Rationale for a titratable fixed-ratio co-formulation of a basal insulin analog and a glucagon-like peptide 1 receptor agonist in patients with type 2 diabetes

References

• Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care 2003;26:881–5
   PubMed Web of Science ®Google Scholar
• Riddle M, Umpierrez G, DiGenio A, et al. Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes. Diabetes Care 2011;34:2508–14
   PubMed Web of Science ®Google Scholar
• American Diabetes Association. Standards of Medical care in diabetes – 2018. Diabetes Care 2018;41(Suppl 1):S1–S159.
   PubMed Web of Science ®Google Scholar
• Blonde L, Brunton SA, Chava P, et al. Achievement of goal A1C (<7%) by U.S. patients with T2DM on basal insulin in both randomized, controlled trials (RCTs) and in clinical practice. Diabetes 2014;63:A235
   Google Scholar
• Brunton SA, Blonde L, Chava P, et al. Characteristics of patients with T2DM on basal insulin (INS) who do not achieve glycemic goals. Diabetologia 2014;57:S54
   Google Scholar
• Khunti K, Nikolajsen A, Thorsted BL, et al. Clinical inertia with regard to intensifying therapy in people with type 2 diabetes treated with basal insulin. Diabetes Obes Metab 2016;18:401–9
   PubMed Web of Science ®Google Scholar
• Shaefer C, Traylor L, Gao L, et al. Exploratory study of a dose–response curve for basal insulin. Diabetes 2015;64:A253
   Google Scholar
• Reid T, Gao L, Gill J, et al. How much is too much? Outcomes in patients using high-dose insulin glargine. Int J Clin Pract 2016;70:56–65
   PubMed Web of Science ®Google Scholar
• Handelsman Y, Bloomgarden ZT, Grunberger G, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract 2015;21(Suppl 1):1–87
   PubMed Web of Science ®Google Scholar
• Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm – 2016 Executive Summary. Endocr Pract 2018;24:91–120
   PubMed Web of Science ®Google Scholar
• Gough SC, Bode B, Woo V, 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;2:885–93
   PubMed Web of Science ®Google Scholar
• Buse JB, Vilsbøll T, Thurman J, et al. Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira). Diabetes Care 2014;37:2926–33
   PubMed Web of Science ®Google Scholar
• Gough SC, Bode BW, Woo VC, et al. One-year efficacy and safety of a fixed combination of insulin degludec and liraglutide in patients with type 2 diabetes: results of a 26-week extension to a 26-week main trial. Diabetes Obes Metab 2015;17:965–73
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Guerci B, Hanefeld M, 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;39:1318–28
   PubMed Web of Science ®Google Scholar
• Lingvay I, Pérez Manghi F, García-Hernández P, 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;315:898–907
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Diamant M, Aroda VR, 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;39:1579–86
   PubMed Web of Science ®Google Scholar
• Rosenstock J, Aronson R, Grunberger G, 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;39:2026–35
   PubMed Web of Science ®Google Scholar
• Aroda VR, Rosenstock J, Wysham C, 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;39:1972–80
   PubMed Web of Science ®Google Scholar
• Vijan S, Hayward RA, Ronis DL, et al. Brief report: the burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens. J Gen Intern Med 2005;20:479–82
   PubMed Web of Science ®Google Scholar
• Ross SA. Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes. Am J Med 2013;126(9 Suppl 1):S38–S48
   PubMed Web of Science ®Google Scholar
• García-Pérez LE, Alvarez M, Dilla T, et al. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther 2013;4:175–94
   PubMed Web of Science ®Google Scholar
• Peyrot M, Barnett AH, Meneghini LF, et al. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabet Med 2012;29:682–9
   PubMed Web of Science ®Google Scholar
• Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. Diabetes Care 2011;34(Suppl 2):S279–S84
   PubMed Web of Science ®Google Scholar
• Karagiannis T, Boura P, Tsapas A. Safety of dipeptidyl peptidase 4 inhibitors: a perspective review. Ther Adv Drug Saf 2014;5:138–46
   PubMedGoogle Scholar
• FDA safety warning [Internet]. Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. Silver Spring, MD: FDA; 2015. Available at: http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm [Last accessed April 9, 2017]
   Google Scholar
• Abu Hassan H, Tohid H, Mohd Amin R, et al. Factors influencing insulin acceptance among type 2 diabetes mellitus patients in a primary care clinic: a qualitative exploration. BMC Fam Pract 2013;14:164
   PubMed Web of Science ®Google Scholar
• Davies MJ, Gagliardino JJ, Gray LJ, et al. Real-world factors affecting adherence to insulin therapy in patients with Type 1 or Type 2 diabetes mellitus: a systematic review. Diabet Med 2013;30:512–24
   PubMed Web of Science ®Google Scholar
• Rubin RR, Peyrot M, Kruger DF, et al. Barriers to insulin injection therapy: patient and health care provider perspectives. Diabetes Educ 2009;35:1014–22
   PubMed Web of Science ®Google Scholar
• Evans M, Jensen HH, Bøgelund M, et al. Flexible insulin dosing improves health-related quality-of-life (HRQoL): a time trade-off survey. J Med Econ 2013;16:1357–65
   PubMedGoogle Scholar
• Pan F, Chernew ME, Fendrick AM. Impact of fixed-dose combination drugs on adherence to prescription medications. J Gen Intern Med 2008;23:611–14
   PubMed Web of Science ®Google Scholar
• Balena R, Hensley IE, Miller S, et al. Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature. Diabetes Obes Metab 2013;15:485–502
   PubMed Web of Science ®Google Scholar
• Baruah MP, Kalra S. The novel use of GLP-1 analogue and insulin combination in type 2 diabetes mellitus. Recent Pat Endocr Metab Immune Drug Discov 2012;6:129–35
   PubMedGoogle Scholar
• Arnolds S, Kuglin B, Kapitza C, et al. How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes. Int J Clin Pract 2010;64:1415–24
   PubMed Web of Science ®Google Scholar
• Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol 2012;8:728–42
   PubMed Web of Science ®Google Scholar
• Nauck MA, Kemmeries G, Holst JJ, et al. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes 201;60:1561–5
   PubMed Web of Science ®Google Scholar
• Rodbard HW. The clinical impact of GLP-1 receptor agonists in type 2 diabetes: focus on the long-acting analogs. Diabetes Technol Ther 2018;20:S233–S241
   PubMed Web of Science ®Google Scholar
• Bunck MC, Diamant M, Cornér A, 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;32:762–8
   PubMed Web of Science ®Google Scholar
• Bunck MC, Cornér A, Eliasson B, et al. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care 2011;34:2041–7
   PubMed Web of Science ®Google Scholar
• Seufert J, Gallwitz B. The extra-pancreatic effects of GLP-1 receptor agonists: a focus on the cardiovascular, gastrointestinal and central nervous systems. Diabetes Obes Metab 2014;16:673–88
   PubMed Web of Science ®Google Scholar
• Defronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009;58:773–95
   PubMed Web of Science ®Google Scholar
• Diamant M, Nauck MA, Shaginian R, et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care 2014;37:2763–73
   PubMed Web of Science ®Google Scholar
• Mathieu C, Rodbard HW, Cariou B, 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;16:636–44
   PubMed Web of Science ®Google Scholar
• Eng C, Kramer CK, Zinman B, et al. 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;384:2228–34
   PubMed Web of Science ®Google Scholar
• Linjawi S, Bode BW, Chaykin LB, et al. The efficacy of IDegLira (insulin degludec/liraglutide combination) in adults with type 2 diabetes inadequately controlled with a GLP-1 receptor agonist and oral therapy: DUAL III randomized clinical trial. Diabetes Ther 2017;8:101–14
   PubMed Web of Science ®Google Scholar
• Rodbard HW, Bode BW, Harris SB, et al. Safety and efficacy of insulin degludec/liraglutide (IDegLira) added to sulphonylurea alone or to sulphonylurea and metformin in insulin-naïve people with Type 2 diabetes: the DUAL IV trial. Diabet Med 2017;34:189–96
   PubMed Web of Science ®Google Scholar
• Harris SB, Kocsis G, Prager R, et al. Safety and efficacy of IDegLira titrated once weekly versus twice weekly in patients with type 2 diabetes uncontrolled on oral antidiabetic drugs: DUAL VI randomized clinical trial. Diabetes Obes Metab 2017;19:858–65
   PubMed Web of Science ®Google Scholar
• Billings LK, Doshi A, Gouet D, et al. Efficacy and safety of IDegLira versus basal-bolus insulin therapy in patients with type 2 diabetes uncontrolled on metformin and basal insulin: the DUAL VII randomized clinical trial. Diabetes Care 2018;41:1009–16
   PubMed Web of Science ®Google Scholar
• Soliqua prescribing information [Internet]. Bridgewater, NJ: Sanofi-aventis U.S. Updated 2016. Available at: http://products.sanofi.us/Soliqua100-33/Soliqua100-33.pdf [Last accessed April 9, 2017]
   Google Scholar
• Suliqua summary of product characteristics [Internet]. Paris, France: Sanofi-aventis Groupe. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_ Product_Information/human/004243/WC500224673.pdf [Last accessed April 9, 2017]
   Google Scholar
• Blonde L, Bailey TS, Chao J, et al. Characteristics and glycemic outcomes of T2D patients (PTS) titrated to 60 U/day with insulin glargine/lixisenatide fixed-ratio combination (iglarlixi) vs. insulin in the lixilan-L trial [abstract]. Diabetes 2017;66(Suppl 1):A294 (abstract 1107-P)
   Google Scholar
• Frias J, Hurst W, Newton J, et al. Impact of lixisenatide (LIXI) dose range on clinical outcomes with fixed-ratio combination (FRC) iglarlixi in patients with T2D [abstract]. Diabetes 2017;66(Suppl 1):A291–292 (abstract 1100-P)
   Google Scholar
• Handelsman Y, Chovanes C, Dex T, et al. Efficacy and safety of insulin glargine/lixisenatide fixed-ratio combination in elderly patients with T2D. American Diabetes Association - 76th Annual Scientific Sessions 2016;65:A246
   Google Scholar
• Skolnik N, Dupree RS, Johnson EL. iGlarLixi, a titratable once-daily fixed-ratio combination of basal insulin and lixisenatide for intensifying type 2 diabetes management for patients inadequately controlled on basal insulin with or without oral agents. Curr Med Res Opin 2017;33:2187–94
   PubMed Web of Science ®Google Scholar
• Frias JP, Domingo MP, Meneghini LF, et al. Shorter time to glycemic control with fixed-ratio combination of insulin glargine and lixisenatide compared with insulin glargine treatment alone [abstract]. Diabetes 2017;66(Suppl 1):A287 (abstract 1084-P)
   PubMed Web of Science ®Google Scholar
• Niemoeller E, Souhami E, Wu Y, et al. iGlarLixi reduces glycated hemoglobin to a greater extent than basal insulin regardless of levels at screening: post hoc analysis of LixiLan-L. Diabetes Ther 2018;9:373–82.
   PubMed Web of Science ®Google Scholar
• Xultophy prescribing information [Internet]. Bagsvaerd, Denmark: Novo Nordisk A/S. Updated 2016. Available at: http://www.novo-pi.com/xultophy10036.pdf [Last accessed April 9, 2017]
   Google Scholar
• Xultophy summary of product characteristics [Internet]. Bagsvaerd, Denmark: Novo Nordisk A/S. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPA R_-_Product_Information/human/002647/WC500177657.pdf [Last accessed April 9, 2017]
   Google Scholar
• Holst JJ, Buse JB, Rodbard HW, et al. IDegLira improves both fasting and postprandial glucose control as demonstrated using continuous glucose monitoring and a standardized meal test. J Diabetes Sci Technol 2015;10:389–97
   PubMedGoogle Scholar
• Aroda V, Jaekel E, Jarlov H, et al. Similar incidence of gastrointestinal side effects between IDegLira and non-glucagon-like peptide-1 receptor agonist comparators [abstract]. Diabetologia 2015;58(Suppl 1):S1–S607; abstract 833
   Google Scholar
• DeVries JH, Bain SC, Rodbard HW, 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;35:1446–54
   PubMed Web of Science ®Google Scholar
• Lin J, Lingohr-Smith M, Fan T. Real-world medication persistence and outcomes associated with basal insulin and glucagon-like peptide 1 receptor agonist free-dose combination therapy in patients with type 2 diabetes in the US. Clinicoecon Outcomes Res 2017;9:19–29
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care 2013;36(Suppl 2):S127–S138
   PubMed Web of Science ®Google Scholar