J Korean Diabetes.  2018 Mar;19(1):35-40. 10.4093/jkd.2018.19.1.35.

Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association

• Kim HJ

• KMID: 2408656
• DOI: http://doi.org/10.4093/jkd.2018.19.1.35

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were recommended as a monotherapy or combination therapy with oral hypoglycemic agents or basal insulin in the position statement of the Korean Diabetes Association 2017 for pharmacological therapy, which was a change from the previous guideline that recommended them only as a combination therapy. Many randomized clinical trials and systematic reviews report that GLP-1RAs have considerable glucose-lowering effect and lead to weight reduction and low risk of hypoglycemia when used as a monotherapy or combination therapy. The results of cardiovascular outcome trials of long-acting GLP-1RAs (liraglutide, semaglutide) have demonstrated cardiovascular benefits in subjects with type 2 diabetes mellitus and a high risk of cardiovascular disease. The GLP-1RAs may be a choice of therapy when weight control and avoidance of hypoglycemia are important, and patients with high risk of cardiovascular disease might also favor choosing GLP-1RA.

Keyword

Cardiovascular diseases; Diabetes mellitus; Glucagon-like peptide-1 receptor agonist; Hypoglycemia; Obesity; Practice guideline

MeSH Terms

Cardiovascular Diseases
Diabetes Mellitus
Diabetes Mellitus, Type 2*
Glucagon-Like Peptide 1*
Glucagon-Like Peptide-1 Receptor*
Humans
Hypoglycemia
Hypoglycemic Agents
Insulin
Obesity
Weight Loss
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents
Insulin

Reference

1. Ko SH, Hur KY, Rhee SY, Kim NH, Moon MK, Park SO, Lee BW, Kim HJ, Choi KM, Kim JH;. Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association. Diabetes Metab J. 2017; 41:337–348.

2. Kim HJ, Park SO, Ko SH, Rhee SY, Hur KY, Kim NH, Moon MK, Lee BW, Kim JH, Choi KM. Committee of Clinical Practice Guidelines of the Korean Diabetes Association. Glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes mellitus: a position statement of the Korean Diabetes Association. Diabetes Metab J. 2017; 41:423–429.

3. Nauck MA, Meier JJ, Cavender MA, Abd El, Drucker DJ. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation. 2017; 136:849–870.

4. Thrasher J. Pharmacologic management of type 2 diabetes mellitus: available therapies. Am J Med. 2017; 130(6S):S4–17.

5. Madsbad S. Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists. Diabetes Obes Metab. 2016; 18:317–332.

6. Monami M, Dicembrini I, Marchionni N, Rotella CM, Mannucci E. Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis. Exp Diabetes Res. 2012; 2012:672658.

7. Domecq JP, Prutsky G, Leppin A, Sonbol MB, Altayar O, Undavalli C, Wang Z, Elraiyah T, Brito JP, Mauck KF, Lababidi MH, Prokop LJ, Asi N, Wei J, Fidahussein S, Montori VM, Murad MH. Clinical review: drugs commonly associated with weight change: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2015; 100:363–370.

8. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJ, Probstfield JL, Riddle MC, Solomon SD, Tardif JC;. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015; 373:2247–2257.

9. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, Nissen SE, Pocock S, Poulter NR, Ravn LS, Steinberg WM, Stockner M, Zinman B, Bergenstal RM, Buse JB. LEADER Steering Committee. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375:311–322.

10. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T;. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375:1834–1844.

11. Garber A, Henry RR, Ratner R, Hale P, Chang CT, Bode B. LEAD-3 (Mono) Study Group. Liraglutide, a oncedaily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab. 2011; 13:348–356.

12. Umpierrez G, Tofé Povedano S, Pérez Manghi F, Shurzinske L, Pechtner V. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care. 2014; 37:2168–2176.

13. Cimmaruta D, Maiorino MI, Scavone C, Sportiello L, Rossi F, Giugliano D, Esposito K, Capuano A. Efficacy and safety of insulin-GLP-1 receptor agonists combination in type 2 diabetes mellitus: a systematic review. Expert Opin Drug Saf. 2016; 15:Suppl 2. 77–83.

14. Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH. 4B Study Group. Glucagonlike peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37:2763–2773.

15. Yoon KH, Hardy E, Han J. Exenatide versus insulin lispro added to basal insulin in a subgroup of Korean patients with type 2 diabetes mellitus. Diabetes Metab J. 2017; 41:69–74.

16. Mathieu C, Rodbard HW, Cariou B, Handelsman Y, Philis-Tsimikas A, Ocampo Francisco AM, Rana A, Zinman B. BEGIN: VICTOZA ADD-ON (NN1250-3948) study group. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab. 2014; 16:636–644.

17. Pozzilli P, Norwood P, Jódar E, Davies MJ, Ivanyi T, Jiang H, Woodward DB, Milicevic Z. Placebo-controlled, randomized trial of the addition of once-weekly glucagonlike peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (AWARD-9). Diabetes Obes Metab. 2017; 19:1024–1031.

18. Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simó R. Liraglutide Effect and Action in Diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia. 2009; 52:2046–2055.

19. Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L;. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes (LEAD-4 Met+TZD). Diabetes Care. 2009; 32:1224–1230.

20. 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.

21. Nauck M, Weinstock RS, Umpierrez GE, Guerci B, Skrivanek Z, Milicevic Z. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care. 2014; 37:2149–2158.

22. Abd El, Kahle M, Meier JJ, Nauck MA. A metaanalysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients. Diabetes Obes Metab. 2017; 19:216–227.