ประสิทธิภาพของยากลุ่มยากระตุ้นตัวรับเปปไทด์ตัวเหมือนกลูคากอนชนิดที่ 1 ต่อ ดัชนีมวลกายและเส้นรอบเอวในผู้ป่วยโรคอ้วนหรือน้ำหนักตัวเกิน: การทบทวนวรรณกรรมอย่างเป็นระบบและการวิเคราะห์อภิมานเครือข่าย
Article Sidebar
Main Article Content
บทคัดย่อ
วัตถุประสงค์: เพื่อประเมินประสิทธิภาพของยากระตุ้นตัวรับเปปไทด์ตัวเหมือนกลูคากอนชนิดที่ 1 (glucagon-like peptide 1 receptor agonists หรือ GLP-1 receptor agonists) ในการลดดัชนีมวลกายและเส้นรอบเอว วิธีการ: การศึกษานี้เป็นการทบทวนวรรณกรรมอย่างเป็นระบบและการวิเคราะห์อภิมานเครือข่ายจากงานวิจัยการทดลองแบบสุ่มที่มีกลุ่มควบคุมในผู้ที่มีภาวะอ้วนหรือมีน้ำหนักตัวเกินทั้งที่เป็นและไม่เป็นเบาหวานชนิดที่ 2 ที่ใช้ GLP-1 receptor agonists ผลลัพธ์การศึกษาหลัก คือ ดัชนีมวลกายและเส้นรอบเอว ผลการศึกษา: โดยภาพรวม GLP-1 receptor agonists สามารถลดดัชนีมวลกายและเส้นรอบเอวอย่างมีนัยสำคัญเมื่อเทียบกับยาหลอก พบว่า tirzepatide ลดดัชนีมวลกายได้มากที่สุดที่ระยะเวลามากกว่า 24 ถึง 52 สัปดาห์ โดยมีความแตกต่างของค่าเฉลี่ย (mean difference: MD) = -3.58 ( 95%CI : -4.68, -2.47) ตามด้วย semaglutide ทั้งชนิดฉีดเข้าใต้ผิวหนังและชนิดรับประทาน ส่วนที่ระยะเวลานานกว่า 52 สัปดาห์ semaglutide รูปแบบรับประทานลดดัชนีมวลกายได้มากที่สุด (MD -4.70; 95%CI: -6.72, -2.68) ส่วนการลดเส้นรอบเอว tirzepatide, semaglutide รูปแบบฉีดเข้าใต้ผิวหนัง และ semaglutide รูปแบบรับประทาน ลดได้มากที่สุด โดย semaglutide รูปแบบฉีดเข้าใต้ผิวหนัง ลดเส้นรอบเอวได้มากสุดในช่วง 12-24 สัปดาห์ โดยลดลงได้ 9.3 เซนติเมตร (95%CI: -14.61,-3.99) และ tirzepatide ลดเส้นรอบเอวได้มากสุดที่ระยะเวลามากกว่า 24 สัปดาห์ โดยลดได้ 12.74 เซนติเมตร (95%CI: -16.57,-8.90) เมื่อระยะเวลานานกว่า 52 สัปดาห์ ซึ่งสอดคล้องกับน้ำหนักตัวและดัชนีมวลกายที่ลดลง สรุป: ยากลุ่ม GLP-1 receptor agonists โดยเฉพาะ tirzepatide และ semaglutide มีประสิทธิภาพสูงในการลดดัชนีมวลกายและเส้นรอบเอวทั้งในผู้ที่เป็นและไม่เป็นเบาหวานชนิดที่ 2 ข้อมูลที่ได้จากการศึกษานี้สามารถเป็นแนวทางสำหรับการเลือกใช้ยาเพื่อลดน้ำหนัก
Article Details
อนุญาตภายใต้เงื่อนไข Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
ผลการวิจัยและความคิดเห็นที่ปรากฏในบทความถือเป็นความคิดเห็นและอยู่ในความรับผิดชอบของผู้นิพนธ์ มิใช่ความเห็นหรือความรับผิดชอบของกองบรรณาธิการ หรือคณะเภสัชศาสตร์ มหาวิทยาลัยสงขลานครินทร์ ทั้งนี้ไม่รวมความผิดพลาดอันเกิดจากการพิมพ์ บทความที่ได้รับการเผยแพร่โดยวารสารเภสัชกรรมไทยถือเป็นสิทธิ์ของวารสารฯ
เอกสารอ้างอิง
Medical Technology Assessment and Research Institute, Department of Medical Services, Ministry of Public Health. Guidelines for medical practice to prevent and treat obesity [online]. 2010 [cited Aug 20, 2023]. Available from: www.imrta.dms.moph.go. th/imrta/images/pdf_cpg/2553/53-4.pdf
Division of Noncommunicable Diseases, Department of Disease Control. One-thirds of working-age Thais are “obese” and what to do? Stay away from obesity [online]. 2024 [cited Oct 16, 2024]. Available from: ddc.moph.go.th/dncd/forecast_detail.php?publish=15407&deptcode=dncd.
World Health Organization. Obesity and overweight [online]. 2024 [cited Oct 16, 2024]. Available from: www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
Jin X, Qiu T, Li L, Yu R, Chen X, Li C, et al. Pathophy- siology of obesity and its associated diseases. Acta Pharm Sin B. 2023; 13: 2403-24.
Dhawan D, Sharma S. Abdominal obesity, adipokines and non-communicable diseases. J Steroid Biochem Mol Biol. 2020; 203: 105737.
Grunvald E, Shah R, Hernaez R, Chandar AK, Pickett-Blakely O, Teigen LM, et al. AGA Clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology 2022; 163: 1198–225.
American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2022.Diabetes Care 2022;45(Suppl 1):S17-S38. doi: 10.2337/dc22-S002.
Wilding JP. The importance of weight management in type 2 diabetes mellitus. Int J Clin Pract. 2014; 68: 682-91. doi: 10.1111/ijcp.12384.
Zeng Y, Wu Y, Zhang Q, Xiao X. Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio 2024; 15: e0203223. doi: 10.1128/mbio.02032-23.
Singh K, Aulakh SK, Nijjar GS, Singh S, Sandhu APS, Luthra S, et al. Rebalancing the gut: Glucagon-like peptide-1 agonists as a strategy for obesity and metabolic health. Cureus. 2024; 16: e64738.
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab 2018; 27: 740–56.
Filippatos TD, Panagiotopoulou TV, Elisaf MS. Adverse effects of GLP-1 receptor agonists. Rev Diabet Stud. 2014; 11: 202–30.
Tan HCQ, Dampil OA, Marquez MM. Efficacy and safety of semaglutide for weight loss in obesity without diabetes: a systematic review and meta-analysis. J Asean Fed Endocr Soc. 2022; 37: 65–72.
Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Villegas ECM, et al. PIONEER 1: randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care. 2019; 42: 1724–32.
Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 402: 705–19.
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015; 373: 11–22.
Frias JP, Bonora E, Ruiz LN, Li YG, Yu Z, Milicevic Z, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care. 2021; 44: 765–73.
Rodgers M, Migdal AL, Rodríguez TG, Chen ZZ, Nath AK, Gerszten RE, et al. Weight loss outcomes among early high responders to exenatide treatment: a randomized, placebo-controlled study in overweight and obese women. Front Endocrinol (Lausanne). 2021; 12: 742873.
Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013; 15: 1000–7.
Alkhezi OS, Alahmed AA, Alfayez OM, Alzuman OA, Almutairi AR, Almohammed OA. Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: a network meta-analysis of randomized clinical trials. Obes Rev 2023; 24: e13543. doi: 10.1111/obr.13543.
Ross R, Neeland IJ, Yamashita S, Shai I, Seidell J, Magni P, et al. Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nat Rev Endocrinol. 2020; 16: 177–89.
Haufs MG, Zöllner YF. Waist–hip ratio more appropriate than body mass index. Dtsch Arztebl Int 2020; 117: 659. doi: 10.3238/arztebl.2020.0659a.
Atlas SJ, Kim K, Nhan E, Touchette DR, Moradi A, Agboola F, Rind DM, Beaudoin FL, Pearson SD. Medications for obesity management: Effectiveness and value. J Manag Care Spec Pharm. 2023 ; 29: 569-75. doi: 10.18553/jmcp.2023.29.5.569.
Sarma S, Palcu P. Weight loss between glucagon-like peptide-1 receptor agonists and bariatric surgery in adults with obesity: a systematic review and meta-analysis. Obesity (Silver Spring). 2022; 30: 2111–21.
Wongtangprasert S, Dilokthornsakul P. Network meta-analysis: the concept and its applications for healthcare professionals. Ramathibodi Medical Journal 2017; 40: 40-58.
Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011; 343: d5928.
Takeshima N, Sozu T, Tajika A, Ogawa Y, Hayasaka Y, Furukawa TA. Which is more generalizable, powerful and interpretable in meta-analyses, mean difference or standardized mean difference? BMC Med Res Methodol. 2014; 14: 30.
Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012; 3: 80–97.
Mbuagbaw L, Rochwerg B, Jaeschke R, Heels-Andsell D, Alhazzani W, Thabane L, et al. Approaches to interpreting and choosing the best treatments in network meta-analyses. Syst Rev. 2017; 6: 79.
Brignardello-Petersen R, Florez ID, Izcovich A, Santesso N, Hazlewood G, Alhazzani W, et al. GRADE approach to drawing conclusions from a network meta-analysis using a minimally contextualised framework. BMJ 2020; 371: m3904.
Myrskyla M, Chang VW. Weight change, initial BMI, and mortality among middle- and older-aged adults. Epidemiology. 2009; 20: 840–8.
Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005; 28: 1083-91. doi: 10.2337/diacare.28.5.1083.
Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023; 402: 613–26.
Wharton S, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5. Obesity (Silver Spring). 2023; 31: 703–15.
Wang W, Yan X, Cheng Z, Zhang Q, Wang R, Deng Y, et al. Efficacy and safety of adding once-weekly dulaglutide to basal insulin for inadequately controlled type 2 diabetes in Chinese patients (AWARD-CHN3): a randomized, double-blind, placebo-controlled, phase III trial. Diabetes Obes Metab. 2023; 25: 3690–9.
Kimura T, Katakura Y, Shimoda M, Kawasaki F, Yamabe M, Tatsumi F, et al. Comparison of clinical efficacy and safety of weekly glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in Japanese patients with type 2 diabetes: randomized, parallel-group, multicentre, open-label trial (COMING study). Diabetes Obes Metab. 2023; 25: 3632–47.
Yabe D, Kawamori D, Seino Y, Oura T, Takeuchi M. Change in pharmacodynamic variables following once-weekly tirzepatide treatment versus dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono substudy). Diabetes Obes Metab. 2023; 25: 398–406.
Iijima T, Shibuya M, Ito Y, Terauchi Y. Effects of switching from liraglutide to semaglutide or dulaglutide in patients with type 2 diabetes: a randomized controlled trial. J Diabetes Investig. 2023; 14: 774–81.
Mok J, Adeleke MO, Brown A, Magee CG, Firman C, Makahamadze C, et al. Safety and efficacy of liraglutide, 3.0 mg, once daily vs placebo in patients with poor weight loss following metabolic surgery: the BARI-OPTIMISE randomized clinical trial. JAMA Surg. 2023; 158: 1003–11.
Takahashi Y, Nomoto H, Yokoyama H, Takano Y, Nagai S, Tsuzuki A, et al. Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: a multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study). Diabetes Obes Metab. 2023; 25: 1503–11.
Aroda VR, Aberle J, Bardtrum L, Christiansen E, Knop FK, Gabery S, et al. Efficacy and safety of once-daily oral semaglutide 25 mg and 50 mg compared with 14 mg in adults with type 2 diabetes (PIONEER PLUS): a multicentre, randomised, phase 3b trial. Lancet. 2023; 402: 693–704.
Knop FK, Aroda VR, do Vale RD, Holst-Hansen T, Laursen PN, Rosenstock J, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2023; 402: 705–19.
Yabe D, Nakamura J, Kaneto H, Deenadayalan S, Navarria A, Gislum M, Inagaki N; PIONEER 10 Investigators. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020; 8: 392-406. doi: 10.1016/S2213-8587(20)30074-7.
Zinman B, Bhosekar V, Busch R, Holst I, Ludvik B, Thielke D, et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2019; 7: 356–67.
Zinman B, Hoogwerf BJ, Durá García S, Milton DR, Giaconia JM, Kim DD, et al. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2007; 146: 477-85.
Zinman B, Aroda VR, Buse JB, Cariou B, Harris SB, Hoff ST, et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: the PIONEER 8 trial. Diabetes Care. 2019; 42: 2262–71.
Pan C, Han P, Liu X, Yan S, Feng P, Zhou Z, et al. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). Diabetes Metab Res Rev. 2014; 30: 726–35.
Yang W, Min K, Zhou Z, Li L, Xu XJ, Zhu D, et al. Efficacy and safety of lixisenatide in a predominantly Asian population with type 2 diabetes insufficiently controlled with basal insulin: the GetGoal-L-C randomized trial. Diabetes Obes Metab. 2018; 20: 335–43.
Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021; 384: 989–1002.
Yamada Y, Katagiri H, Hamamoto Y, Deenadayalan S, Navarria A, Nishijima K, et al. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020; 8: 377–91.
Wysham CH, Rosenstock J, Vetter ML, Dong F, Öhman P, Iqbal N. Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes. Diabetes Obes Metab. 2018; 20: 165–72.
Wysham CH, MacConell L, Hardy E. Efficacy and safety of multiple doses of exenatide once-monthly suspension in patients with type 2 diabetes: A phase II randomized clinical trial. Diabetes Care. 2016; 39: 1768–76.
Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care. 2014; 37: 2159–67.
Weghuber D, Forslund A, Ahlström H, Alderborn A, Bergström K, Brunner S, et al. A 6-month randomized, double-blind, placebo-controlled trial of weekly exenatide in adolescents with obesity. Pediatr Obes 2020; 15: e12624.
Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK, et al. Once-weekly semaglutide in adolescents with obesity. N Engl J Med 2022; 387: 2245–57.
Wadden TA, Walsh OA, Berkowitz RI, Chao AM, Alamuddin N, Gruber K, et al. Intensive behavioral therapy for obesity combined with liraglutide 3.0 mg: a randomized controlled trial. Obesity. 2019; 27: 75–86.
Wadden TA, Hollander P, Klein S, Niswender K, Woo V, Hale PM, et al. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study. Int J Obes 2013; 37: 1443–51.
Wadden TA, Tronieri JS, Sugimoto D, Lund MT, Auerbach P, Jensen C, et al. Liraglutide 3.0 mg and intensive behavioral therapy (IBT) for obesity in primary care: the SCALE IBT randomized controlled trial. Obesity. 2020; 28: 529–36.
Rodgers M, Migdal AL, Rodríguez TG, Chen ZZ, Nath AK, Gerszten RE, et al. Weight loss outcomes among early high responders to exenatide treatment: a randomized, placebo controlled study in overweight and obese women. Front Endocrinol (Lausanne). 2021; 12: 742873.
Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, et al. Effect of subcutaneous semaglutide vs placebo as an adjunct to intensive behavioral therapy on body weight in adults with overweight or obesity: the STEP 3 randomized clinical trial. JAMA. 2021; 325: 1403–13.
Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022; 28: 2083–91.
Blackman A, Foster GD, Zammit G, Rosenberg R, Aronne L, Wadden T, et al. Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial. Int J Obes. 2016; 40: 1310–9.
Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of adding liraglutide vs placebo to a high-dose insulin regimen in patients with type 2 diabetes: a randomized clinical trial. JAMA Intern Med. 2016; 176: 939–47.
Tamborlane WV, Barrientos-Pérez M, Fainberg U, Frimer-Larsen H, Hafez M, Hale PM, et al. Liraglutide in children and adolescents with type 2 diabetes. N Engl J Med. 2019; 381: 637–46.
Sorli C, Harashima S, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017; 5: 251–60.
Roth CL, Perez FA, Whitlock KB, Elfers C, Yanovski JA, Shoemaker AH, et al. A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity. Diabetes Obes Metab. 2021; 23: 363–73.
Skrivanek Z, Gaydos BL, Chien JY, Geiger MJ, Heathman MA, Berry S, et al. Dose-finding results in an adaptive, seamless, randomized trial of once-weekly dulaglutide combined with metformin in type 2 diabetes patients (AWARD-5). Diabetes Obes Metab. 2014; 16: 748–56.
Seino Y, Min KW, Niemoeller E, Takami A, Abe N, Arai K, et al. Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). Diabetes Obes Metab. 2012; 14: 910–7.
Rubino DM, Greenway FL, Khalid U, O’Neil PM, Rosenstock J, Sørrig R, et al. Effect of weekly subcutaneous semaglutide vs daily liraglutide on body weight in adults with overweight or obesity without diabetes: the STEP 8 randomized clinical trial. JAMA. 2022; 327: 138–50.
Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021; 325: 1414–25.
Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021; 398: 143–55.
Rosenstock J, Raccah D, Koranyi L, Maffei L, Boka G, Miossec P, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013; 36: 2945–51.
Rosenstock J, Klaff LJ, Schwartz S, Northrup J, Holcombe JH, Wilhelm K, et al. Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without pre-diabetes. Diabetes Care. 2010; 33: 1173–5.
Rodbard HW, Lingvay I, Reed J, De La Rosa R, Rose L, Sugimoto D, et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018; 103: 2291–301.
Riddle MC, Aronson R, Home P, Marre M, Niemoeller E, Miossec P, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). Diabetes Care. 2013; 36: 2489–96.
Ratner RE, Rosenstock J, Boka G. Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial. Diabet Med. 2010; 27: 1024–32.
Nauck M, Rizzo M, Johnson A, Bosch-Traberg H, Madsen J, Cariou B. Once-daily liraglutide versus lixisenatide as add-on to metformin in type 2 diabetes: a 26-week randomized controlled clinical trial. Diabetes Care. 2016; 39: 1501–9.
Pratley R, Amod A, Hoff ST, Kadowaki T, Lingvay I, Nauck M, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019; 394: 39–50.
Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018; 6: 275–86.
Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013; 15: 1000–7.
Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015; 373: 11–22.
Nauck MA, Petrie JR, Sesti G, Mannucci E, Courrèges JP, Lindegaard ML, et al. A phase 2, randomized, dose-finding study of the novel once-weekly human GLP-1 analog, semaglutide, compared with placebo and open-label liraglutide in patients with type 2 diabetes. Diabetes Care. 2016; 39: 231–41.
Odawara M, Miyagawa J, Iwamoto N, Takita Y, Imaoka T, Takamura T. Once-weekly glucagon-like peptide-1 receptor agonist dulaglutide significantly decreases glycated haemoglobin compared with once-daily liraglutide in Japanese patients with type 2 diabetes: 52 weeks of treatment in a randomized phase III study. Diabetes Obes Metab. 2016; 18: 249–57.
O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, et al. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018; 392: 637–49.
Mosenzon O, Blicher TM, Rosenlund S, Eriksson JW, Heller S, Hels OH, et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019; 7: 515–27.
MacConell LA, Okerson T, Wolka AM, Brodows RG, Francisco S. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther. 2008; 30: 751–9.
Mensberg P, Nyby S, Jørgensen PG, Storgaard H, Jensen MT, Sivertsen J, et al. Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes. Diabetes Obes Metab. 2017; 19: 172–80.
Ludvik B, Frías JP, Tinahones FJ, Wainstein J, Jiang H, Robertson KE, et al. Dulaglutide as add-on therapy to SGLT2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2018; 6: 370–81.
Lingvay I, Desouza CV, Lalic KS, Rose L, Hansen T, Zacho J, et al. A 26-week randomized controlled trial of semaglutide once daily versus liraglutide and placebo in patients with type 2 diabetes suboptimally controlled on diet and exercise with or without metformin. Diabetes Care. 2018; 41: 1926–37.
Le Roux CW, Astrup AV, Fujioka K, Greenway F, Lau DCW, Van Gaal L, et al. Three years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017; 389: 1399–409.
Kim SH, Abbasi F, Lamendola C, Liu A, Ariel D, Schaaf P, et al. Benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. Diabetes Care. 2013; 36: 3276–82.
Kim D, MacConell L, Zhuang D, Kothare PA, Trautmann M, Fineman M, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007; 30: 1487–93.
Kelly AS, Rudser KD, Nathan BM, Fox CK, Metzig AM, Coombes BJ, et al. The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity. JAMA Pediatr. 2013; 167: 355–60.
Kelly AS, Metzig AM, Rudser KD, Fitch AK, Fox CK, Nathan BM, et al. Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study. Obesity. 2012; 20: 364–70.
Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, et al. A randomized, controlled trial of liraglutide for adolescents with obesity. N Engl J Med. 2020; 382: 2117–28.
Kadowaki T, Chin R, Ozeki A, Imaoka T, Ogawa Y. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type 2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes Endocrinol 2022; 10: 634–44.
Kadowaki T, Namba M, Imaoka T, Yamamura A, Goto W, Boardman MK, et al. Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks. J Diabetes Investig. 2011; 2: 210–7.
Kadowaki T, Isendahl J, Khalid U, Lee SY, Nishida T, Ogawa W, et al. Semaglutide once a week in adults with overweight or obesity, with or without type 2 diabetes in an East Asian population (STEP 6): a randomised, double-blind, double-dummy, placebo-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2022; 10: 193–206.
Joubert M, Opigez V, Pavlikova B, Peyro Saint Paul L, Jeandidier N, Briant AR, et al. Efficacy and safety of exenatide as add-on therapy for patients with type 2 diabetes with an intensive insulin regimen: A randomized double-blind trial. Diabetes Obes Metab. 2021; 23: 374–81.
Ji L, Du Y, Xu M, Zhou X, Mo Z, Ma J, et al. Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study. Diabetologia. 2021; 64: 1066–78.
Jensterle M, Ferjan S, Vovk A, Battelino T, Rizzo M, Janež A. Semaglutide reduces fat accumulation in the tongue: A randomized single-blind, pilot study. Diabetes Res Clin Pract. 2021; 178:108935. doi: 10.1016/j.diabres.2021.108935.
Ishøy PL, Knop FK, Broberg BV, Bak N, Andersen UB, Jørgensen NR, et al. Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia: a randomized, placebo-controlled trial. Diabetes Obes Metab. 2017; 19: 162–71.
Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022; 387: 205–16.
Yukiko HI, Tomonori O, Takeuchi OM. Once-weekly dulaglutide with insulin therapy for type 2 diabetes: efficacy and safety results from a Phase 4, randomized, placebo-controlled study. Diabetes Ther 2020; 11: 133-45. doi: 10.1007/s13300-019-00726-8.
Inagaki N, Takeuchi M, Oura T, Imaoka T, Seino Y. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes (SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022; 10: 623–33.
Friedrichsen M, Breitschaft A, Tadayon S, Wizert A, Skovgaard D. The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Diabetes Obes Metab. 2021; 23: 754–62.
Guja C, Frías JP, Somogyi A, Jabbour S, Wang H, Hardy E, et al. Effect of exenatide QW or placebo, both added to titrated insulin glargine, in uncontrolled type 2 diabetes: The DURATION-7 randomized study. Diabetes Obes Metab. 2018; 20: 1602–14.
Gudbergsen H, Overgaard A, Henriksen M, Wæhrens EE, Bliddal H, Christensen R, et al. Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: A randomized controlled trial. Am J Clin Nutr. 2021; 113: 314–23.
Grunberger G, Chang A, Garcia Soria G, Botros FT, Bsharat R, Milicevic Z. Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with type 2 diabetes: Dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study. Diabet Med. 2012; 29: 1260–7.
Gibbons C, Blundell J, Tetens Hoff S, Dahl K, Bauer R, Bækdal T. Effects of oral semaglutide on energy intake, food preference, appetite, control of eating, and body weight in subjects with type 2 diabetes. Diabetes Obes Metab. 2021; 23: 581–8.
Ghanim H, Batra M, Green K, Abuaysheh S, Hejna J, Makdissi A, et al. Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26-week randomized controlled trial; mechanisms of weight loss. Diabetes Obes Metab. 2020; 22: 1742–52.
Garvey WT, Birkenfeld AL, Dicker D, Mingrone G, Pedersen SD, Satylganova A, et al. Efficacy and safety of liraglutide 3.0 mg in individuals with overweight or obesity and type 2 diabetes treated with basal insulin: The SCALE insulin randomized controlled trial. Diabetes Care. 2020; 43: 1085–93.
Gao Y, Yoon KH, Chuang LM, Mohan V, Ning G, Shah S, et al. Efficacy and safety of exenatide in patients of Asian descent with type 2 diabetes inadequately controlled with metformin or metformin and a sulphonylurea. Diabetes Res Clin Pract. 2009 ; 83: 69–76.
Gadde KM, Vetter ML, Iqbal N, Hardy E, Öhman P. Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION-NEO-2 randomized clinical study. Diabetes Obes Metab. 2017; 19: 979–88.
Frías JP, Wynne AG, Matyjaszek-Matuszek B, Bartaskova D, Cox DA, Woodward B, et al. Efficacy and safety of an expanded dulaglutide dose range: A phase 2, placebo-controlled trial in patients with type 2 diabetes using metformin. Diabetes Obes Metab. 2019; 21: 2048–57.
Frías JP, Nauck MA, Van J, Benson C, Bray R, Cui X, et al. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes Metab. 2020; 22: 938–46.
Dungan KM, Povedano ST, Forst T, González JGG, Atisso C, Sealls W, et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): A randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014; 384: 1349–57.
Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021 ; 385: 503–15.
Frías JP, Bonora E, Ruiz LN, Li YG, Yu Z, Milicevic Z, et al. Efficacy and safety of dulaglutide 3.0 mg and 4.5 mg versus dulaglutide 1.5 mg in metformin-treated patients with type 2 diabetes in a randomized controlled trial (AWARD-11). Diabetes Care 2021; 44: 765–73.
Frías JP, Auerbach P, Bajaj HS, Fukushima Y, Lingvay I, Macura S, et al. Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. Lancet Diabetes Endocrinol. 2021; 9: 563–74.
Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: A randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012; 35: 1225–31.
Fox CK, Clark JM, Rudser KD, Ryder JR, Gross AC, Nathan BM, et al. Exenatide for weight-loss maintenance in adolescents with severe obesity: A randomized, placebo-controlled trial. Obesity. 2022; 30: 1105–15.
Dushay J, Gao C, Gopalakrishnan GS, Crawley M, Mitten EK, Wilker E, et al. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care. 2012; 35: 4–11.
Elkind-Hirsch KE, Chappell N, Shaler D, Storment J, Bellanger D. Liraglutide 3 mg on weight, body composition, and hormonal and metabolic parameters in women with obesity and polycystic ovary syndrome: a randomized placebo-controlled-phase 3 study. Fertil Steril. 2022; 118: 371–81.
Dungan KM, Weitgasser R, Perez Manghi F, Pintilei E, Fahrbach JL, Jiang HH, et al. A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (AWARD-8). Diabetes Obes Metab. 2016; 18: 475–82.
Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008; 372: 39.
Diene G, Angulo M, Hale PM, Jepsen CH, Hofman PL, Hokken-Koelega A, et al. Liraglutide for weight management in children and adolescents with Prader-Willi syndrome and obesity. J Clin Endocrinol Metab. 2023; 108: 4–12.
Defronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of Exenatide (Exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005; 28: 1255–61.
Davies MJ, Bain SC, Atkin SL, Rossing P, Scott D, Shamkhalova MS, et al. Efficacy and safety of liraglutide versus placebo as add-on to glucose-lowering therapy in patients with type 2 diabetes and moderate renal impairment (LIRA-RENAL): A randomized clinical trial. Diabetes Care. 2016; 39: 222–30.
Davies M, Færch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, et al. Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021; 397: 971–84.
Davies MJ, Bergenstal R, Bode B, Kushner RF, Lewin A, Skjøth TV, et al. Efficacy of liraglutide for weight loss among patients with type 2 diabetes: The SCALE diabetes randomized clinical trial. JAMA. 2015; 314: 687–99.
Davies M, Pieber TR, Hartoft-Nielsen ML, Hansen OKH, Jabbour S, Rosenstock J. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: A randomized clinical trial. JAMA. 2017; 318: 1460–70.
Capehorn MS, Catarig AM, Furberg JK, Janez A, Price HC, Tadayon S, et al. Efficacy and safety of once-weekly semaglutide 1.0 mg vs once-daily liraglutide 1.2 mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes Metab. 2020; 46: 100–9.
Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, et al. 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. JAMA. 2022; 327: 534–45.
Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, 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). Lancet. 2009; 374: 39
Buse JB, Nauck M, Forst T, Sheu WHH, Shenouda SK, Heilmann CR, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet. 2013; 381: 117–24.
Buse JB, Drucker DJ, Taylor KL, Kim T, Walsh B, Hu H, et al. DURATION-1: Exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010; 33: 1255–61.
Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017; 19: 1242–51.
Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AYM, et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: A randomized, controlled trial. Ann Intern Med. 2011; 154: 103-12. doi: 10.7326/0003-4819-154-2-201101180-00300.2011.
Bolli GB, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Wu Y, et al. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). Diabet Med. 2014; 31: 176–84.
Basolo A, Burkholder J, Osgood K, Graham A, Bundrick S, Frankl J, et al. Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial. Metabolism. 2018; 85: 116-25.
Blonde L, Belousova L, Fainberg U, Garcia-Hernandez PA, Jain SM, Kaltoft MS, et al. Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2020; 22: 929-37.
Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, et al. Effects of liraglutide in the treatment of obesity: A randomised, double-blind, placebo-controlled study. Lancet 2009; 374: 1606-16. doi: 10.1016/S0140-6736(09)61375-1.
Arslanian SA, Hannon T, Zeitler P, Chao LC, Boucher-Berry C, Barrientos-Pérez M, et al. Once-weekly dulaglutide for the treatment of youths with type 2 diabetes. N Engl J Med. 2022; 387: 433-43.
Ariel D, Kim SH, Abbasi F, Lamendola CA, Liu A, Reaven GM. Effect of liraglutide administration and a calorie-restricted diet on lipoprotein profile in overweight/obese persons with prediabetes. Nutr Metab Cardiovasc Dis. 2014; 24: 1317-22.
Aroda VR, Rosenstock J, Terauchi Y, Altuntas Y, Lalic NM, Villegas ECM, et al. PIONEER 1: Randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care. 2019; 42: 1724-32.
Apovian CM, Bergenstal RM, Cuddihy RM, Qu Y, Lenox S, Lewis MS, et al. Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med. 2010; 123:468.e9-17. doi: 10.1016/j.amjmed.2009.11.019.
Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-week, open-label, randomized clinical trial. Diabetes Care 2018; 41: 258-66.
Ahrén B, Vorokhobina N, Souhami E, Demil N, Ye J, Aronson R. Equal improvement in glycaemia with lixisenatide given before breakfast or the main meal of the day. J Diabetes Complications. 2014; 28: 735-41.
Ahrén B, Dimas AL, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). Diabetes Care. 2013; 36: 2543-50.
Ahmann A, Rodbard HW, Rosenstock J, Lahtela JT, de Loredo L, Tornøe K, et al. Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: A randomized, placebo-controlled trial. Diabetes Obes Metab. 2015; 17: 1056-64.
Siriyotha S, Anothaisintawee T, Looareesuwan P, Nimitphong H, McKay GJ, Attia J, et al. Effectiveness of glucagon-like peptide-1 receptor agonists for reduction of body mass index and blood glucose control in patients with type 2 diabetes mellitus and obesity: A retrospective cohort study and difference-in-difference analysis. BMJ Open. 2024; 14: e086424.
Yao H, Zhang A, Li D, Wu Y, Wang CZ, Wan JY, et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: Systematic review and network meta-analysis. BMJ 2024:384: e076410. doi: 10.1136/bmj-2023-076410.
Sun F, Wu S, Guo S, Yu K, Yang Z, Li L, et al. Effect of GLP-1 receptor agonists on waist circumference among type 2 diabetes patients: A systematic review and network meta-analysis. Endocrine. 2015; 48: 794-803.
Egbe AC, Miranda WR, Anderson JH, Connolly HM. Prognostic implications of weight gain and weight loss in adults with congenital heart disease. Int J Cardiol. 2023; 371: 147-52.
Fan H, Li X, Zheng L, Chen X, Lan Q, Wu H, et al. Abdominal obesity is strongly associated with cardiovascular disease and its risk factors in elderly and very elderly community-dwelling Chinese. Sci Rep. 2016; 6: 21521. doi: 10.1038/srep21521
