Primary completion

2020-10-13

Completion

2020-10-13

Outcome

Met primary endpoint

paper once-daily liraglutide 3·0 mg plus lifestyle intervention significantly lowered visceral adipose tissue over 40 weeks of treatment. PMID 34358471 ↗

paper Mean change in VAT over median 36·2 weeks was -12·49% (SD 9·3%) with liraglutide compared with -1·63% (SD 12·3%) with placebo PMID 34358471 ↗

Publications

• Background Astrup A, Rossner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME; NN8022-1807 Study Group. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet. 2009 Nov 7;374(9701):1606-16. doi: 10.1016/S0140-6736(09)61375-1. Epub 2009 Oct 23.
• Background Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rossner S, Savolainen MJ, Van Gaal L; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158. Epub 2011 Aug 16.
• Background Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Fernando Costa. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: Executive Summary. Crit Pathw Cardiol. 2005 Dec;4(4):198-203. doi: 10.1097/00132577-200512000-00018. No abstract available.
• Background Berrington de Gonzalez A, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Freeman LB, Beeson WL, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010 Dec 2;363(23):2211-9. doi: 10.1056/NEJMoa1000367.
• Background Despres JP. Body fat distribution and risk of cardiovascular disease: an update. Circulation. 2012 Sep 4;126(10):1301-13. doi: 10.1161/CIRCULATIONAHA.111.067264. No abstract available.
• Background Garvey WT, Garber AJ, Mechanick JI, Bray GA, Dagogo-Jack S, Einhorn D, Grunberger G, Handelsman Y, Hennekens CH, Hurley DL, McGill J, Palumbo P, Umpierrez G; The Aace Obesity Scientific Committee. American association of clinical endocrinologists and american college of endocrinology position statement on the 2014 advanced framework for a new diagnosis of obesity as a chronic disease. Endocr Pract. 2014 Sep;20(9):977-89. doi: 10.4158/EP14280.PS. No abstract available.
• Background Morkedal B, Vatten LJ, Romundstad PR, Laugsand LE, Janszky I. Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (Nord-Trondelag Health Study), Norway. J Am Coll Cardiol. 2014 Mar 25;63(11):1071-8. doi: 10.1016/j.jacc.2013.11.035. Epub 2013 Dec 15.
• Background Despres JP, Lemieux I, Bergeron J, Pibarot P, Mathieu P, Larose E, Rodes-Cabau J, Bertrand OF, Poirier P. Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol. 2008 Jun;28(6):1039-49. doi: 10.1161/ATVBAHA.107.159228. Epub 2008 Mar 20.
• Background McLaughlin T, Lamendola C, Liu A, Abbasi F. Preferential fat deposition in subcutaneous versus visceral depots is associated with insulin sensitivity. J Clin Endocrinol Metab. 2011 Nov;96(11):E1756-60. doi: 10.1210/jc.2011-0615. Epub 2011 Aug 24.
• Background McLaughlin T, Sherman A, Tsao P, Gonzalez O, Yee G, Lamendola C, Reaven GM, Cushman SW. Enhanced proportion of small adipose cells in insulin-resistant vs insulin-sensitive obese individuals implicates impaired adipogenesis. Diabetologia. 2007 Aug;50(8):1707-15. doi: 10.1007/s00125-007-0708-y. Epub 2007 Jun 5.
• Background See R, Abdullah SM, McGuire DK, Khera A, Patel MJ, Lindsey JB, Grundy SM, de Lemos JA. The association of differing measures of overweight and obesity with prevalent atherosclerosis: the Dallas Heart Study. J Am Coll Cardiol. 2007 Aug 21;50(8):752-9. doi: 10.1016/j.jacc.2007.04.066. Epub 2007 Aug 6.
• Background Cerhan JR, Moore SC, Jacobs EJ, Kitahara CM, Rosenberg PS, Adami HO, Ebbert JO, English DR, Gapstur SM, Giles GG, Horn-Ross PL, Park Y, Patel AV, Robien K, Weiderpass E, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hartge P, Bernstein L, Berrington de Gonzalez A. A pooled analysis of waist circumference and mortality in 650,000 adults. Mayo Clin Proc. 2014 Mar;89(3):335-45. doi: 10.1016/j.mayocp.2013.11.011.
• Background Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.
• Background Hsu WC, Araneta MR, Kanaya AM, Chiang JL, Fujimoto W. BMI cut points to identify at-risk Asian Americans for type 2 diabetes screening. Diabetes Care. 2015 Jan;38(1):150-8. doi: 10.2337/dc14-2391. No abstract available.
• Background Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA. Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity (Silver Spring). 2013 Sep;21(9):E439-47. doi: 10.1002/oby.20135. Epub 2013 May 19.
• Background Neeland IJ, Turer AT, Ayers CR, Powell-Wiley TM, Vega GL, Farzaneh-Far R, Grundy SM, Khera A, McGuire DK, de Lemos JA. Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults. JAMA. 2012 Sep 19;308(11):1150-9. doi: 10.1001/2012.jama.11132.
• Background Chandra A, Neeland IJ, Berry JD, Ayers CR, Rohatgi A, Das SR, Khera A, McGuire DK, de Lemos JA, Turer AT. The relationship of body mass and fat distribution with incident hypertension: observations from the Dallas Heart Study. J Am Coll Cardiol. 2014 Sep 9;64(10):997-1002. doi: 10.1016/j.jacc.2014.05.057.
• Background Neeland IJ, Gupta S, Ayers CR, Turer AT, Rame JE, Das SR, Berry JD, Khera A, McGuire DK, Vega GL, Grundy SM, de Lemos JA, Drazner MH. Relation of regional fat distribution to left ventricular structure and function. Circ Cardiovasc Imaging. 2013 Sep;6(5):800-7. doi: 10.1161/CIRCIMAGING.113.000532. Epub 2013 Aug 8.
• Background Britton KA, Massaro JM, Murabito JM, Kreger BE, Hoffmann U, Fox CS. Body fat distribution, incident cardiovascular disease, cancer, and all-cause mortality. J Am Coll Cardiol. 2013 Sep 3;62(10):921-5. doi: 10.1016/j.jacc.2013.06.027. Epub 2013 Jul 10.
• Background Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, Aronne L; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes (Lond). 2013 Nov;37(11):1443-51. doi: 10.1038/ijo.2013.120. Epub 2013 Jul 1.
• Background Borga M, Thomas EL, Romu T, Rosander J, Fitzpatrick J, Dahlqvist Leinhard O, Bell JD. Validation of a fast method for quantification of intra-abdominal and subcutaneous adipose tissue for large-scale human studies. NMR Biomed. 2015 Dec;28(12):1747-53. doi: 10.1002/nbm.3432. Epub 2015 Nov 2.
• Background Schaudinn A, Linder N, Garnov N, Kerlikowsky F, Bluher M, Dietrich A, Schutz T, Karlas T, Kahn T, Busse H. Predictive accuracy of single- and multi-slice MRI for the estimation of total visceral adipose tissue in overweight to severely obese patients. NMR Biomed. 2015 May;28(5):583-90. doi: 10.1002/nbm.3286. Epub 2015 Mar 25.
• Background Dong Z, Luo Y, Zhang Z, Cai H, Li Y, Chan T, Wu L, Li ZP, Feng ST. MR quantification of total liver fat in patients with impaired glucose tolerance and healthy subjects. PLoS One. 2014 Oct 24;9(10):e111283. doi: 10.1371/journal.pone.0111283. eCollection 2014.
• Background Thomas MS, Newman D, Leinhard OD, Kasmai B, Greenwood R, Malcolm PN, Karlsson A, Rosander J, Borga M, Toms AP. Test-retest reliability of automated whole body and compartmental muscle volume measurements on a wide bore 3T MR system. Eur Radiol. 2014 Sep;24(9):2279-91. doi: 10.1007/s00330-014-3226-6. Epub 2014 May 29.
• Background Human energy requirements: report of a joint FAO/ WHO/UNU Expert Consultation. Food Nutr Bull. 2005 Mar;26(1):166. No abstract available.
• Neeland IJ, Marso SP, Ayers CR, Lewis B, Oslica R, Francis W, Rodder S, Pandey A, Joshi PH. Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Diabetes Endocrinol. 2021 Sep;9(9):595-605. doi: 10.1016/S2213-8587(21)00179-0. Epub 2021 Aug 3.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Liraglutide	Peptide	3 mg	Subcutaneous

Indications