Effects of exenatide versus insulin glargine on body composition in overweight and obese T2DM patients: a randomized controlled trial

Ting-Ting Yin, Yan Bi, Ping Li, Shan-Mei Shen, Wei-Min Wang, Can Jiang, Cai-Xia Gao, Yan Wang, Li-Jun Gao, Da-Long Zhu, Wen-Huan Feng, Ting-Ting Yin, Yan Bi, Ping Li, Shan-Mei Shen, Wei-Min Wang, Can Jiang, Cai-Xia Gao, Yan Wang, Li-Jun Gao, Da-Long Zhu, Wen-Huan Feng

Abstract

Background: Weight loss, especially fat mass reduction, helps to improve blood glucose control, insulin sensitivity, and β-cell function. This study aimed to compare the effect of exenatide and glargine on body composition in overweight and obese patients with type 2 diabetes (T2DM) who do not achieve adequate glycemic control with metformin.

Methods: We performed a prospective, randomized study of 37 overweight or obese patients with T2DM who had inadequate glycemic control with metformin. The patients were treated with either exenatide or glargine for 16 weeks. Dual-energy X-ray absorptiometry was used to assess body composition.

Results: Post-intervention weight, body mass index (BMI), waist circumference, body mass, and fat mass were lower in patients treated with exenatide, while weight and BMI significantly increased with glargine. Reductions in weight, BMI, body fat mass, and percent fat mass (except for gynoid) were greater with exenatide than with glargine, and percent lean tissue (other than the limbs) increased with exenatide. In all body regions except for the limbs, fat mass decreased with exenatide to a greater extent than lean tissue. Glucose control, insulin resistance, and β-cell function were not different between the treatment groups.

Conclusions: For overweight and obese patients whose T2DM was inadequately controlled with metformin, exenatide and glargine achieved similar improvements in glycemic control, insulin sensitivity, and β-cell function.However, exenatide produced better weight and fat mass reduction, which were beneficial for blood glucose control. Our findings may guide the selection of appropriate drugs for glycemic and weight control.

Trial registration: NCT02325960, registered 25 December 2014.

Keywords: Body composition; Exenatide; Insulin glargine; Type 2 diabetes.

Conflict of interest statement

The study was approved by the ethic committee of Drum Tower Hospital affiliated with Nanjing University Medical School and all participants signed a written consent form.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of the study participants
Fig. 2
Fig. 2
Changes in fat mass and lean tissue in the total body, trunk, limbs, and android and gynoid regions following exenatide treatment

References

    1. Bes-Rastrollo M, Sayon-Orea C, Ruiz-Canela M, Martinez-Gonzalez MA. Impact of sugars and sugar taxation on body weight control: a comprehensive literature review. Obesity. 2016;24:1410–1426. doi: 10.1002/oby.21535.
    1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, Mullany EC, Biryukov S, Abbafati C, Abera SF, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the global burden of disease study 2013. Lancet. 2014;384:766–781. doi: 10.1016/S0140-6736(14)60460-8.
    1. Wright CS, Weinheimer-Haus EM, Fleet JC, Peacock M, Campbell WW. The apparent relation between plasma 25-Hydroxyvitamin D and insulin resistance is largely attributable to central adiposity in overweight and obese adults. J Nutr. 2015;145:2683–2689. doi: 10.3945/jn.115.220541.
    1. 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;62:921–925. doi: 10.1016/j.jacc.2013.06.027.
    1. Tchernof A, Despres JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013;93:359–404. doi: 10.1152/physrev.00033.2011.
    1. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94:311–321. doi: 10.1016/j.diabres.2011.10.029.
    1. McMurray F, Patten DA, Harper ME. Reactive oxygen species and oxidative stress in obesity-recent findings and empirical approaches. Obesity. 2016;24:2301–2310. doi: 10.1002/oby.21654.
    1. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, Davidson MB, Einhorn D, Garvey WT, et al. AACE comprehensive diabetes management algorithm 2013. Endocr Pract. 2013;19:327–336. doi: 10.4158/endp.19.2.a38267720403k242.
    1. Dombrowski SU, Knittle K, Avenell A, Araujo-Soares V, Sniehotta FF. Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. BMJ. 2014;348:g2646. doi: 10.1136/bmj.g2646.
    1. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of diabetes. Diabetes Care. 2015;38:140–149. doi: 10.2337/dc14-2441.
    1. American Diabetes A Standards of medical care in diabetes--2014. Diabetes Care. 2014;37(Suppl 1):S14–S80. doi: 10.2337/dc14-S014.
    1. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of diabetes (EASD) Diabetologia. 2012;55:1577–1596. doi: 10.1007/s00125-012-2534-0.
    1. Ten Kulve JS, Veltman DJ, van Bloemendaal L, Barkhof F, Drent ML, Diamant M, IJ RG. Liraglutide reduces CNS activation in response to visual food cues only after short-term treatment in patients with type 2 diabetes. Diabetes Care. 2016;39:214–221. doi: 10.2337/dc16-1522.
    1. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014;384:2228–2234. doi: 10.1016/S0140-6736(14)61335-0.
    1. Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH, et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014;37:2763–2773. doi: 10.2337/dc14-0876.
    1. Campbell JE, Drucker DJ. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013;17:819–837. doi: 10.1016/j.cmet.2013.04.008.
    1. Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, Hoogwerf BJ, Rosenstock J. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2011;154:103–112. doi: 10.7326/0003-4819-154-2-201101180-00300.
    1. Jendle J, Nauck MA, Matthews DR, Frid A, Hermansen K, During M, Zdravkovic M, Strauss BJ, Garber AJ. Lead et al: weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue. Diabetes Obes Metab. 2009;11:1163–1172. doi: 10.1111/j.1463-1326.2009.01158.x.
    1. Bunck MC, Diamant M, Eliasson B, Corner A, Shaginian RM, Heine RJ, Taskinen MR, Yki-Jarvinen H, Smith U. Exenatide affects circulating cardiovascular risk biomarkers independently of changes in body composition. Diabetes Care. 2010;33:1734–1737. doi: 10.2337/dc09-2361.
    1. Bi Y, Zhang B, Xu W, Yang H, Feng W, Li C, Tong G, Li M, Wang X, Shen S, et al. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes. Acta Diabetol. 2014;51:865–873. doi: 10.1007/s00592-014-0638-3.
    1. Elisha B, Azar M, Taleb N, Bernard S, Iacobellis G, Rabasa-Lhoret R. Body composition and Epicardial fat in type 2 diabetes patients following insulin Detemir versus insulin glargine initiation. Horm Metab Res. 2016;48:42–47.
    1. Packianathan IC, Fuller NJ, Peterson DB, Wright A, Coward WA, Finer N. Use of a reference four-component model to define the effects of insulin treatment on body composition in type 2 diabetes: the 'Darwin study'. Diabetologia. 2005;48:222–229. doi: 10.1007/s00125-004-1642-x.
    1. Drucker DJ, Nauck MA. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. Lancet. 2006;368:1696–1705. doi: 10.1016/S0140-6736(06)69705-5.
    1. Chia CW, Egan JM. Incretin-based therapies in type 2 diabetes mellitus. J Clin Endocrinol Metab. 2008;93:3703–3716. doi: 10.1210/jc.2007-2109.
    1. Vilsboll T, Christensen M, Junker AE, Knop FK, Gluud LL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ. 2012;344:d7771. doi: 10.1136/bmj.d7771.
    1. Cuthbertson DJ, Irwin A, Gardner CJ, Daousi C, Purewal T, Furlong N, Goenka N, Thomas EL, Adams VL, Pushpakom SP, et al. Improved glycaemia correlates with liver fat reduction in obese, type 2 diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One. 2012;7:e50117. doi: 10.1371/journal.pone.0050117.
    1. Sathyanarayana P, Jogi M, Muthupillai R, Krishnamurthy R, Samson SL, Bajaj M. Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity. 2011;19:2310–2315. doi: 10.1038/oby.2011.152.
    1. Shah PK, Mudaliar S, Chang AR, Aroda V, Andre M, Burke P, Henry RR. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes. Diabetes Obes Metab. 2011;13:505–510. doi: 10.1111/j.1463-1326.2011.01370.x.
    1. Zhou BF. Cooperative meta-analysis Group of the Working Group on obesity in C: predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults--study on optimal cut-off points of body mass index and waist circumference in Chinese adults. Biomed Environ Sci. 2002;15:83–96.
    1. Yin TT, Bi Y, Li P, Shen SM, Xiong XL, Gao LJ, Jiang C, Wang Y, Feng WH, Zhu DL. Comparison of glycemic variability in Chinese T2DM patients treated with Exenatide or insulin glargine: a randomized controlled trial. Diabetes Ther. 2018;9:1253–1267. doi: 10.1007/s13300-018-0412-6.
    1. FDA: Guidance for Industry: Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention. https://wwwfdagov/downloads/Drugs//Guidances/ucm071624pdf 2016, Accessed 4 April 2016.
    1. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, Renard E, Russell-Jones D, Philotheou A, Francisco AM, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN basal-bolus type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. Lancet. 2012;379:1489–1497. doi: 10.1016/S0140-6736(12)60204-9.
    1. Russell-Jones D, Khan R. Insulin-associated weight gain in diabetes--causes, effects and coping strategies. Diabetes Obes Metab. 2007;9:799–812. doi: 10.1111/j.1463-1326.2006.00686.x.
    1. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–412. doi: 10.1136/bmj.321.7258.405.
    1. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002;51:2951–2958. doi: 10.2337/diabetes.51.10.2951.
    1. Diamant M, Lamb HJ, van de Ree MA, Endert EL, Groeneveld Y, Bots ML, Kostense PJ, Radder JK. The association between abdominal visceral fat and carotid stiffness is mediated by circulating inflammatory markers in uncomplicated type 2 diabetes. J Clin Endocrinol Metab. 2005;90:1495–1501. doi: 10.1210/jc.2004-1579.
    1. 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;28:1039–1049. doi: 10.1161/ATVBAHA.107.159228.
    1. Rojas JM, Printz RL, Niswender KD. Insulin detemir attenuates food intake, body weight gain and fat mass gain in diet-induced obese Sprague-Dawley rats. Nutr Diabetes. 2011;1:e10. doi: 10.1038/nutd.2011.6.
    1. Zafar MI, Hu C, Liu D, Shafqat RA, Gao F. Insulin detemir causes lesser weight gain in comparison to insulin glargine: role on hypothalamic NPY and galanin. J Diabetes Res. 2014;2014:458104. doi: 10.1155/2014/458104.
    1. Vehkavaara S, Yki-Jarvinen H. 3.5 years of insulin therapy with insulin glargine improves in vivo endothelial function in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2004;24:325–330. doi: 10.1161/01.ATV.0000113817.48983.c5.
    1. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab. 2000;278:E941–E948. doi: 10.1152/ajpendo.2000.278.5.E941.
    1. Preis SR, Massaro JM, Robins SJ, Hoffmann U, Vasan RS, Irlbeck T, Meigs JB, Sutherland P, D'Agostino RB, Sr, O'Donnell CJ, et al. Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham heart study. Obesity. 2010;18:2191–2198. doi: 10.1038/oby.2010.59.
    1. Bunck MC, Diamant M, Corner A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009;32:762–768. doi: 10.2337/dc08-1797.

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