Diabetes Metab J.  2015 Jun;39(3):177-187. 10.4093/dmj.2015.39.3.177.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea

• Oh S
• Chon S
• Ahn KJ
• Jeong IK
• Kim BJ
• Kang JG

• KMID: 2281530
• DOI: http://doi.org/10.4093/dmj.2015.39.3.177

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Keyword

Clinical management; Diabetes mellitus, type 2; Glucagon-like peptide-1 receptor agonists; Glycemic control; Hyperglycemia; Postprandial period

MeSH Terms

Appetite
Asian Continental Ancestry Group
Body Mass Index
Compliance
Diabetes Mellitus, Type 2
Glucagon-Like Peptide 1*
Glucose
Hemoglobin A, Glycosylated
Humans
Hyperglycemia
Hypoglycemia
Korea
Obesity
Overweight
Postprandial Period
Prevalence
Weight Loss
Glucagon-Like Peptide-1 Receptor
Glucagon-Like Peptide 1
Glucose

Reference

1. Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009; 301:2129–2140.

2. Hu FB. Globalization of diabetes: the role of diet, lifestyle, and genes. Diabetes Care. 2011; 34:1249–1257.

3. Kim SM, Lee JS, Lee J, Na JK, Han JH, Yoon DK, Baik SH, Choi DS, Choi KM. Prevalence of diabetes and impaired fasting glucose in Korea: Korean National Health and Nutrition Survey 2001. Diabetes Care. 2006; 29:226–231.

4. Koo BK, Kim EK, Choi H, Park KS, Moon MK. Decreasing trends of the prevalence of diabetes and obesity in Korean women aged 30-59 years over the past decade: results from the Korean National Health and Nutrition Examination Survey, 2001-2010. Diabetes Care. 2013; 36:e95–e96.

5. Kim CS, Ko SH, Kwon HS, Kim NH, Kim JH, Lim S, Choi SH, Song KH, Won JC, Kim DJ, Cha BY. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association. Prevalence, awareness, and management of obesity in Korea: data from the Korea national health and nutrition examination survey (1998-2011). Diabetes Metab J. 2014; 38:35–43.

6. Koo BK, Lee CH, Yang BR, Hwang SS, Choi NK. The incidence and prevalence of diabetes mellitus and related atherosclerotic complications in Korea: a National Health Insurance Database Study. PLoS One. 2014; 9:e110650.

7. Ko SH, Kim SR, Kim DJ, Oh SJ, Lee HJ, Shim KH, Woo MH, Kim JY, Kim NH, Kim JT, Kim CH, Kim HJ, Jeong IK, Hong EK, Cho JH, Mok JO, Yoon KH. Committee of Clinical Practice Guidelines, Korean Diabetes Association. 2011 Clinical practice guidelines for type 2 diabetes in Korea. Diabetes Metab J. 2011; 35:431–436.

8. Holst JJ, Vilsboll T. Combining GLP-1 receptor agonists with insulin: therapeutic rationales and clinical findings. Diabetes Obes Metab. 2013; 15:3–14.

9. Werner U. Effects of the GLP-1 receptor agonist lixisenatide on postprandial glucose and gastric emptying: preclinical evidence. J Diabetes Complications. 2014; 28:110–114.

10. Phillips LK, Prins JB. Update on incretin hormones. Ann N Y Acad Sci. 2011; 1243:E55–E74.

11. Wong MC, Wang HH, Kwan MW, Zhang DD, Liu KQ, Chan SW, Fan CK, Fong BC, Li ST, Griffiths SM. Comparative effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors and human glucagon-like peptide-1 (GLP-1) analogue as add-on therapies to sulphonylurea among diabetes patients in the Asia-Pacific region: a systematic review. PLoS One. 2014; 9:e90963.

12. Shyangdan DS, Royle P, Clar C, Sharma P, Waugh N, Snaith A. Glucagon-like peptide analogues for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2011; (10):CD006423.

13. 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.

14. Fineman MS, Cirincione BB, Maggs D, Diamant M. GLP-1 based therapies: differential effects on fasting and postprandial glucose. Diabetes Obes Metab. 2012; 14:675–688.

15. Lorber D. GLP-1 receptor agonists: effects on cardiovascular risk reduction. Cardiovasc Ther. 2013; 31:238–249.

16. Ratner R, Han J, Nicewarner D, Yushmanova I, Hoogwerf BJ, Shen L. Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes. Cardiovasc Diabetol. 2011; 10:22.

17. Marso SP, Lindsey JB, Stolker JM, House JA, Martinez Ravn G, Kennedy KF, Jensen TM, Buse JB. Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2: 3 liraglutide clinical development studies. Diab Vasc Dis Res. 2011; 8:237–240.

18. Morano S, Romagnoli E, Filardi T, Nieddu L, Mandosi E, Fallarino M, Turinese I, Dagostino MP, Lenzi A, Carnevale V. Short-term effects of glucagon-like peptide 1 (GLP-1) receptor agonists on fat distribution in patients with type 2 diabetes mellitus: an ultrasonography study. Acta Diabetol. 2015; 01. 1. [Epub]. DOI: 10.1007/s00592-014-0710-z.

19. Marso SP, Poulter NR, Nissen SE, Nauck MA, Zinman B, Daniels GH, Pocock S, Steinberg WM, Bergenstal RM, Mann JF, Ravn LS, Frandsen KB, Moses AC, Buse JB. Design of the liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013; 166:823–830.

20. Gerich J. Pathogenesis and management of postprandial hyperglycemia: role of incretin-based therapies. Int J Gen Med. 2013; 6:877–895.

21. Ceriello A, Colagiuri S. International Diabetes Federation guideline for management of postmeal glucose: a review of recommendations. Diabet Med. 2008; 25:1151–1156.

22. Rodbard HW, Blonde L, Braithwaite SS, Brett EM, Cobin RH, Handelsman Y, Hellman R, Jellinger PS, Jovanovic LG, Levy P, Mechanick JI, Zangeneh F. AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Endocr Pract. 2007; 13:Suppl 1. 1–68.

23. American Diabetes Association. Standards of medical care in diabetes: 2011. Diabetes Care. 2011; 34:Suppl 1. S11–S61.

24. DECODA Study Group. International Diabetes Epidemiology Group. Cardiovascular risk profile assessment in glucose-intolerant Asian individuals: an evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Asia). Diabet Med. 2002; 19:549–557.

25. DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. BMJ. 1998; 317:371–375.

26. Suh S, Joung JY, Jin SM, Kim MY, Bae JC, Park HD, Lee MS, Lee MK, Kim JH. Strong correlation between glycaemic variability and total glucose exposure in type 2 diabetes is limited to subjects with satisfactory glycaemic control. Diabetes Metab. 2014; 40:272–277.

27. Haimoto H, Sasakabe T, Umegaki H, Wakai K. Acute metabolic responses to a high-carbohydrate meal in outpatients with type 2 diabetes treated with a low-carbohydrate diet: a crossover meal tolerance study. Nutr Metab (Lond). 2009; 6:52.

28. Kim MK, Suk JH, Kwon MJ, Chung HS, Yoon CS, Jun HJ, Ko JH, Kim TK, Lee SH, Oh MK, Rhee BD, Park JH. Nateglinide and acarbose for postprandial glucose control after optimizing fasting glucose with insulin glargine in patients with type 2 diabetes. Diabetes Res Clin Pract. 2011; 92:322–328.

29. Kim YG, Hahn S, Oh TJ, Kwak SH, Park KS, Cho YM. Differences in the glucose-lowering efficacy of dipeptidyl peptidase-4 inhibitors between Asians and non-Asians: a systematic review and meta-analysis. Diabetologia. 2013; 56:696–708.

30. Seino Y, Min KW, Niemoeller E, Takami A. EFC10887 GETGOAL-L Asia Study Investigators. 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; 14:910–917.

31. Becker RH, Stechl J, Msihid J, Kapitza C. Lixisenatide resensitizes the insulin-secretory response to intravenous glucose challenge in people with type 2 diabetes: a study in both people with type 2 diabetes and healthy subjects. Diabetes Obes Metab. 2014; 16:793–800.

32. Bolli GB, Owens DR. Lixisenatide, a novel GLP-1 receptor agonist: efficacy, safety and clinical implications for type 2 diabetes mellitus. Diabetes Obes Metab. 2014; 16:588–601.

33. Petersen AB, Christensen M. Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus. Diabetes Metab Syndr Obes. 2013; 6:217–231.

34. Owens DR, Monnier L, Bolli GB. Differential effects of GLP-1 receptor agonists on components of dysglycaemia in individuals with type 2 diabetes mellitus. Diabetes Metab. 2013; 39:485–496.

35. 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.

36. Lorenz M, Pfeiffer C, Steinstrasser A, Becker RH, Rutten H, Ruus P, Horowitz M. Effects of lixisenatide once daily on gastric emptying in type 2 diabetes: relationship to postprandial glycemia. Regul Pept. 2013; 185:1–8.

37. Scholz GH, Fleischmann H. Basal insulin combined incretin mimetic therapy with glucagon-like protein 1 receptor agonists as an upcoming option in the treatment of type 2 diabetes: a practical guide to decision making. Ther Adv Endocrinol Metab. 2014; 5:95–123.

38. Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D, Porter L. DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008; 372:1240–1250.

39. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. LEAD-6 Study Group. 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; 374:39–47.

40. Kapitza C, Forst T, Coester HV, Poitiers F, Ruus P, Hincelin-Mery A. Pharmacodynamic characteristics of lixisenatide once daily versus liraglutide once daily in patients with type 2 diabetes insufficiently controlled on metformin. Diabetes Obes Metab. 2013; 15:642–649.

41. Meier JJ, Rosenstock J, Hincelin-Mery A, Roy-Duval C, Delfolie A, Coester HV, Forst T, Kapitza C. Effect of lixisenatide vs liraglutide on glycemic control, gastric emptying, and safety parameters in optimized insulin glargine T2DM ± metformin. In : Proceedings of American Diabetes Association 74th Scientific Sessions; 2014 Jun 13-17; San Francisco, CA. Alexandria (VA): American Diabetes Association;2014.

42. Wysham C, Blevins T, Arakaki R, Colon G, Garcia P, Atisso C, Kuhstoss D, Lakshmanan M. 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; 37:2159–2167.

43. Kim YG, Hahn S, Oh TJ, Park KS, Cho YM. Differences in the HbA1c-lowering efficacy of glucagon-like peptide-1 analogues between Asians and non-Asians: a systematic review and meta-analysis. Diabetes Obes Metab. 2014; 16:900–909.

44. Kadowaki T, Namba M, Imaoka T, Yamamura A, Goto W, Boardman MK, Sowa H. 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; 2:210–217.

45. Kadowaki T, Namba M, Yamamura A, Sowa H, Wolka AM, Brodows RG. Exenatide exhibits dose-dependent effects on glycemic control over 12 weeks in Japanese patients with suboptimally controlled type 2 diabetes. Endocr J. 2009; 56:415–424.

46. Kaku K, Rasmussen MF, Clauson P, Seino Y. Improved glycaemic control with minimal hypoglycaemia and no weight change with the once-daily human glucagon-like peptide-1 analogue liraglutide as add-on to sulphonylurea in Japanese patients with type 2 diabetes. Diabetes Obes Metab. 2010; 12:341–347.

47. Gao Y, Yoon KH, Chuang LM, Mohan V, Ning G, Shah S, Jang HC, Wu TJ, Johns D, Northrup J, Brodows R. 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.

48. Yang W, Chen L, Ji Q, Liu X, Ma J, Tandon N, Bhattacharyya A, Kumar A, Kim KW, Yoon KH, Bech OM, Zychma M. Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*). Diabetes Obes Metab. 2011; 13:81–88.

49. Shin J, Chang JS, Kim HS, Ko SH, Cha BY, Son HY, Yoon KH, Cho JH. Effects of a 6-month exenatide therapy on HbA1c and weight in Korean patients with type 2 diabetes: a retrospective cohort study. Diabetes Metab J. 2012; 36:364–370.

50. Prately RE, Nauck MA, Barnett AH, Feinglos MN, Ovalle F, Harman-Boehm I, Ye J, Scott R, Johnson S, Stewart M, Rosenstock J. HARMONY 7 study group. Once-weekly albiglutide versus once-daily liraglutide in patients with type 2 diabetes inadequately controlled on oral drugs (HARMONY 7): a randomised, open-label, multicentre, non-inferiority phase 3 study. Lancet Diabetes Endocrinol. 2014; 2:289–297.

51. Yun JS, Ko SH. Avoiding or coping with severe hypoglycemia in patients with type 2 diabetes. Korean J Intern Med. 2015; 30:6–16.

52. Sun F, Yu K, Yang Z, Wu S, Zhang Y, Shi L, Ji L, Zhan S. Impact of GLP-1 receptor agonists on major gastrointestinal disorders for type 2 diabetes mellitus: a mixed treatment comparison meta-analysis. Exp Diabetes Res. 2012; 2012:230624.

53. Petersen AB, Knop FK, Christensen M. Lixisenatide for the treatment of type 2 diabetes. Drugs Today (Barc). 2013; 49:537–553.

54. Reid TS. Practical use of glucagon-like peptide-1 receptor agonist therapy in primary care. Clin Diabetes. 2013; 31:148–157.

55. Ratanawongsa N, Crosson JC, Schillinger D, Karter AJ, Saha CK, Marrero DG. Getting under the skin of clinical inertia in insulin initiation: the Translating Research Into Action for Diabetes (TRIAD) Insulin Starts Project. Diabetes Educ. 2012; 38:94–100.

56. Kalra S, Kalra B. Counselling patients for GLP-1 analogue therapy: comparing GLP-1 analogue with insulin counselling. N Am J Med Sci. 2012; 4:638–640.

57. Jung HS, Chang Y, Yun KE, Kim CW, Choi ES, Kwon MJ, Cho J, Zhang Y, Rampal S, Zhao D, Soo Kim H, Shin H, Guallar E, Ryu S. Impact of body mass index, metabolic health and weight change on incident diabetes in a Korean population. Obesity (Silver Spring). 2014; 22:1880–1887.