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Glucagon-like peptide analogues for type 2 diabetes mellitus : systematic review and meta-analysis

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Shyangdan, Deepson S., Royle, Pamela, Clar, C., Sharma, Pawana and Waugh, Norman. (2010) Glucagon-like peptide analogues for type 2 diabetes mellitus : systematic review and meta-analysis. BMC Endocrine Disorders, Vol.10 . p. 20. ISSN 1472-6823

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Official URL: http://dx.doi.org/10.1186/1472-6823-10-20

Abstract

Background Glucagon-like peptide (GLP-1) analogues are a new class of drugs used in the treatment of type 2 diabetes. They are given by injection, and regulate glucose levels by stimulating glucose-dependent insulin secretion and biosynthesis, suppressing glucagon secretion, and delaying gastric emptying and promoting satiety. This systematic review aims to provide evidence on the clinical effectiveness of the GLP-1 agonists in patients not achieving satisfactory glycaemic control with one or more oral glucose lowering drugs. Methods MEDLINE, EMBASE, the Cochrane Library and Web of Science were searched to find the relevant papers. We identified 28 randomised controlled trials comparing GLP-1 analogues with placebo, other glucose-lowering agents, or another GLP-1 analogue, in patients with type 2 diabetes with inadequate control on a single oral agent, or on dual therapy. Primary outcomes included HbA1c, weight change and adverse events. Results Studies were mostly of short duration, usually 26 weeks. All GLP-1 agonists reduced HbA1c by about 1% compared to placebo. Exenatide twice daily and insulin gave similar reductions in HbA1c, but exenatide 2 mg once weekly and liraglutide 1.8 mg daily reduced it by 0.20% and 0.30% respectively more than glargine. Liraglutide 1.2 mg daily reduced HbA1c by 0.34% more than sitagliptin 100 mg daily. Exenatide and liraglutide gave similar improvements in HbA1c to sulphonylureas. Exenatide 2 mg weekly and liraglutide 1.8 mg daily reduced HbA1c by more than exenatide 10 μg twice daily and sitagliptin 100 mg daily. Exenatide 2 mg weekly reduced HbA1c by 0.3% more than pioglitazone 45 mg daily. Exenatide and liraglutide resulted in greater weight loss (from 2.3 to 5.5 kg) than active comparators. This was not due simply to nausea. Hypoglycaemia was uncommon, except when combined with a sulphonylurea. The commonest adverse events with all GLP-1 agonists were initial nausea and vomiting. The GLP-1 agonists have some effect on beta-cell function, but this is not sustained after the drug is stopped. Conclusions GLP-1 agonists are effective in improving glycaemic control and promoting weight loss.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Health Sciences
Library of Congress Subject Headings (LCSH): Non-insulin-dependent diabetes -- Treatment, Glucagon-like peptide 1 -- Effectiveness
Journal or Publication Title: BMC Endocrine Disorders
Publisher: BioMed Central Ltd.
ISSN: 1472-6823
Date: December 2010
Volume: Vol.10
Page Range: p. 20
Identification Number: 10.1186/1472-6823-10-20
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
References: 1. Turner R, Cull C, Holman R: United Kingdom prospective diabetes study 17: A 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Annals of Internal Medicine 1996, 124:136-145. 2. Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR, UK Prospective Diabetes Study Grp: Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. British Medical Journal 2000, 321:405-412. 3. Type 2 diabetes: the management of type 2 diabetes. NICE clinical guideline 87. [http://www.nice.org.uk/cg87]. 4. UKPDS16: U.K. prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 1995, 44:1249-1258. 5. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B: Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009, 32:193-203. 6. Hayward RA, Manning WG, Kaplan SH, Wagner EH, Greenfield S: Starting insulin therapy in patients with type 2 diabetes - Effectiveness, complications, and resource utilization. Jama-Journal of the American Medical Association 1997, 278:1663-1669. 7. Baggio LL, Huang QL, Brown TJ, Drucker DJ: A recombinant human glucagon-like peptide (GLP)-1-albumin protein (Albugon) mimics peptidergic activation of GLP-1 receptor-dependent pathways coupled with satiety, gastrointestinal motility, and glucose homeostasis. Diabetes 2004, 53:2492-2500. 8. Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W: Normalization of Fasting Hyperglycemia by Exogenous Glucagon-Like Peptide-1 (7-36 Amide) in Type-2 (Non-Insulin-Dependent) Diabetic- Patients. Diabetologia 1993, 36:741-744. 9. Amori RE, Lau J, Pittas AG: Efficacy and safety of incretin therapy in type 2 diabetes - Systematic review and meta-analysis. Jama-Journal of the American Medical Association 2007, 298:194-206. 10. Barnett AH: New treatments in type 2 diabetes: a focus on the incretinbased therapies. Clinical Endocrinology 2009, 70:343-353. 11. Monami M, Marchionni N, Mannucci E: Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials. European Journal of Endocrinology 2009, 160:909-917. 12. Norris SL, Lee N, Thakurta S, Chan BKS: Exenatide efficacy and safety: a systematic review. Diabetic Medicine 2009, 26:837-846. 13. Xu G, Stoffers DA, Habener JF, Bonner-Weir S: Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes 1999, 48:2270-2276. 14. Farilla L, Bulotta A, Hirshberg B, Calzi SL, Khoury N, Noushmehr H, Bertolotto C, Di Mario U, Harlan DM, Perfetti R: Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets. Endocrinology 2003, 144:5149-5158. 15. Li YZ, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ: Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. Journal of Biological Chemistry 2003, 278:471-478. 16. Kobayashi M, Yamazaki K, Hirao K, Oishi M, Kanatsuka A, Yamauchi M, Takagi H, Kawai K: The status of diabetes control and antidiabetic drug therapy in Japan–a cross-sectional survey of 17,000 patients with diabetes mellitus (JDDM 1). Diabetes Res Clin Pract 2006, 73:198-204. 17. Neville SE, Boye KS, Montgomery WS, Iwamoto K, Okamura M, Hayes RP: Diabetes in Japan: a review of disease burden and approaches to treatment. Diabetes Metab Res Rev 2009, 25:705-716. 18. 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. 19. Higgins J, Altman DG: Assessing Risk of Bias in Included Studies. Cochrane Handbook for Systematic Reviews of Interventions 2008, 187-241. 20. 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. Endocrine Journal 2009, 56:415-424. 21. Kendall DM, Riddle MC, Rosenstock J, Zhuang DL, 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, 28:1083-1091. 22. DeFronzo RA, Triplitt C, Qu Y, Lewis MS, Maggs D, Glass LC: Effects Of Exenatide Plus Rosiglitazone On Beta Cell Function And Insulin Sensitivity In Subjects With Type 2 Diabetes On Metformin. Diabetes Care 2010. 23. Rosenstock J, Reusch J, Bush M, Yang F, Stewart M: Potential of albiglutide, a long-acting GLP-1 receptor agonist, in type 2 diabetes: a randomized controlled trial exploring weekly, biweekly, and monthly dosing. Diabetes Care 2009, 32:1880-1886. 24. Nauck MA, Ratner RE, Kapitza C, Berria R, Boldrin M, Balena R: Treatment with the human once-weekly glucagon-like peptide-1 analog taspoglutide in combination with metformin improves glycemic control and lowers body weight in patients with type 2 diabetes inadequately controlled with metformin alone: a double-blind placebo-controlled study. Diabetes Care 2009, 32:1237-1243. 25. Ratner R, Nauck M, Kapitza C, Asnaghi V, Boldrin M, Balena R: Safety and tolerability of high doses of taspoglutide, a once-weekly human GLP-1 analogue, in diabetic patients treated with metformin: a randomized double-blind placebo-controlled study. Diabet Med 2010, 27:556-562. 26. Gill A, Hoogwerf BJ, Burger J, Bruce S, MacConell L, Yan P, Braun D, Giaconia J, Malone J: Effect of exenatide on heart rate and blood pressure in subjects with type 2 diabetes mellitus: a double-blind, placebo-controlled, randomized pilot study. Cardiovasc Diabetol 2010, 9:6. 27. Derosa G, Maffioli P, Salvadeo SA, Ferrari I, Ragonesi PD, Querci F, Franzetti IG, Gadaleta G, Ciccarelli L, Piccinni MN, et al: Exenatide versus glibenclamide in patients with diabetes. Diabetes Technol Ther 2010, 12:233-240. 28. Bergenstal R, Lewin A, Bailey T, Chang D, Gylvin T, Roberts V, NovoLog Mixvs- Exenatide Study Grp: Efficacy and safety of biphasic insulin aspart 70/ 30 versus exenatide in subjects with type 2 diabetes failing to achieve glycemic control with metformin and a sulfonylurea. Current Medical Research and Opinion 2009, 25:65-75. 29. 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. 30. Davies MJ, Donnelly R, Barnett AH, Jones S, Nicolay C, Kilcoyne A: Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study. Diabetes Obesity & Metabolism 2009, 11:1153-1162. 31. Davis SN, Johns D, Maggs D, Xu H, Northrup JH, Brodows RG: Exploring the substitution of exenatide for insulin in patients with type 2 diabetes treated with insulin in combination with oral antidiabetes agents. Diabetes Care 2007, 30:2767-2772. 32. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG, Gwaa SG: Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes - A randomized trial. Annals of Internal Medicine 2005, 143:559-569. 33. Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A, Brodows R, Trautmann M: A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 2007, 50:259-267. 34. Diamant M, Van GL, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M: Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010, 375:2234-2243. 35. Russell-Jones D, Vaag A, Schmitz O, Sethi BK, Lalic N, Antic S, Zdravkovic M, Ravn GM, Simo R, Liraglutide Effect AD: 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. 36. Nauck M, Frid A, Hermansen K, Shah NS, Tankova T, Mitha IH, Zdravkovic M, During M, Matthews DR, Study G: Efficacy and Safety Comparison of Liraglutide, Glimepiride, and Placebo, All in Combination With Metformin, in Type 2 Diabetes The LEAD (Liraglutide Effect and Action in Diabetes)-2 study. Diabetes Care 2009, 32:84-90. 37. Bergenstal RM, Wysham C, MacConell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE: Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet 2010. 38. Pratley RE, Nauck M, Bailey T, Montanya E, Cuddihy R, Filetti S, Thomsen AB, Sondergaard RE, Davies M: Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial. Lancet 2010, 375:1447-1456. 39. Marre M, Shaw J, Brandle M, Bebakar WMW, Kamaruddin NA, Strand J, Zdravkovic M, Le Thi TD, Colagiuri S, Su SG: Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabetic Medicine 2009, 26:268-278. 40. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L, Study G: 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. 41. Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang DL, Porter L, Study G: 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. 42. 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, 28:1092-1100. 43. Apovian CM, Bergenstal RM, Cuddihy RM, Qu Y, Lenox S, Lewis MS, Glass LC: Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. Am J Med 2010, 123:468-17. 44. Zinman B, Gerich J, Buse JB, Lewin A, Schwartz S, Raskin P, Hale PM, Zdravkovic M, Blonde L, Study I: 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. 45. Gao Y, Yoon KH, Chuang LM, Mohan V, Ning G, Shah S, Jang HC, Wu TJ, Johns D, Northrup J, 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 Research and Clinical Practice 2009, 83:69-76. 46. Kendall D, Nielsen L, Han J, Brodows R, Bhole D: Metabolic improvement associated with temporal pattern of weight loss in exenatide-treated patients with type 2 diabetes. Diabetologia 2008, 51:886. 47. Loh J, Clement SC: Efficacy of exenatide therapy over two years in a “Real World” setting. Diabetes 2008, 57:A32. 48. Guideline for managment of postmeal glucose. [http://www.idf.org/ webdata/docs/Guideline_PMG_final.pdf]. 49. Guide to the methods of technology appraisal. [http://www.nice.org.uk/ aboutnice/howwework/devnicetech/technologyappraisalprocessguides/ guidetothemethodsoftechnologyappraisal.jsp]. 50. Waugh N, Cummins E, Royle P, Clar C, Marien M, Richter B, Philip S: Newer agents for blood glucose control in type 2 diabetes: systematic review and economic evaluation. Health Technology Assessment 2010. 51. Sheffield CA, Kane MP, Busch RS, Bakst G, Abelseth JM, Hamilton RA: Safety and efficacy of exenatide in combination with insulin in patients with type 2 diabetes mellitus. Endocr Pract 2008, 14:285-292. 52. Information for Healthcare Professionals: Exenatide (marketed as Byetta). [http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ucm124713.htm]. 53. Byetta Safety Update for Healthcare Professionals. [http://www.fda.gov/ Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm190406.htm]. 54. Information for Healthcare Professionals: Reports of Altered Kidney Function in patients using Exenatide (Marketed as Byetta). [http://www. fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm188656.htm]. 55. Assessment report for Victoza (liraglutide). [http://www.ema.europa.eu/ ema/index.jsp?curl=pages/medicines/human/medicines/001026/ human_med_001137.jsp&murl=menus/medicines/medicines. jsp&mid=WC0b01ac058001d125#]. 56. Butler PC, Matveyenko AV, Dry S, Bhushan A, Elashoff R: Glucagon-like peptide-1 therapy and the exocrine pancreas: innocent bystander or friendly fire? Diabetologia 2010, 53:1-6. 57. Schernthaner G, Barnett AH, Betteridge DJ, Carmena R, Ceriello A, Charbonnel B, Hanefeld M, Lehmann R, Malecki MT, Nesto R, et al: Is the ADA/EASD algorithm for the management of type 2 diabetes (January 2009) based on evidence or opinion? A critical analysis. Diabetologia 2010, 53:1258-1269. 58. Fewtrell MS, Kennedy K, Singhal A, Martin RM, Ness A, Hadders-Algra M, Koletzko B, Lucas A: How much loss to follow-up is acceptable in longterm randomised trials and prospective studies? Arch Dis Child 2008, 93:458-461. 59. Schulz KF, Grimes DA: Sample size slippages in randomised trials: exclusions and the lost and wayward. Lancet 2002, 359:781-785. 60. Fonseca V, Rosenstock J, Patwardhan R, Salzman A: Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA 2000, 283:1695-1702. 61. Bunck MC, Corner A, Eliasson B, Heine RJ, Shaginian RM, Taskinen MR, Smith U, Yki-Jarvinen H, Diamant M: Three-Year Exenatide Therapy, Followed by a 4-Week Off-Drug Period, Had a Sustainable Effect on ß- Cell Disposition Index in Metformin Treated Patients with Type 2 Diabetes. 70th Scientific Session of the American Diabetes Association, June 25 - 29, Orlando, Florida 2010. 62. Vilsboll T: The effects of glucagon-like peptide-1 on the beta cell. Diabetes, Obesity & Metabolism 2009, 11(Suppl-8). 63. Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire JL, Keenan JF, Paul SK: Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009, 361:1736-1747. 64. Diabetes - liraglutide: appraisal consultation 2 document. [http://www. nice.org.uk/guidance/index.jsp?action=article&o=49173]. 65. Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Wintle ME, Maggs DG: Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008, 24:275-286. 66. Yki-Jarvinen H, Ryysy L, Nikkila K, Tulokas T, Vanamo R, Heikkila M: Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med 1999, 130:389-396. 67. Zinman B, Hoogwerf BJ, Garcia SD, Milton DR, Giaconia JM, Kim DD, Trautmann ME, Brodows RG: The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes - A randomized trial. Annals of Internal Medicine 2007, 146:477-485.
URI: http://wrap.warwick.ac.uk/id/eprint/37311

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