International Journal of Endocrinology and Metabolism

Published by: Kowsar

Insulin Monotherapy Versus Insulin Combined with Other Glucose-Lowering Agents in Type 2 Diabetes: A Narrative Review

Hengameh Abdi 1 , Fereidoun Azizi 1 , * and Atieh Amouzegar 1
Authors Information
1 Endocrine Research Centre, Research Institute for Endocrine Science, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
Article information
  • International Journal of Endocrinology and Metabolism: April 2018, 16 (2); e65600
  • Published Online: April 21, 2018
  • Article Type: Review Article
  • Received: December 27, 2017
  • Revised: April 4, 2018
  • Accepted: April 4, 2018
  • DOI: 10.5812/ijem.65600

To Cite: Abdi H, Azizi F, Amouzegar A. Insulin Monotherapy Versus Insulin Combined with Other Glucose-Lowering Agents in Type 2 Diabetes: A Narrative Review, Int J Endocrinol Metab. 2018 ;16(2):e65600. doi: 10.5812/ijem.65600.

Abstract
Copyright © 2018, International Journal of Endocrinology and Metabolism. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Context
2. Evidence Acquisition
3. Results
4. Conclusions
Acknowledgements
Footnotes
References
  • 1. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011;378(9786):169-81. doi: 10.1016/S0140-6736(11)60614-4. [PubMed: 21705072].
  • 2. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140-9. doi: 10.2337/dc14-2441. [PubMed: 25538310].
  • 3. Nakar S, Yitzhaki G, Rosenberg R, Vinker S. Transition to insulin in Type 2 diabetes: family physicians' misconception of patients' fears contributes to existing barriers. J Diabetes Complications. 2007;21(4):220-6. doi: 10.1016/j.jdiacomp.2006.02.004. [PubMed: 17616351].
  • 4. Rodriguez-Gutierrez R, Montori VM. Glycemic Control for Patients With Type 2 Diabetes Mellitus: Our Evolving Faith in the Face of Evidence. Circ Cardiovasc Qual Outcomes. 2016;9(5):504-12. doi: 10.1161/CIRCOUTCOMES.116.002901. [PubMed: 27553599].
  • 5. Goudswaard AN, Furlong NJ, Rutten GE, Stolk RP, Valk GD. Insulin monotherapy versus combinations of insulin with oral hypoglycaemic agents in patients with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2004;(4). CD003418. doi: 10.1002/14651858.CD003418.pub2. [PubMed: 15495054].
  • 6. Vos RC, van Avendonk MJ, Jansen H, Goudswaard AN, van den Donk M, Gorter K, et al. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. Cochrane Database Syst Rev. 2016;9. CD006992. doi: 10.1002/14651858.CD006992.pub2. [PubMed: 27640062].
  • 7. Holman RR, Steemson J, Turner RC. Sulphonylurea failure in type 2 diabetes: treatment with a basal insulin supplement. Diabet Med. 1987;4(5):457-62. [PubMed: 2959438].
  • 8. Lundershausen R, Orban S, Pissarek D, Panzram G. [Long-term effect of combination glibenclamide-insulin treatment in the secondary failure of sulfonylurea therapy--results of a one-year double blind study]. Wien Klin Wochenschr. 1987;99(17):603-8. [PubMed: 3118579].
  • 9. Pontiroli AE, Dino G, Capra F, Pozza G. Combined therapy with glibenclamide and ultralente insulin in lean patients with NIDDM with secondary failure of sulfonylureas. Follow up at two years. Diabete Metab. 1990;16(4):323-7. [PubMed: 2125014].
  • 10. Riddle MC, Hart JS, Bouma DJ, Phillipson BE, Youker G. Efficacy of bedtime NPH insulin with daytime sulfonylurea for subpopulation of type II diabetic subjects. Diabetes Care. 1989;12(9):623-9. [PubMed: 2507265].
  • 11. Riddle M, Hart J, Bingham P, Garrison C, McDaniel P. Combined therapy for obese type 2 diabetes: suppertime mixed insulin with daytime sulfonylurea. Am J Med Sci. 1992;303(3):151-6. [PubMed: 1595776].
  • 12. Riddle MC, Schneider J. Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group. Diabetes Care. 1998;21(7):1052-7. [PubMed: 9653594].
  • 13. Shank ML, Del Prato S, DeFronzo RA. Bedtime insulin/daytime glipizide. Effective therapy for sulfonylurea failures in NIDDM. Diabetes. 1995;44(2):165-72. [PubMed: 7859936].
  • 14. Sun Y, Xiong Y, Yang J. The effectiveness of combined insulin and sulfonylurea in treating non-insulin dependent diabetic patients. Zhonghua Nei Ke Za Zhi. 1995;34(4):246-9. [PubMed: 7587604].
  • 15. Bachmann W, Lotz N, Mehnert H, Rosak C, Schoffling K. Effectiveness of combined treatment with glibenclamide and insulin in secondary sulfonylurea failure. A controlled multicenter double-blind clinical trial. Dtsch Med Wochenschr. 1988;113(16):631-6. doi: 10.1055/s-2008-1067696. [PubMed: 3129273].
  • 16. Chow CC, Tsang LW, Sorensen JP, Cockram CS. Comparison of insulin with or without continuation of oral hypoglycemic agents in the treatment of secondary failure in NIDDM patients. Diabetes Care. 1995;18(3):307-14. [PubMed: 7555472].
  • 17. Fovenyi J, Grosz A, Thaisz E. Daytime sulfonyluyrea—bedtime insulin combination therapy in type 2 diabetes. Hungarian Arch Intern Med. 1997;50:607-13.
  • 18. Gutniak M, Karlander SG, Efendic S. Glyburide decreases insulin requirement, increases beta-cell response to mixed meal, and does not affect insulin sensitivity: effects of short- and long-term combined treatment in secondary failure to sulfonylurea. Diabetes Care. 1987;10(5):545-54. [PubMed: 2890501].
  • 19. Lotz N, Bachmann W, Ladik T, Mehnert H. Combination therapy with insulin/sulfonylurea in the long-term therapy of type II diabetes following "secondary failure". Klin Wochenschr. 1988;66(21):1079-84. [PubMed: 3148787].
  • 20. Ravnik-Oblak M, Mrevlje F. Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure. Diabetes Res Clin Pract. 1995;30(1):27-35. [PubMed: 8745203].
  • 21. Wolffenbuttel BH, Rondas-Colbers GJ, Menheere PP, Sels JP, Nieuwenhuijzen Kruseman AC. The effects of insulin combined with glibenclamide on glucose and lipid metabolism in patients with Type II diabetes mellitus. Ned Tijdschr Geneeskd. 1991;135(24):1080-4. [PubMed: 1906584].
  • 22. Wolffenbuttel BH, Sels JP, Rondas-Colbers GJ, Menheere PP, Nieuwenhuijzen Kruseman AC. Comparison of different insulin regimens in elderly patients with NIDDM. Diabetes Care. 1996;19(12):1326-32. [PubMed: 8941458].
  • 23. Yki-Jarvinen H, Kauppila M, Kujansuu E, Lahti J, Marjanen T, Niskanen L, et al. Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1992;327(20):1426-33. doi: 10.1056/NEJM199211123272005. [PubMed: 1406860].
  • 24. 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(5):389-96. [PubMed: 10068412].
  • 25. Bastyr EJ 3rd, Johnson ME, Trautmann ME, Anderson JH jr, Vignati L. Insulin lispro in the treatment of patients with type 2 diabetes mellitus after oral agent failure. Clin Ther. 1999;21(10):1703-14. [PubMed: 10566566].
  • 26. Casner PR. Insulin-glyburide combination therapy for non-insulin-dependent diabetes mellitus: A long-term double-blind, placebo-controlled trial. Clin Pharmacol Ther. 1988;44(5):594-603. doi: 10.1038/clpt.1988.199.
  • 27. Feinglos MN, Thacker CR, Lobaugh B, DeAtkine DD, McNeill DB, English JS, et al. Combination insulin and sulfonylurea therapy in insulin-requiring type 2 diabetes mellitus. Diabetes Res Clin Pract. 1998;39(3):193-9. [PubMed: 9649951].
  • 28. Mauerhoff T, Ketelslegers JM, Lambert AE. Effect of glibenclamide in insulin-treated diabetic patients with a residual insulin secretion. Diabete Metab. 1986;12(1):34-8. [PubMed: 3084315].
  • 29. Reich A, Abraira C, Lawrence AM. Combined glyburide and insulin therapy in type II diabetes. Diabetes Res. 1987;6(2):99-104. [PubMed: 3123116].
  • 30. Schade DS, Mitchell WJ, Griego G. Addition of sulfonylurea to insulin treatment in poorly controlled type II diabetes. A double-blind, randomized clinical trial. JAMA. 1987;257(18):2441-5. [PubMed: 3106656].
  • 31. Schiel R, Muller UA. Efficacy and treatment satisfaction of once-daily insulin glargine plus one or two oral antidiabetic agents versus continuing premixed human insulin in patients with type 2 diabetes previously on long-term conventional insulin therapy: the Switch pilot study. Exp Clin Endocrinol Diabetes. 2007;115(10):627-33. doi: 10.1055/s-2007-984445. [PubMed: 18058596].
  • 32. Simpson HC, Sturley R, Stirling CA, Reckless JP. Combination of insulin with glipizide increases peripheral glucose disposal in secondary failure type 2 diabetic patients. Diabet Med. 1990;7(2):143-7. [PubMed: 2137755].
  • 33. Stenman S, Groop PH, Saloranta C, Totterman KJ, Fyhrqvist F, Groop L. Effects of the combination of insulin and glibenclamide in type 2 (non-insulin-dependent) diabetic patients with secondary failure to oral hypoglycaemic agents. Diabetologia. 1988;31(4):206-13. [PubMed: 3133266].
  • 34. Kyllastinen M, Groop L. Combination of insulin and glibenclamide in the treatment of elderly non-insulin dependent (type 2) diabetic patients. Ann Clin Res. 1985;17(3):100-4. [PubMed: 3931537].
  • 35. Lindstrom T, Nystrom FH, Olsson AG, Ottosson AM, Arnqvist HJ. The lipoprotein profile differs during insulin treatment alone and combination therapy with insulin and sulphonylureas in patients with Type 2 diabetes mellitus. Diabet Med. 1999;16(10):820-6. [PubMed: 10547208].
  • 36. Kitabchi AE, Soria AG, Radparvar A, Lawson-Grant V. Combined therapy of insulin and tolazamide decreases insulin requirement and serum triglycerides in obese patients with noninsulin-dependent diabetes mellitus. Am J Med Sci. 1987;294(1):10-4. [PubMed: 3605188].
  • 37. Longnecker MP, Elsenhans VD, Leiman SM, Owen OE, Boden G. Insulin and a sulfonylurea agent in non-insulin-dependent diabetes mellitus. Arch Intern Med. 1986;146(4):673-6. [PubMed: 3516096].
  • 38. Quatraro A, Consoli G, Ceriello A, Giugliano D. Combined insulin and sulfonylurea therapy in non-insulin-dependent diabetics with secondary failure to oral drugs: a one year follow-up. Diabete Metab. 1986;12(6):315-8. [PubMed: 3545931].
  • 39. Groop L, Harno K, Nikkila EA, Pelkonen R, Tolppanen EM. Transient effect of the combination of insulin and sulfonylurea (glibenclamide) on glycemic control in non-insulin dependent diabetics poorly controlled with insulin alone. Acta Med Scand. 1985;217(1):33-9. [PubMed: 3919531].
  • 40. Osei K, O'Dorisio TM, Falko JM. Concomitant insulin and sulfonylurea therapy in patients with type II diabetes. Effects on glucoregulation and lipid metabolism. Am J Med. 1984;77(6):1002-9. [PubMed: 6439036].
  • 41. Lewitt MS, Yu VK, Rennie GC, Carter JN, Marel GM, Yue DK, et al. Effects of combined insulin-sulfonylurea therapy in type II patients. Diabetes Care. 1989;12(6):379-83. [PubMed: 2499443].
  • 42. Giugliano D, Quatraro A, Consoli G, Minei A, Ceriello A, De Rosa N, et al. Metformin for obese, insulin-treated diabetic patients: improvement in glycaemic control and reduction of metabolic risk factors. Eur J Clin Pharmacol. 1993;44(2):107-12. [PubMed: 8453955].
  • 43. Van Der Wal PS, Scheen A, Van Gaal L, Schmitt H, Heine RJ. Efficacy of bedtime NPH insulin alone, as compared to combination with metformin and/or glipizide in NIDDM patients with secondary failure to oral hypoglycemic agents. Diabetes. 1996;45(2S):286A.
  • 44. van der Wal PS, Scheen A, Van Gaal L, Schmitt H, Heine RJ. Predictors of glycaemic efficacy of four treatment strategies in NIDDM patients with secondary failure to oral hypoglycaemic agents. Netherlands J Med. 1996;4(48). A49.
  • 45. Schnack C, Biesenbach G, Kacerovsky G, Mihaljevic R, Pecnik I, Pieber T, et al. Evaluation of optimal therapy in type-2 diabetic patients insufficiently treated with sulfonylureas: The Austrian insulin intervention study. New York: Springer; 1996.
  • 46. Relimpio F, Pumar A, Losada F, Mangas MA, Acosta D, Astorga R. Adding metformin versus insulin dose increase in insulin-treated but poorly controlled Type 2 diabetes mellitus: an open-label randomized trial. Diabet Med. 1998;15(12):997-1002. doi: 10.1002/(SICI)1096-9136(1998120)15:12<997::AID-DIA716>3.0.CO;2-B. [PubMed: 9868971].
  • 47. Robinson AC, Burke J, Robinson S, Johnston DG, Elkeles RS. The effects of metformin on glycemic control and serum lipids in insulin-treated NIDDM patients with suboptimal metabolic control. Diabetes Care. 1998;21(5):701-5. [PubMed: 9589227].
  • 48. Hirsch IB. Metformin added to insulin therapy in poorly controlled type 2 diabetes. Diabetes Care. 1999;22(5):854. [PubMed: 10332695].
  • 49. Aviles-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1999;131(3):182-8. [PubMed: 10428734].
  • 50. Ponssen HH, Elte JW, Lehert P, Schouten JP, Bets D. Combined metformin and insulin therapy for patients with type 2 diabetes mellitus. Clin Ther. 2000;22(6):709-18. doi: 10.1016/S0149-2918(00)90005-5. [PubMed: 10929918].
  • 51. Hermann LS, Kalen J, Katzman P, Lager I, Nilsson A, Norrhamn O, et al. Long-term glycaemic improvement after addition of metformin to insulin in insulin-treated obese type 2 diabetes patients. Diabetes Obes Metab. 2001;3(6):428-34. [PubMed: 11903415].
  • 52. Wulffele MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, et al. Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care. 2002;25(12):2133-40. [PubMed: 12453950].
  • 53. Strowig SM, Aviles-Santa ML, Raskin P. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and troglitazone in type 2 diabetes. Diabetes Care. 2002;25(10):1691-8. [PubMed: 12351463].
  • 54. Altuntas Y, Ozen B, Ozturk B, Sengul A, Ucak S, Ersoy O, et al. Comparison of additional metformin or NPH insulin to mealtime insulin lispro therapy with mealtime human insulin therapy in secondary OAD failure. Diabetes Obes Metab. 2003;5(6):371-8. [PubMed: 14617222].
  • 55. Kokic S, Bukovic D, Radman M, Capkun V, Gabric N, Lesko V, et al. Lispro insulin and metformin versus other combination in the diabetes mellitus type 2 management after secondary oral antidiabetic drug failure. Coll Antropol. 2003;27(1):181-7. [PubMed: 12974145].
  • 56. Douek IF, Allen SE, Ewings P, Gale EA, Bingley PJ.Metformin Trial Group. Continuing metformin when starting insulin in patients with Type 2 diabetes: a double-blind randomized placebo-controlled trial. Diabet Med. 2005;22(5):634-40. doi: 10.1111/j.1464-5491.2005.01475.x. [PubMed: 15842521].
  • 57. Kabadi UM, Kabadi M. Comparative efficacy of glimepiride and/or metformin with insulin in type 2 diabetes. Diabetes Res Clin Pract. 2006;72(3):265-70. doi: 10.1016/j.diabres.2005.10.024. [PubMed: 16406190].
  • 58. Kvapil M, Swatko A, Hilberg C, Shestakova M. Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes. Diabetes Obes Metab. 2006;8(1):39-48. doi: 10.1111/j.1463-1326.2005.00492.x. [PubMed: 16367881].
  • 59. Ushakova O, Sokolovskaya V, Morozova A, Valeeva F, Zanozina O, Sazonova O, et al. Comparison of biphasic insulin aspart 30 given three times daily or twice daily in combination with metformin versus oral antidiabetic drugs alone in patients with poorly controlled type 2 diabetes: a 16-week, randomized, open-label, parallel-group trial conducted in russia. Clin Ther. 2007;29(11):2374-84. doi: 10.1016/j.clinthera.2007.11.017. [PubMed: 18158078].
  • 60. Vahatalo M, Ronnemaa T, Viikari J. Recognition of fasting or overall hyperglycaemia when starting insulin treatment in patients with type 2 diabetes in general practice. Scand J Prim Health Care. 2007;25(3):147-53. doi: 10.1080/02813430701507719. [PubMed: 17846932].
  • 61. Yilmaz H, Gursoy A, Sahin M, Guvener Demirag N. Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes. Acta Diabetol. 2007;44(4):187-92. doi: 10.1007/s00592-007-0004-9. [PubMed: 17726570].
  • 62. Civera M, Merchante A, Salvador M, Sanz J, Martinez I. Safety and efficacy of repaglinide in combination with metformin and bedtime NPH insulin as an insulin treatment regimen in type 2 diabetes. Diabetes Res Clin Pract. 2008;79(1):42-7. doi: 10.1016/j.diabres.2007.07.001. [PubMed: 17714824].
  • 63. Kooy A, De Jager J, Lehert P, Bets D, Wulffele MG, Donker AJ, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. 2009;169(6):616-25. doi: 10.1001/archinternmed.2009.20. [PubMed: 19307526].
  • 64. Kokic S, Kokic V, Krnic M, Miric L, Jovanovic Z, Orlic-Crncevic Z. Advantage of prandial insulin as a therapeutic approach in initial secondary pancreatic beta-cell exhaustion in type 2 diabetic patients. Diabetologia Croatica. 2010;39(1):37-42.
  • 65. Onuchin SG, Elsukova OS, Solov'ev OV, Onuchina EL. Capabilities of hypoglycemic therapy in women with decompensated type 2 diabetes mellitus. Ter Arkh. 2010;82(8):34-41. [PubMed: 20873243].
  • 66. Galani V. Comparison of Metformin and Insulin Monotherapy with Combined Metformin and Insulin Therapy in Patients of Type 2 Diabetes with HbA1c> 7%. Int J Pharm Biol Arch. 2011;2(1).
  • 67. Gram J, Henriksen JE, Grodum E, Juhl H, Hansen TB, Christiansen C, et al. Pharmacological treatment of the pathogenetic defects in type 2 diabetes: the randomized multicenter South Danish Diabetes Study. Diabetes Care. 2011;34(1):27-33. doi: 10.2337/dc10-0531. [PubMed: 20929990].
  • 68. Hemmingsen B, Christensen LL, Wetterslev J, Vaag A, Gluud C, Lund SS, et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ. 2012;344. e1771. doi: 10.1136/bmj.e1771. [PubMed: 22517929].
  • 69. Rosenstock J, Einhorn D, Hershon K, Glazer NB, Yu S, Pioglitazone 014 Study G. Efficacy and safety of pioglitazone in type 2 diabetes: a randomised, placebo-controlled study in patients receiving stable insulin therapy. Int J Clin Pract. 2002;56(4):251-7. [PubMed: 12074206].
  • 70. Mattoo V, Eckland D, Widel M, Duran S, Fajardo C, Strand J, et al. Metabolic effects of pioglitazone in combination with insulin in patients with type 2 diabetes mellitus whose disease is not adequately controlled with insulin therapy: results of a six-month, randomized, double-blind, prospective, multicenter, parallel-group study. Clin Ther. 2005;27(5):554-67. doi: 10.1016/j.clinthera.2005.05.005. [PubMed: 15978304].
  • 71. Mudaliar S, Chang AR, Aroda VR, Chao E, Burke P, Baxi S, et al. Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes. Diabetes Obes Metab. 2010;12(2):133-8. doi: 10.1111/j.1463-1326.2009.01126.x. [PubMed: 19889003].
  • 72. Fonseca V, Schweizer A, Albrecht D, Baron MA, Chang I, Dejager S. Addition of vildagliptin to insulin improves glycaemic control in type 2 diabetes. Diabetologia. 2007;50(6):1148-55. doi: 10.1007/s00125-007-0633-0. [PubMed: 17387446].
  • 73. Hong ES, Khang AR, Yoon JW, Kang SM, Choi SH, Park KS, et al. Comparison between sitagliptin as add-on therapy to insulin and insulin dose-increase therapy in uncontrolled Korean type 2 diabetes: CSI study. Diabetes Obes Metab. 2012;14(9):795-802. doi: 10.1111/j.1463-1326.2012.01600.x. [PubMed: 22443183].
  • 74. Barnett AH, Charbonnel B, Li J, Donovan M, Fleming D, Iqbal N. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy. Clin Drug Investig. 2013;33(10):707-17. doi: 10.1007/s40261-013-0107-8. [PubMed: 23949898].
  • 75. Woo VC, Berard LD, Bajaj HS, Ekoe JM, Senior PA. Considerations for Initiating a Sodium-Glucose Co-Transporter 2 Inhibitor in Adults With Type 2 Diabetes Using Insulin. Can J Diabetes. 2018;42(1):88-93. doi: 10.1016/j.jcjd.2017.01.009. [PubMed: 28579198].
  • 76. Buse JB, Bergenstal RM, Glass LC, Heilmann CR, Lewis MS, Kwan AY, 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(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. [PubMed: 21138825].
  • 77. DeVries JH, Bain SC, Rodbard HW, Seufert J, D'Alessio D, Thomsen AB, et al. Sequential intensification of metformin treatment in type 2 diabetes with liraglutide followed by randomized addition of basal insulin prompted by A1C targets. Diabetes Care. 2012;35(7):1446-54. doi: 10.2337/dc11-1928. [PubMed: 22584132].
  • 78. Li CJ, Li J, Zhang QM, Lv L, Chen R, Lv CF, et al. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity. Cardiovasc Diabetol. 2012;11:142. doi: 10.1186/1475-2840-11-142. [PubMed: 23153177].
  • 79. Seino Y, Min KW, Niemoeller E, Takami A, Efc 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(10):910-7. doi: 10.1111/j.1463-1326.2012.01618.x. [PubMed: 22564709].
  • 80. Riddle MC, Forst T, Aronson R, Sauque-Reyna L, Souhami E, Silvestre L. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine. Diabetes Care. 2013;36(9):2497-503. doi: 10.2337/dc12-2462.
  • 81. 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(9):2489-96. doi: 10.2337/dc12-2454. [PubMed: 23628617].
  • 82. Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014;37(10):2763-73. doi: 10.2337/dc14-0876. [PubMed: 25011946].
  • 83. Lane W, Weinrib S, Rappaport J, Hale C. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial. Diabetes Obes Metab. 2014;16(9):827-32. doi: 10.1111/dom.12286. [PubMed: 24589127].
  • 84. Mathieu C, Rodbard HW, Cariou B, Handelsman Y, Philis-Tsimikas A, Ocampo Francisco AM, et al. 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(7):636-44. doi: 10.1111/dom.12262. [PubMed: 24443830].
  • 85. Rosenstock J, Fonseca VA, Gross JL, Ratner RE, Ahren B, Chow FC, et al. Advancing basal insulin replacement in type 2 diabetes inadequately controlled with insulin glargine plus oral agents: a comparison of adding albiglutide, a weekly GLP-1 receptor agonist, versus thrice-daily prandial insulin lispro. Diabetes Care. 2014;37(8):2317-25. doi: 10.2337/dc14-0001. [PubMed: 24898300].
  • 86. Shao N, Kuang HY, Hao M, Gao XY, Lin WJ, Zou W. Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes. Diabetes Metab Res Rev. 2014;30(6):521-9. doi: 10.1002/dmrr.2561. [PubMed: 24823873].
  • 87. De Wit HM, Vervoort GM, Jansen HJ, De Grauw WJ, De Galan BE, Tack CJ. Liraglutide reverses pronounced insulin-associated weight gain, improves glycaemic control and decreases insulin dose in patients with type 2 diabetes: a 26 week, randomised clinical trial (ELEGANT). Diabetologia. 2014;57(9):1812-9. doi: 10.1007/s00125-014-3302-0. [PubMed: 24947583].
  • 88. Rosenstock J, Diamant M, Silvestre L, Souhami E, Zhou T, Fonseca V. Benefits of a fixed-ratio formulation of once-daily insulin glargine/lixisenatide (LixiLan) vs. glargine in type 2 diabetes (T2DM) inadequately controlled on metformin. USA: Amer Diabetes Assoc; 2014.
  • 89. Seino Y, Kaneko S, Fukuda S, Osonoi T, Shiraiwa T, Wang F, et al. Op72 combination therapy with liraglutide and insulin in japanese subjects with type 2 diabetes: The lira-add2insulin japan trial. Diabetes Res Clin Pract. 2014;106. S37.
  • 90. Conway JR, Ahmann A, Rodbard HW, Rosenstock J, Lahtela JT, Loredo L, et al. Efficacy and Safety of Liraglutide vs. Placebo When Added to Basal Insulin Analogues in Subjects with Type 2 Diabetes (LIRA-ADD2BASAL): A Randomized, Placebo-Controlled Trial. Can J Diabetes. 2014;38(5). S7. doi: 10.1016/j.jcjd.2014.07.017.
  • 91. Eng C, Kramer CK, Zinman B, Retnakaran R. Glucagon-like peptide-1 receptor agonist and basal insulin combination treatment for the management of type 2 diabetes: a systematic review and meta-analysis. Lancet. 2014;384(9961):2228-34. doi: 10.1016/S0140-6736(14)61335-0. [PubMed: 25220191].
  • 92. Maiorino MI, Chiodini P, Bellastella G, Capuano A, Esposito K, Giugliano D. Insulin and Glucagon-Like Peptide 1 Receptor Agonist Combination Therapy in Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Diabetes Care. 2017;40(4):614-24. doi: 10.2337/dc16-1957. [PubMed: 28325801].
  • 93. Aroda VR, Bailey TS, Cariou B, Kumar S, Leiter LA, Raskin P, et al. Effect of adding insulin degludec to treatment in patients with type 2 diabetes inadequately controlled with metformin and liraglutide: a double-blind randomized controlled trial (BEGIN: ADD TO GLP-1 Study). Diabetes Obes Metab. 2016;18(7):663-70. doi: 10.1111/dom.12661. [PubMed: 26990378].
  • 94. Seino Y, Kaneko S, Fukuda S, Osonoi T, Shiraiwa T, Nishijima K, et al. Combination therapy with liraglutide and insulin in Japanese patients with type 2 diabetes: A 36-week, randomized, double-blind, parallel-group trial. J Diabetes Investig. 2016;7(4):565-73. doi: 10.1111/jdi.12457. [PubMed: 27182042].
  • 95. Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540. [PubMed: 27273731].
  • 96. Rosenstock J, Guerci B, Hanefeld M, Gentile S, Aronson R, Tinahones FJ, et al. Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial. Diabetes Care. 2016;39(8):1318-28. doi: 10.2337/dc16-0014. [PubMed: 27222510].
  • 97. Flat-Sugar Trial Investigators. Glucose Variability in a 26-Week Randomized Comparison of Mealtime Treatment With Rapid-Acting Insulin Versus GLP-1 Agonist in Participants With Type 2 Diabetes at High Cardiovascular Risk. Diabetes Care. 2016;39(6):973-81. doi: 10.2337/dc15-2782. [PubMed: 27208320].
  • 98. Lingvay I, Perez Manghi F, Garcia-Hernandez P, Norwood P, Lehmann L, Tarp-Johansen MJ, et al. Effect of Insulin Glargine Up-titration vs Insulin Degludec/Liraglutide on Glycated Hemoglobin Levels in Patients With Uncontrolled Type 2 Diabetes: The DUAL V Randomized Clinical Trial. JAMA. 2016;315(9):898-907. doi: 10.1001/jama.2016.1252. [PubMed: 26934259].
  • 99. Aroda VR, Rosenstock J, Wysham C, Unger J, Bellido D, Gonzalez-Galvez G, et al. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide in Type 2 Diabetes Inadequately Controlled on Basal Insulin and Metformin: The LixiLan-L Randomized Trial. Diabetes Care. 2016;39(11):1972-80. doi: 10.2337/dc16-1495. [PubMed: 27650977].
  • 100. Rosenstock J, Diamant M, Aroda VR, Silvestre L, Souhami E, Zhou T, et al. Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial. Diabetes Care. 2016;39(9):1579-86. doi: 10.2337/dc16-0046. [PubMed: 27284114].
  • 101. Rosenstock J, Aronson R, Grunberger G, Hanefeld M, Piatti P, Serusclat P, et al. Benefits of LixiLan, a Titratable Fixed-Ratio Combination of Insulin Glargine Plus Lixisenatide, Versus Insulin Glargine and Lixisenatide Monocomponents in Type 2 Diabetes Inadequately Controlled on Oral Agents: The LixiLan-O Randomized Trial. Diabetes Care. 2016;39(11):2026-35. doi: 10.2337/dc16-0917. [PubMed: 27527848].
  • 102. Ahmann A, Rodbard HW, Rosenstock J, Lahtela JT, de Loredo L, Tornoe 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(11):1056-64. doi: 10.1111/dom.12539. [PubMed: 26179619].
  • 103. Buse JB, Vilsboll T, Thurman J, Blevins TC, Langbakke IH, Bottcher SG, et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care. 2014;37(11):2926-33. doi: 10.2337/dc14-0785. [PubMed: 25114296].
  • 104. Gough SC, Bode B, Woo V, Rodbard HW, Linjawi S, Poulsen P, et al. Efficacy and safety of a fixed-ratio combination of insulin degludec and liraglutide (IDegLira) compared with its components given alone: results of a phase 3, open-label, randomised, 26-week, treat-to-target trial in insulin-naive patients with type 2 diabetes. Lancet Diabetes Endocrinol. 2014;2(11):885-93. doi: 10.1016/S2213-8587(14)70174-3. [PubMed: 25190523].
  • 105. Lind M, Hirsch IB, Tuomilehto J, Dahlqvist S, Ahren B, Torffvit O, et al. Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (MDI Liraglutide trial). BMJ. 2015;351. h5364. doi: 10.1136/bmj.h5364. [PubMed: 26512041].
  • 106. Blonde L, Jendle J, Gross J, Woo V, Jiang H, Fahrbach JL, et al. Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study. Lancet. 2015;385(9982):2057-66. doi: 10.1016/S0140-6736(15)60936-9. [PubMed: 26009229].
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