Improving postprandial hyperglycemia in patients with type 2 diabetes already on basal insulin therapy: Review of current strategies

Journal of Diabetes

Volumn 10, Issue 2, 2018, Pages 94-111

  Umpierrez, Guillermo E ^a   Bailey, Timothy S ^b   Carcia, Danielle ^c   Shaefer, Charles ^d   Shubrook, Jay H ^e   Skolnik, Neil ^c  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b AMCR Institute   (United States)

^c Department of Medicine   (United States)

^d University Health Systems   (United States)

^e TOURO UNIVERSITY CALIFORNIA   (United States)

Author keywords

diabetes mellitus type 2; glucagon like peptide 1; insulin; postprandial hyperglycemia

Indexed keywords

ALPHA GLUCOSIDASE INHIBITOR; DIPEPTIDYL PEPTIDASE IV INHIBITOR; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; HEMOGLOBIN A1C; INSULIN; INSULIN DERIVATIVE; PREMIXED INSULIN; SHORT ACTING INSULIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT;

CHRONIC KIDNEY FAILURE; CLINICAL EFFECTIVENESS; CLINICAL OUTCOME; COST EFFECTIVENESS ANALYSIS; COST OF ILLNESS; DIABETIC PATIENT; DIARRHEA; DISEASE SEVERITY; DRUG COST; DRUG SAFETY; EVIDENCE BASED MEDICINE; GASTROINTESTINAL DISEASE; GLYCEMIC CONTROL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INSULIN TREATMENT; MEDICAL EXPERT; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; ORTHOSTATIC HYPOTENSION; PATIENT CARE; PATIENT SAFETY; POSTPRANDIAL STATE; PRACTICE GUIDELINE; PRIMARY MEDICAL CARE; PRIORITY JOURNAL; REVIEW; RISK BENEFIT ANALYSIS; TREATMENT RESPONSE; VOMITING; ANALYSIS; COMPLICATION; GLUCOSE BLOOD LEVEL;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN, SHORT-ACTING;

EID: 85028337633     PISSN: 17530393     EISSN: 17530407     Source Type: Journal    
DOI: 10.1111/1753-0407.12576     Document Type: Review

References (129)

1. Centers of Disease Control and Prevention. National Diabetes Report, 2014. 2014. Available from: http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf (accessed 7 April 2015).
2. Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in type 2 diabetes: A patient-centered approach: Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012; 35: 1364–1379.
3. Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin. Diabetes. 2008; 26: 77–82.
4. Inzucchi SE, Bergenstal RM, Buse JB 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: 140–149.
5. Stark Casagrande S, Fradkin JE, Saydah SH, Rust KF, Cowie CC. The prevalence of meeting A1C, blood pressure, and LDL goals among people with diabetes, 1988–2010. Diabetes Care. 2013; 36: 2271–2279.
6. Handelsman Y, Mechanick JI, Blonde L et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2015; 21 (Suppl. 1): 1–86.
7. 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. 2016; 22: 84–113.
8. Riddle M, Umpierrez G, DiGenio A, Zhou R, Rosenstock J. 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: 2508–2514.
9. Shaefer C, Traylor L, Gao L, Dex T, Sepe P, Skolnik N. Exploratory study of a dose–response curve for basal insulin. Diabetes. 2015; 64 (Suppl. 1): A253 (Abstract).
10. Zisman A, Morales F, Stewart J, Stuhr A, Vlajnic A, Zhou R. BeAM value: An indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin. BMJ Open Diabetes Res Care. 2016; 4: e000171.
11. 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: 2763–2773.
12. Buse JB, Bergenstal RM, Glass LC 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: 103–112.
13. Rosenstock J, Fonseca VA, Gross JL 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: 2317–2325.
14. Rosenstock J, Guerci B, Paranjape S, Berria R, Souhami E, Aroda VR. Improved glucose control without increased hypoglycemia risk at any level of HbA1c reduction with insulin glargine/lixisenatide alone both added on to metformin in type 2 diabetes (T2DM). Diabetes. 2015; 64 (Suppl. 1): A44 (Abstract).
15. Shao N, Kuang HY, Hao M, Gao XY, Lin WJ, Zou W. Effects of exenatide on obesity and NAFLD with elevated liver enzymes in patients with type 2 diabetes. Diabetes Metab Res Rev. 2014; 30: 521–529.
16. 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: 636–644.
17. Haas B, Eckstein N, Pfeifer V, Mayer P, Hass MD. Efficacy, safety and regulatory status of SGLT2 inhibitors: Focus on canagliflozin. Nutr Diabetes. 2014; 4: e143.
18. Rosenstock J, Aguilar-Salinas C, Klein E et al. Effect of saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes. Curr Med Res Opin. 2009; 25: 2401–2411.
19. Rosak C, Mertes G. Critical evaluation of the role of acarbose in the treatment of diabetes: Patient considerations. Diabetes Metab Syndr Obes. 2012; 5: 357–367.
20. Lankisch MR, Ferlinz KC, Leahy JL, Scherbaum WA, Orals PlusApidra and LANTUS (OPAL) Study Group. Introducing a simplified approach to insulin therapy in type 2 diabetes: A comparison of two single-dose regimens of insulin glulisine plus insulin glargine and oral antidiabetic drugs. Diabetes Obes Metab. 2008; 10: 1178–1185.
21. Owens DR, Luzio SD, Sert-Langeron C, Riddle MC. Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: A 6-month “proof-of-concept” study. Diabetes Obes Metab. 2011; 13: 1020–1027.
22. Davidson MB, Raskin P, Tanenberg RJ, Vlajnic A, Hollander P. A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure. Endocr Pract. 2011; 17: 395–403.
23. Raccah D, Haak TJ, Huet D et al. Comparison of stepwise addition of prandial insulin to a basal-bolus regimen when basal insulin is insufficient for glycaemic control in type 2 diabetes: Results of the OSIRIS study. Diabetes Metab. 2012; 38: 507–514.
24. Riddle MC, Rosenstock J, Vlajnic A, Gao L. Randomized, 1-year comparison of three ways to initiate and advance insulin for type 2 diabetes: Twice-daily premixed insulin versus basal insulin with either basal-plus one prandial insulin or basal-bolus up to three prandial injections. Diabetes Obes Metab. 2014; 16: 396–402.
25. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DH. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): A randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol. 2014; 2: 30–37.
26. Giugliano D, Maiorino MI, Bellastella G, Chiodini P, Ceriello A, Esposito K. Efficacy of insulin analogs in achieving the hemoglobin A1C target of <7% in type 2 diabetes: Meta-analysis of randomized controlled trials. Diabetes Care. 2011; 34: 510–517.
27. Ilag LL, Kerr L, Malone JK, Tan MH. Prandial premixed insulin analogue regimens versus basal insulin analogue regimens in the management of type 2 diabetes: An evidence-based comparison. Clin Ther. 2007; 29 (Spec. No.): 1254–1270.
28. Ahrén B. Avoiding hypoglycemia: A key to success for glucose-lowering therapy in type 2 diabetes. Vasc Health Risk Manag. 2013; 9: 155–163.
29. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: A meta-analysis. Diabetes Res Clin Pract. 2008; 81: 184–189.
30. Mannucci E, Monami M, Marchionni N. Short-acting insulin analogues vs. regular human insulin in type 2 diabetes: A meta-analysis. Diabetes Obes Metab. 2009; 11: 53–59.
31. Tibaldi JM. Evolution of insulin: From human to analog. Am J Med. 2014; 127 (Suppl.): S25–S38.
32. Kulozik F, Hasslacher C. Insulin requirements in patients with diabetes and declining kidney function: Differences between insulin analogues and human insulin? Ther Adv Endocrinol Metab. 2013; 4: 113–121.
33. 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.
34. 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: 2926–2933.
35. 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: 1812–1819.
36. 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: 827–832.
37. Li CJ, Li J, Zhang QM 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.
38. 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: 910–977.
39. Riddle MC, Aronson R, Home 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: 2489–2496.
40. Riddle MC, Forst T, Aronson R et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: A 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). Diabetes Care. 2013; 36: 2497–2503.
41. Levin P, Wei W, Wang L, Pan C, Douglas D, Baser O. Combination therapy with insulin glargine and exenatide: Real-world outcomes in patients with type 2 diabetes. Curr Med Res Opin. 2012; 28: 439–446.
42. Levin PA, Mersey JH, Zhou S, Bromberger LA. Clinical outcomes using long-term combination therapy with insulin glargine and exenatide in patients with type 2 diabetes mellitus. Endocr Pract. 2012; 18: 17–25.
43. 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: 1446–1454.
44. Trujillo JM, Nuffer W, Ellis SL. GLP-1 receptor agonists: A review of head-to-head clinical studies. Ther Adv Endocrinol Metab. 2015; 6: 19–28.
45. Buse JB, Rosenstock J, Sesti G et al. 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.
46. Buse JB, Nauck M, Forst T et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet. 2013; 381: 117–124.
47. Rosenstock J, Raccah D, Korányi L et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: A 24-week, randomized, open-label, active-controlled study (GetGoal-X). Diabetes Care. 2013; 36: 2945–2951.
48. Pratley RE, Nauck MA, Barnett AH et al. 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.
49. Dungan KM, Povedano ST, Forst T et al. Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): A randomised, open-label, phase 3, non-inferiority trial. Lancet. 2014; 384: 1349–1357.
50. Meier JJ, Rosenstock J, Hincelin-Méry A et al. Contrasting effects of lixisenatide and liraglutide on postprandial glycemic control, gastric emptying, and safety parameters in patients with type 2 diabetes on optimized insulin glargine with or without metformin: A randomized, open-label trial. Diabetes Care. 2015; 38: 1263–1273.
51. Garber AJ. Long-acting glucagon-like peptide 1 receptor agonists: A review of their efficacy and tolerability. Diabetes Care. 2011; 34 (Suppl. 2): S279–S284.
52. Balena R, Hensley IE, Miller S, Barnett AH. Combination therapy with GLP-1 receptor agonists and basal insulin: A systematic review of the literature. Diabetes Obes Metab. 2013; 15: 485–502.
53. Dalal MR, Xie L, Baser O, DiGenio A. Adding rapid-acting insulin or GLP-1 receptor agonist to basal insulin: Outcomes in a community setting. Endocr Pract. 2015; 21: 68–76.
54. Li L, Shen J, Bala MM et al. Incretin treatment and risk of pancreatitis in patients with type 2 diabetes mellitus: Systematic review and meta-analysis of randomised and non-randomised studies. BMJ. 2014; 348: g2366.
55. Bjerre Knudsen L, Madsen LW, Andersen S et al. Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation. Endocrinology. 2010; 151: 1473–1486.
56. Knauf G, Gotfredsen C, Pilling A et al. GLP-1 receptor agonists and the thyroid: C-Cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology. 2012; 153: 1538–1547.
57. Amylin Pharmaceuticals, Inc. Byetta Prescribing Information. 2009. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021773s9s11s18s22s25lbl.pdf (accessed 12 April 2017).
58. Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists: Efficacy and safety in diabetes and beyond. Drugs Context. 2015; 4: 212283.
59. Pfeffer MA, Claggett B, Diaz R et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015; 373: 2247–2257.
60. Marso SP, Poulter NR, Nissen SE et al. Design of the liraglutide effect and action in diabetes: Evaluation of cardiovascular outcome results (LEADER) trial. Am Heart J. 2013; 166: 823–830.
61. Marso SP, Bain SC, Consoli A et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375: 1834–1844.
62. Marso SP, Daniels GH, Brown-Frandsen K et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016; 375: 311–322.
63. Scheen AJ. DPP-4 inhibitors in the management of type 2 diabetes: A critical review of head-to-head trials. Diabetes Metab. 2012; 38: 89–101.
64. Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: A systematic review and mixed treatment comparison. Diabetes Ther. 2014; 5: 1–41.
65. Rosenstock J, Rendell MS, Gross JL, Fleck PR, Wilson CA, Mekki Q. Alogliptin added to insulin therapy in patients with type 2 diabetes reduces HbA(1C) without causing weight gain or increased hypoglycaemia. Diabetes Obes Metab. 2009b; 11: 1145–1152.
66. Hong ES, Khang AR, Yoon JW 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: 795–802.
67. Yki-Järvinen H, Rosenstock J, Durán-Garcia S et al. Effects of adding linagliptin to basal insulin regimen for inadequately controlled type 2 diabetes: A ≥52-week randomized, double-blind study. Diabetes Care. 2013; 36: 3875–3881.
68. Barnett AH, Charbonnel B, Donovan M, Fleming D, Chen R. Effect of saxagliptin as add-on therapy in patients with poorly controlled type 2 diabetes on insulin alone or insulin combined with metformin. Curr Med Res Opin. 2012; 28: 513–523.
69. 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: 707–717.
70. Takai M, Ishikawa M, Maeda H et al. Safety and efficacy of adding sitagliptin to insulin in patients with type 2 diabetes: The ASSIST-K study. Diabetes Res Clin Pract. 2014; 103: e30–e33.
71. Karagiannis T, Boura P, Tsapas A. Safety of dipeptidyl peptidase 4 inhibitors: A perspective review. Ther Adv Drug Saf. 2014; 5: 138–146.
72. Scirica BM, Bhatt DL, Braunwald E et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013; 369: 1317–1326.
73. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA Warns that DPP-4 Inhibitors for Type 2 Diabetes May Cause Severe Joint Pain. 2015. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm459579.htm (accessed 27 April 2016).
74. Egan AG, Blind E, Dunder K et al. Pancreatic safety of incretin-based drugs: FDA and EMA assessment. N Engl J Med. 2014; 370: 794–797.
75. Abe M, Okada K. DPP-4 inhibitors in diabetic patients with chronic kidney disease and end-stage kidney disease on dialysis in clinical practice. Contrib Nephrol. 2015; 185: 98–115.
76. Russo E, Penno G, Del Prato S. Managing diabetic patients with moderate or severe renal impairment using DPP-4 inhibitors: Focus on vildagliptin. Diabetes Metab Syndr Obes. 2013; 6: 161–170.
77. Weir DL, McAlister FA, Senthilselvan A, Minhas-Sandhu JK, Eurich DT. Sitagliptin use in patients with diabetes and heart failure: A population-based retrospective cohort study. JACC Heart Fail. 2014; 2: 573–582.
78. White WB, Cannon CP, Heller SR et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013; 369: 1327–1335.
79. Seoyoung CK, Glynn RJ, Liu J, Everett BM, Goldfine AB. Dipeptidyl peptidase-4 inhibitors do not increase the risk of cardiovascular events in type 2 diabetes: A cohort study. Acta Diabetol. 2014; 51: 1015–1023.
80. Zannad F, Cannon CP, Cushman WC et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: A multicentre, randomised, double-blind trial. Lancet. 2015; 385: 2067–2076.
81. Green JB, Bethel MA, Armstrong PW et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 373: 232–242.
82. Takeda. FDA Advisory Committee Reviews Takeda’s Alogliptin EXAMINE Cardiovascular Safety Outcomes Trial. 2015. Available from: https://www.takeda.com/news/2015/20150415_6961.html (accessed 14 May 2015).
83. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: Basic physiology and consequences. Diab Vasc Dis Res. 2015; 12: 78–89.
84. Polidori D, Sha S, Mudaliar S et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: Results of a randomized, placebo-controlled study. Diabetes Care. 2013; 36: 2154–2161.
85. Devineni D, Morrow L, Hompesch M et al. Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin. Diabetes Obes Metab. 2012; 14: 539–545.
86. Neal B, Perkovic V, de Zeeuw D et al. Efficacy and safety of canagliflozin, an inhibitor of sodium–glucose cotransporter 2, when used in conjunction with insulin therapy in patients with type 2 diabetes. Diabetes Care. 2015; 38: 403–411.
87. Wilding JP, Norwood P, T’joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: Applicability of a novel insulin-independent treatment. Diabetes Care. 2009; 32: 1656–1662.
88. Rosenstock J, Jelaska A, Zeller C, Kim G, Broedl UC, Woerle HJ. Impact of empagliflozin added-on to basal insulin in type 2 diabetes inadequately controlled on basal insulin: A 78-week randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2015; 17: 936–948.
89. Abdul-Ghani M. Where does combination therapy with an SGLT2 inhibitor plus a DPP-4 inhibitor fit in the management of type 2 diabetes? Diabetes Care. 2015; 38: 373–375.
90. Lexicon Pharmaceuticals. Phase 3b Clinical Trial of Sotagliflozin for T2D. 2016. Available from: http://www.lexpharma.com/pipeline/sotagliflozin/t2d-clinical-results (accessed 9 June 2017).
91. Zambrowicz B, Freiman J, Brown PM et al. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012; 92: 158–169.
92. Janssen Pharmaceuticals, Inc. INVOKANA (canagliflozin) Prescribing Information. 2016. Available from: https://www.invokanahcp.com/prescribing-information.pdf (accessed 22 April 2015).
93. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA Revises Labels of SGLT2 Inhibitors for Diabetes to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections. 2015. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm (accessed 13 January 2015).
94. Taylor SI, Blau JE, Rother KI. Possible adverse effects of SGLT2 inhibitors on bone. Lancet Diabetes Endocrinol. 2015; 3: 8–10.
95. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium–glucose cotransporter 2 inhibition. Diabetes Care. 2015; 38: 1687–1693.
96. US Food and Drug Administration (FDA). FDA Strengthens Fracture Warning for Canagliflozin. 2015. Available from: http://www.medscape.com/viewarticle/850835 (accessed 9 June 2017).
97. Watts NB, Bilezikian JP, Usiskin K et al. Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2016; 101: 157–166.
98. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA Revises Label of Diabetes Drug Canagliflozin (Invokana, Invokamet) to Include Updates on Bone Fracture Risk and New Information on Decreased Bone Mineral Density. 2015. Available from: https://www.fda.gov/Drugs/DrugSafety/ucm461449.htm (accessed 9 June 2017).
99. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA Warns that SGLT2 Inhibitors for Diabetes May Result in a Serious Condition of Too Much Acid in the Blood. 2015. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm (accessed 8 May 2015).
100. US Food and Drug Administration (FDA). FDA Drug Safety Communication: FDA Strengthens Kidney Warnings for Diabetes Medicines Canagliflozin (Invokana, Invokamet) and Dapagliflozin (Farxiga, Xigduo XR). 2016. Available from: http://www.fda.gov/Drugs/DrugSafety/ucm505860.htm (accessed 19 October 2016).
101. Jensen ML, Persson F, Andersen GS et al. Incidence of ketoacidosis in the Danish type 2 diabetes population before and after introduction of sodium–glucose cotransporter 2 inhibitors: A nationwide, retrospective cohort study, 1995–2014. Diabetes Care. 2017; 40: e57–e58.
102. European Medicines Agency. Review of Diabetes Medicines Called SGLT2 Inhibitors Started. 2015. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/SGLT2_inhibitors/human_referral_prac_000052.jsp&mid=WC0b01ac05805c516f (accessed 18 August 2015).
103. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373: 2117–2128.
104. Janssen Research & Development, LLC. CANVAS – CANagliflozin cardioVascular Assessment Study (CANVAS). 2017. Available from: https://clinicaltrials.gov/ct2/show/NCT01032629 (accessed 25 April 2016).
105. AstraZeneca. Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58). 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01730534 (accessed 25 April 2016).
106. Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C. Alpha-glucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005; 18: CD003639.
107. Lee MY, Choi DS, Lee MK et al. Comparison of acarbose and voglibose in diabetes patients who are inadequately controlled with basal insulin treatment: Randomized, parallel, open-label, active-controlled study. J Korean Med Sci. 2014; 29: 90–97.
108. Kim MK, Suk JH, Kwon MJ et al. 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.
109. 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: 187–192.
110. Hanefeld M. Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes. Cardiovasc Diabetol. 2007; 6: 20.
111. Chiasson JL, Josse RG, Gomis R et al. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: The STOP-NIDDM trial. JAMA. 2003; 290: 486–494.
112. Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: Meta-analysis of seven long-term studies. Eur Heart J. 2004; 25: 10–16.
113. Barnett AH, Huisman H, Jones R, von Eynatten M, Patel S, Woerle HJ. Linagliptin for patients aged 70 years or older with type 2 diabetes inadequately controlled with common antidiabetes treatments: A randomised, double-blind, placebo-controlled trial. Lancet. 2013; 382: 1413–1423.
114. Reid T. Choosing GLP-1 receptor agonists or DPP-4 inhibitors: Weighing the clinical trial evidence. Clin Diabetes. 2012; 30: 3–12.
115. US Food and Drug Administration. Information for Healthcare Professionals: Reports of Altered Kidney Function in Patients Using Exenatide (Marketed as Byetta). 2013. Available from: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm188656.htm (accessed 9 June 2017).
116. US Food and Drug Administration. BYDUREON. Full Prescribing Information. 2012. Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/022200s000lbl.pdf (accessed 9 June 2017).
117. Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2016; 17: 1074–1094.
118. Saunders R, Lian J, Karolicki B, Valentine W. The cost-effectiveness and budget impact of stepwise addition of bolus insulin in the treatment of type 2 diabetes: Evaluation of the FullSTEP trial. J Med Econ. 2014; 17: 827–836.
119. Levin PA, Zhang Q, Mersey JH et al. Glycemic control with insulin glargine plus insulin glulisine versus premixed insulin analogues in real-world practices: A cost-effectiveness study with a randomized pragmatic trial design. Clin Ther. 2011; 33: 841–850.
120. Geng J, Yu H, Mao Y, Zhang P, Chen Y. Cost effectiveness of dipeptidyl peptidase-4 inhibitors for type 2 diabetes. Pharmacoeconomics. 2015; 33: 581–597.
121. Novo Nordisk. Novo Nordisk Receives US FDA Approval for Tresiba® and Ryzodeg® 70/30. 2015. Available from: http://www.novonordisk.com/media/news-details.1954709.html (accessed 16 September 2015).
122. Sanofi. Sanofi Receives FDA Approval of Once-Daily Basal Insulin Toujeo. 2015. Available from: http://www.news.sanofi.us/2015-02-25-Sanofi-Receives-FDA-Approval-of-Once-Daily-Basal-Insulin-Toujeo (accessed 9 June 2017).
123. Heise T, Tack CJ, Cuddihy R et al. A new-generation ultra-long-acting basal insulin with a bolus boost compared with insulin glargine in insulin-naive people with type 2 diabetes: A randomized, controlled trial. Diabetes Care. 2011; 34: 669–674.
124. Fulcher GR, Christiansen JS, Bantwal G et al. Comparison of insulin degludec/insulin aspart and biphasic insulin aspart 30 in uncontrolled, insulin-treated type 2 diabetes: A phase 3a, randomized, treat-to-target trial. Diabetes Care. 2014; 37: 2084–2090.
125. Kaneko S, Chow F, Choi DS et al. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: A 26-week, randomised, treat-to-target trial. Diabetes Res Clin Pract. 2015; 107: 139–147.
126. Buse JB, Manghi PFC, Garcia-Hernandez PA et al. Insulin degludec/liraglutide (IDegLira) is superior to insulin glargine (IG) in A1C reduction, risk of hypoglycemia, and weight change: Dual V study. Diabetes. 2015; 64 (Suppl. 1): A43 (Abstract).
127. 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: 885–893.
128. 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: 965–973.
129. García-Pérez LE, Alvarez M, Dilla T, Gil-Guillén V, Orozco-Beltrán D. Adherence to therapies in patients with type 2 diabetes. Diabetes Ther. 2013; 4: 175–194.