Comparison of Exenatide and Metformin Monotherapy in Overweight/Obese Patients with Newly Diagnosed Type 2 Diabetes

Jia Liu, Yanjin Hu, Yuan Xu, Yumei Jia, Li Miao, Guang Wang, Jia Liu, Yanjin Hu, Yuan Xu, Yumei Jia, Li Miao, Guang Wang

Abstract

Aims: The present study assessed the therapeutic effect of exenatide and metformin as the initial therapy on overweight/obese patients with newly diagnosed type 2 diabetes (T2D).

Methods: The prospective, nonrandomized, interventional study enrolled a total of 230 overweight or obese patients with newly diagnosed T2D who were administrated exenatide or metformin hydrochloride for 12 weeks.

Results: 224/230 patients, including 106 in the exenatide group and 118 in the metformin group, completed the 12-week treatment. Both exenatide and metformin significantly decreased the HbA1c levels in overweight/obese patients with newly diagnosed T2D (all P < 0.05). The reduction in HbA1c and the proportion of patients with HbA1c < 7.0% (53 mmol/mol) were higher in the exenatide group than in the metformin group (all P < 0.05). The exenatide treatment caused a greater decline in the body weight and BMI as compared to the metformin treatment (all P < 0.01). The exenatide treatment (β = 0.41, P < 0.01) and baseline HbA1c level (β = -0.84, P < 0.01) were independent influencing factors for the decrease in HbA1c level.

Conclusions: For an initial therapy in overweight/obese patients with newly diagnosed T2D, exenatide causes a better glycemic control than metformin. This trial is registered with NCT03297879.

References

    1. Guariguata L., Whiting D. R., Hambleton I., Beagley J., Linnenkamp U., Shaw J. E. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Research and Clinical Practice. 2014;103(2):137–149. doi: 10.1016/j.diabres.2013.11.002.
    1. Garber A. J. Obesity and type 2 diabetes: which patients are at risk? Diabetes, Obesity and Metabolism. 2012;14(5):399–408. doi: 10.1111/j.1463-1326.2011.01536.x.
    1. American Diabetes Association. Standards of medical care in diabetes—2013. Diabetes Care. 2013;36(Supplement 1):S11–S66. doi: 10.2337/dc13-S011.
    1. Derosa G., Franzetti I. G., Querci F., et al. Exenatide plus metformin compared with metformin alone on β-cell function in patients with type 2 diabetes. Diabetic Medicine. 2012;29(12):1515–1523. doi: 10.1111/j.1464-5491.2012.03699.x.
    1. Diamant M., Van Gaal L., Guerci B., et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. The Lancet Diabetes and Endocrinology. 2014;2(6):464–473. doi: 10.1016/S2213-8587(14)70029-4.
    1. Buse J. B., Rosenstock J., Sesti G., et al. 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) The Lancet. 2009;374(9683):39–47. doi: 10.1016/S0140-6736(09)60659-0.
    1. Chinese Society of Endocrinology. Chinese expert consensus for the prevention and treatment of obesity in adults. 2011;27:711–717. doi: 10.3760/cma.j.issn.1000-6699.2011.09.003.
    1. Bermudez V., Cano R., Cano C., et al. Homeostasis model assessment (HOMA) as surrogate insulinization criteria in patients with type 2 diabetes. American Journal of Therapeutics. 2008;15(4):409–416. doi: 10.1097/MJT.0b013e318160b909.
    1. Wang G., Liu J., Yang N., et al. MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients. PLoS One. 2014;9(8, article e105698) doi: 10.1371/journal.pone.0105698.
    1. Russell-Jones D., Cuddihy R. M., Hanefeld M., et al. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study. Diabetes Care. 2012;35(2):252–258. doi: 10.2337/dc11-1107.
    1. Cotter A. P., Durant N., Agne A. A., Cherrington A. L. Internet interventions to support lifestyle modification for diabetes management: a systematic review of the evidence. Journal of Diabetes and its Complications. 2014;28(2):243–251. doi: 10.1016/j.jdiacomp.2013.07.003.
    1. Drucker D. J., Nauck M. A. The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. The Lancet. 2006;368(9548):1696–1705. doi: 10.1016/S0140-6736(06)69705-5.
    1. Kim Y. G., Hahn S., Oh T. J., Park K. S., Cho Y. M. Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis. Diabetes, Obesity & Metabolism. 2014;16(10):900–909. doi: 10.1111/dom.12293.
    1. Cho Y. M. Incretin physiology and pathophysiology from an Asian perspective. Journal of Diabetes Investigation. 2015;6(5):495–507. doi: 10.1111/jdi.12305.
    1. Oh T. J., Kim M. Y., Shin J. Y., et al. The incretin effect in Korean subjects with normal glucose tolerance or type 2 diabetes. Clinical Endocrinology. 2014;80(2):221–227. doi: 10.1111/cen.12167.
    1. Herman W. H., Dungan K. M., Wolffenbuttel B. H. R., et al. Racial and ethnic differences in mean plasma glucose, hemoglobin A1c, and 1,5-anhydroglucitol in over 2000 patients with type 2 diabetes. The Journal of Clinical Endocrinology &Metabolism. 2009;94(5):1689–1694. doi: 10.1210/jc.2008-1940.
    1. Esposito K., Chiodini P., Bellastella G., Maiorino M. I., Giugliano D. Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients. Diabetes, Obesity & Metabolism. 2012;14(3):228–233. doi: 10.1111/j.1463-1326.2011.01512.x.
    1. Knowler W. C., Barrett-Connor E., Fowler S. E., et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. The New England Journal of Medicine. 2002;346(6):393–403. doi: 10.1056/NEJMoa012512.
    1. Thondam S. K., Cross A., Cuthbertson D. J., Wilding J. P., Daousi C. Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with type 2 diabetes mellitus. Diabetic Medicine. 2012;29(8):e205–e210. doi: 10.1111/j.1464-5491.2012.03675.x.
    1. Mannucci E., Ognibene A., Cremasco F., et al. Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Diabetes Care. 2001;24(3):489–494. doi: 10.2337/diacare.24.3.489.
    1. de Oliveira E. P., Diegoli A. C., Corrente J. E., McLellan K. C., Burini R. C. The increase of dairy intake is the main dietary factor associated with reduction of body weight in overweight adults after lifestyle change program. Nutrición Hospitalaria. 2015;32(3):1042–1049. doi: 10.3305/nh.2015.32.3.9345.
    1. Sene-Fiorese M., Duarte F. O., de Aquino Junior A. E., et al. The potential of phototherapy to reduce body fat, insulin resistance and “metabolic inflexibility” related to obesity in women undergoing weight loss treatment. Lasers in Surgery and Medicine. 2015;47(8):634–642. doi: 10.1002/lsm.22395.
    1. Batchuluun B., Inoguchi T., Sonoda N., et al. Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells. Atherosclerosis. 2014;232(1):156–164. doi: 10.1016/j.atherosclerosis.2013.10.025.
    1. Barazzoni R., Zanetti M., Gortan Cappellari G., et al. Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increasing mitochondrial reactive oxygen species (ROS) generation and nuclear factor-κB inhibitor (IκB)–nuclear factor-κB (NFκB) activation in rat muscle, in the absence of mitochondrial dysfunction. Diabetologia. 2012;55(3):773–782. doi: 10.1007/s00125-011-2396-x.
    1. Morimoto A., Tatsumi Y., Deura K., et al. Impact of impaired insulin secretion and insulin resistance on the incidence of type 2 diabetes mellitus in a Japanese population: the Saku study. Diabetologia. 2013;56(8):1671–1679. doi: 10.1007/s00125-013-2932-y.
    1. Retnakaran R., Zinman B. Short-term intensified insulin treatment in type 2 diabetes: long-term effects on β-cell function. Diabetes, Obesity & Metabolism. 2012;14(Supplement 3):161–166. doi: 10.1111/j.1463-1326.2012.01658.x.
    1. Zander M., Madsbad S., Madsen J. L., Holst J. J. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and β-cell function in type 2 diabetes: a parallel-group study. The Lancet. 2002;359(9309):824–830. doi: 10.1016/S0140-6736(02)07952-7.
    1. Bunck M. C., Corner A., Eliasson B., et al. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care. 2011;34(9):2041–2047. doi: 10.2337/dc11-0291.
    1. Buteau J., Spatz M. L., Accili D. Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic β-cell mass. Diabetes. 2006;55(5):1190–1196. doi: 10.2337/db05-0825.
    1. Zhang L., Wang Y., Wang J., Liu Y., Yin Y. Protein kinase C pathway mediates the protective effects of glucagon-like peptide-1 on the apoptosis of islet β-cells. Molecular Medicine Reports. 2015;12(5):7589–7594. doi: 10.3892/mmr.2015.4355.

Source: PubMed

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