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Effectiveness of insulin glargine U-300 versus insulin glargine U-100 on nocturnal hypoglycemia and glycemic control in type 1 and type 2 diabetes: a systematic review and meta-analysis

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Abstract

Aims

To assess the effectiveness of insulin glargine 300 ui/ml (Gla-300) compared with insulin glargine 100 ui/ml (Gla-100) on reducing nocturnal hypoglycemia and improving glycemic control in type 1 and type 2 diabetes patients.

Methods

We systematically searched in Medline, Embase, Web of Science, and Cochrane Central Register of Controlled Trials until July 4th, 2018. This study was registered with PROSPERO (CRD42017080134). We included randomized clinical trials comparing Gla-300 versus Gla-100 reporting the rate ratio or number of events of nocturnal hypoglycemia and HbA1c levels percentage or mmol/mol−1. The main outcome was the incidence rate ratio (RR) of nocturnal hypoglycemia events. The heterogeneity of results across studies was assessed using the I2 statistic. Fixed- and random-effect models were used to estimate pooled RRs.

Results

Nine studies were included in the meta-analysis, including 3977 adult patients. Compared with Gla-100, the use of Gla-300 reduced confirmed nocturnal hypoglycemia [RR = 0.81 (0.69, 0.95)] and clinically significant nocturnal hypoglycemia [RR = 0.75 (0.63, 0.91)]. Reductions in clinically significant nocturnal hypoglycemia events [RR = 0.64 (0.42, 0.97)] in type 1 diabetes patients were found. A small decrease in HbA1c levels in favor of Gla-300 in the pooled sample was identified [ES = − 0.08 (95% CI − 0.14, − 0.01)].

Conclusions

The best current evidence indicates that Gla-300 reduces the incidence of nocturnal hypoglycemia with slight improvements in glycemic control compared with Gla-100 in both type 1 and type 2 diabetes adult patients.

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References

  1. Miller KM, Foster NC, Beck RW et al (2015) Current state of type 1 diabetes treatment in the US: updated data from the T1D Exchange clinic registry. Diabetes Care 38:971–978

    Article  PubMed  Google Scholar 

  2. Khunti K, Wolden ML, Thorsted BL, Andersen M, Davies MJ (2013) Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care 36:3411–3417

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Khunti K, Alsifri S, Aronson R et al (2017) Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes. Diabetes Res Clin Pract 130:121–129

    Article  PubMed  CAS  Google Scholar 

  4. Fidler C, Elmelund Christensen T, Gillard S (2011) Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ 14:646–655

    Article  PubMed  Google Scholar 

  5. Graveling AJ, Frier BM (2017) The risks of nocturnal hypoglycaemia in insulin-treated diabetes. Diabetes Res Clin Pract 133:30–39

    Article  PubMed  CAS  Google Scholar 

  6. Dailey G, Lavernia F (2015) A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine. Diabetes Obes Metab 17:1107–1114

    Article  PubMed  CAS  Google Scholar 

  7. Becker RHA, Dahmen R, Bergmann K, Lehmann A, Jax T, Heise T (2015) New insulin glargine 300 Units.mL(-1) provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units.mL(-1). Diabetes Care 38:637–643

    PubMed  CAS  Google Scholar 

  8. Shiramoto M, Eto T, Irie S et al (2015) Single-dose new insulin glargine 300 U/ml provides prolonged, stable glycaemic control in Japanese and European people with type 1 diabetes. Diabetes Obes Metab 17:254–260

    Article  PubMed  CAS  Google Scholar 

  9. Brown MA, Davis CS, Fleming LW, Fleming JW (2016) The role of Toujeo®, insulin glargine U-300, in the treatment of diabetes mellitus. J Am Assoc Nurse Pract 28:503–509

    PubMed  Google Scholar 

  10. Lau IT, Lee KF, So WY, Tan K, Yeung VTF (2017) Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus. Diabetes Metab Syndr Obes 10:273–284

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62:1006–1012

    Article  PubMed  Google Scholar 

  12. Higgins J, Green S (eds) (2011) Cochrane handbook for systematic reviews of interventions. 5.1.0. In. The Cochrane Collaboration. (handbook.cochrane.org)

  13. Workgroup on Hypoglycemia AeDA (2005) Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 28:1245–1249

    Article  Google Scholar 

  14. Higgins JP, Altman DG, Gøtzsche PC et al (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  16. Cohen J (1988) Statistical power analysis for the behavioral sciences, Hillsdale

  17. Harbord RM, Egger M, Sterne JA (2006) A modified test for small-study effects in meta-analyses of controlled trials with binary endpoints. Stat Med 25:3443–3457

    Article  PubMed  Google Scholar 

  18. Home PD, Bergenstal RM, Bolli GB et al (2018) Glycaemic control and hypoglycaemia during 12 months of randomized treatment with insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 1 diabetes (EDITION 4). Diabetes Obes Metab 20:121–128

    Article  PubMed  CAS  Google Scholar 

  19. Bergenstal R, Bailey TS, Rodbard D et al (2017) Comparison of insulin glargine 300 Units/mL and 100 units/mL in adults with type 1 diabetes: continuous glucose monitoring profiles and variability using morning or evening injections. Diabetes Care 40:554–560

    Article  PubMed  CAS  Google Scholar 

  20. Matsuhisa M, Koyama M, Cheng X et al (2016) Sustained glycaemic control and less nocturnal hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 1 diabetes (EDITION JP 1 randomised 12-month trial including 6-month extension). Diabetes Res Clin Pract 122:133–140

    Article  PubMed  CAS  Google Scholar 

  21. Jinnouchi H, Koyama M, Amano A et al (2015) Continuous glucose monitoring during basal-bolus therapy using insulin glargine 300 U mL(-1) and glargine 100 U mL(-1) in Japanese people with type 1 diabetes mellitus: a crossover pilot study. Diabetes Therapy 6:143–152

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Bolli GB, Riddle MC, Bergenstal RM et al (2017) Glycaemic control and hypoglycaemia with insulin glargine 300U/mL versus insulin glargine 100U/mL in insulin-naïve people with type 2 diabetes: 12-month results from the EDITION 3 trial. Diabetes Metab 43:351–358

    Article  PubMed  CAS  Google Scholar 

  23. Terauchi Y, Koyama M, Cheng X et al (2017) Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension). Diabetes Metab 43:446–452

    Article  PubMed  CAS  Google Scholar 

  24. Yki-Jarvinen H, Bergenstal RM, Bolli GB et al (2015) Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12-month trial including 6-month extension. Diabetes Obes Metab 17:1142–1149

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Ritzel R, Harris SB, Baron H et al (2018) A randomized controlled trial comparing efficacy and safety of insulin glargine 300 units/mL versus 100 units/mL in older people with type 2 diabetes: results from the SENIOR Study. Diabetes Care 41:1672–1680

    Article  PubMed  CAS  Google Scholar 

  26. Riddle MC, Yki-Jarvinen H, Bolli GB et al (2015) One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension. Diabetes Obes Metab 17:835–842

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Home PD, Bergenstal RM, Bolli GB et al (2018) Glycaemic control and hypoglycaemia during 12 months of randomized treatment with insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 1 diabetes (EDITION 4). Diabetes Obes Metab 20(1):121–128

    Article  PubMed  CAS  Google Scholar 

  28. Ritzel R, Roussel R, Giaccari A, Vora J, Brulle-Wohlhueter C, Yki-Järvinen H (2018) Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes. Diabetes Obes Metab 20:541–548

    Article  PubMed  CAS  Google Scholar 

  29. Owens DR (2016) Pharmacokinetics and pharmacodynamics of insulin glargine 300 U/mL in the treatment of diabetes and their clinical relevance. Expert Opin Drug Metab Toxicol 12:977–987

    Article  PubMed  CAS  Google Scholar 

  30. Cryer PE (2005) Mechanisms of hypoglycemia-associated autonomic failure and its component syndromes in diabetes. Diabetes 54:3592–3601

    Article  PubMed  CAS  Google Scholar 

  31. Alsahli M, Gerich JE (2013) Hypoglycemia Endocrinol Metab Clin North Am 42:657–676

    Article  PubMed  Google Scholar 

  32. Zammitt NN, Frier BM (2005) Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care 28:2948–2961

    Article  PubMed  Google Scholar 

  33. Freemantle N, Chou E, Frois C et al (2016) Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis. BMJ Open 6:e009421

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gupta S, Wang H, Skolnik N et al (2018) Treatment dosing patterns and clinical outcomes for patients with type 2 diabetes starting or switching to treatment with insulin glargine (300 units per milliliter) in a real-world setting: a retrospective observational study. Adv Ther 35:43–55

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Zhou FL, Ye F, Berhanu P et al (2018) Real-world evidence concerning clinical and economic outcomes of switching to insulin glargine 300 units/mL vs other basal insulins in patients with type 2 diabetes using basal insulin. Diabetes Obes Metab 20:1293–1297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Health and Social Research Centre, Universidad de Castilla-La Mancha, C/ Santa Teresa Jornet, s/n, 16071, Cuenca, Spain

    Ana Díez-Fernández, Iván Cavero-Redondo, Diana P. Pozuelo-Carrascosa, Miriam Garrido-Miguel & Vicente Martínez-Vizcaíno

  2. Faculty of Nursing, Universidad de Castilla-La Mancha, Camino del Pozuelo, s/n, 16071, Cuenca, Spain

    Ana Díez-Fernández

  3. Department of Endocrinology and Nutrition, Ciudad Real General University Hospital, C/ Obispo Rafael Torija, s/n, 13005, Ciudad Real, Spain

    Jesús Moreno-Fernández

  4. Faculty of Health Sciences, Autonomous University of Chile, 5 y Medio Norte, 1670, Talca, Chile

    Vicente Martínez-Vizcaíno

Authors
  1. Ana Díez-Fernández
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  2. Iván Cavero-Redondo
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  3. Jesús Moreno-Fernández
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  4. Diana P. Pozuelo-Carrascosa
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  5. Miriam Garrido-Miguel
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  6. Vicente Martínez-Vizcaíno
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Corresponding author

Correspondence to Iván Cavero-Redondo.

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AD-F declares that she has no conflict of interest. IC-R declares that he has no conflict of interest. JM-F declares that he has no conflict of interest. DP-C declares that she has no conflict of interest. MG-M declares that she has no conflict of interest. VM-V declares that he has no conflict of interest.

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Díez-Fernández, A., Cavero-Redondo, I., Moreno-Fernández, J. et al. Effectiveness of insulin glargine U-300 versus insulin glargine U-100 on nocturnal hypoglycemia and glycemic control in type 1 and type 2 diabetes: a systematic review and meta-analysis. Acta Diabetol 56, 355–364 (2019). https://doi.org/10.1007/s00592-018-1258-0

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  • DOI: https://doi.org/10.1007/s00592-018-1258-0

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