Reduced Rates of Hypoglycemia in Type 1 or Type 2 Diabetes After Switching to Insulin Degludec: Results from the Italian Cohort of the ReFLeCT Study

Gian Paolo Fadini, Carla Giordano, Laura Salvi, Antonio Nicolucci, REFLECT Italian Study Group, Gian Paolo Fadini, Carla Giordano, Laura Salvi, Antonio Nicolucci, REFLECT Italian Study Group

Abstract

Introduction: To evaluate in an Italian real-world setting the safety and effectiveness of insulin degludec 100 units/mL, given once daily in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) after switching from other basal insulins.

Methods: ReFLeCT was a multicenter, prospective, observational study conducted across seven European countries which involved adult patients whose physician planned to switch their medication from basal insulin to insulin degludec. The primary outcome was the change in the number of hypoglycemic episodes before and after the switch to insulin degludec. Results are expressed as 12-month follow-up/baseline incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs).

Results: The Italian cohort of the ReFLect study comprised 148 patients with T1DM and 311 patients with T2DM. In patients with T1DM, the switch to insulin degludec was associated with significantly lower rates of overall (IRR 0.69, 95% CI 0.57-0.82), non-severe (IRR 0.72, 95% CI 0.60-0.85), and nocturnal hypoglycemia (IRR 0.46, 95% CI 0.31-0.69). Following the switch, hemoglobin A1c (HbA1c) levels decreased significantly by 0.35% (95% CI - 0.50 to - 0.20), with no significant changes in fasting plasma glucose (FPG) and basal insulin dose. Body weight increased by 0.83 kg (95% CI 0.16-1.50). In patients with T2DM, significant reductions in the rates of overall (IRR 0.40, 95% CI 0.29-0.55), non-severe (IRR 0.47, 95% CI 0.34-0.63), and nocturnal hypoglycemia (IRR 0.27, 95% CI 0.09-0.86) were documented. HbA1c and FPG decreased significantly by 0.45% (95% CI - 0.58 to - 0.31) and 0.90 mmol/L (95% CI - 1.21 to - 0.59], respectively, with no significant changes in basal insulin dose or body weight. Treatment satisfaction significantly improved in both diabetes types.

Conclusion: In Italian routine clinical practice, switching from other basal insulins to insulin degludec reduced the total episodes of hypoglycemia and improved glycemic control and treatment satisfaction in patients with T1DM and T2DM.

Trial registration: ClinicalTrials.gov NCT02392117.

Keywords: Hypoglycemia; Insulin degludec; Treatment satisfaction; Type 1 diabetes; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Study design. OD Once daily
Fig. 2
Fig. 2
Changes from baseline in rates of overall hypoglycemic events (a), non-severe hypoglycemic events (b), and nocturnal hypoglycemic events (c). CI Confidence interval, PYE patient-year, RR rate ratio, T1D/T2D type 1/type 2 diabetes mellitus
Fig. 3
Fig. 3
Change from baseline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels. Values in square brackets are the 95% CI. ETD Estimated treatment difference, ns non-statistically significant
Fig. 4
Fig. 4
Change from baseline in the Diabetes Treatment Satisfaction Questionnaire status version (DTSQ-s) total score

References

    1. Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes. 2008;57:3169–3176. doi: 10.2337/db08-1084.
    1. Workgroup on Hypoglycemia, American Diabetes Association Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005;28:1245–1249. doi: 10.2337/diacare.28.5.1245.
    1. Khunti K, Alsifri S, Aronson R, et al. 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. 2017;130:121–129. doi: 10.1016/j.diabres.2017.05.004.
    1. Novo Nordisk A/S. Tresiba (Insulin Degludec) summary of product characteristics. . Accessed Dec 2019.
    1. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab. 2012;14:859–864. doi: 10.1111/j.1463-1326.2012.01627.x.
    1. Heise T, Norskov M, Nosek L, Kaplan K, Famulla S, Haahr HL. Insulin degludec: lower day-to day and within-day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes. Diabetes Obes Metab. 2017;19:1032–1039. doi: 10.1111/dom.12938.
    1. Ratner RE, Gough SC, Mathieu C, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab. 2013;15:175–184. doi: 10.1111/dom.12032.
    1. Lane W, Bailey TS, Gerety G, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 1 diabetes: the SWITCH 1 randomized clinical trial. JAMA. 2017;318:33–44. doi: 10.1001/jama.2017.7115.
    1. Wysham C, Bhargava A, Chaykin L, et al. Effect of insulin degludec vs insulin glargine U100 on hypoglycemia in patients with type 2 diabetes: the SWITCH 2 randomized clinical trial. JAMA. 2017;318:45–56. doi: 10.1001/jama.2017.7117.
    1. Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med. 2017;377:723–732. doi: 10.1056/NEJMoa1615692.
    1. Yang W, Zilov A, Soewondo P, Bech OM, Sekkal F, Home PD. Observational studies: going beyond the boundaries of randomized controlled trials. Diabetes Res Clin Pract. 2010;88(Suppl 1):S3–9. doi: 10.1016/S0168-8227(10)70002-4.
    1. Sherman RE, Anderson SA, Dal Pan GJ, et al. Real-world evidence—what is it and what can it tell us? N Engl J Med. 2016;375:2293–2297. doi: 10.1056/NEJMsb1609216.
    1. Evans M, McEwan P, Foos V. Insulin degludec early clinical experience: does the promise from the clinical trials translate into clinical practice—a case-based evaluation. J Med Econ. 2015;18:96–105. doi: 10.3111/13696998.2014.975234.
    1. Siegmund T, Tentolouris N, Knudsen ST, et al. A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes. Diabetes Obes Metab. 2018;20:689–697. doi: 10.1111/dom.13149.
    1. Landstedt-Hallin L. Changes in HbA1c, insulin dose and incidence of hypoglycemia in patients with type 1 diabetes after switching to insulin degludec in an outpatient setting: an observational study. Curr Med Res Opin. 2015;31:1487–1493. doi: 10.1185/03007995.2015.1058252.
    1. Galasso S, Facchinetti A, Bonora BM, et al. Switching from twice-daily glargine or detemir to once-daily degludec improves glucose control in type 1 diabetes. An observational study. Nutr Metab Cardiovasc Dis. 2016;26:1112–1119. doi: 10.1016/j.numecd.2016.08.002.
    1. Bohn B, Zimmermann A, Wagner C, et al. Real-life experience of patients starting insulin degludec. A multicenter analysis of 1064 subjects from the German/Austrian DPV registry. Diabetes Res Clin Pract. 2017;129:52–58. doi: 10.1016/j.diabres.2017.03.031.
    1. Kaku K, Wolden ML, Hyllested-Winge J, Nortoft E. Insulin degludec in clinical practice: a review of japanese real-world data. Diabetes Ther. 2017;8:189–195. doi: 10.1007/s13300-017-0225-z.
    1. Ghosal S, Sinha B, Gangopadhyay KK. Insulin glargine versus insulin degludec in patients failing on oral therapy in type 2 diabetes: a retrospective real world comparative data from India. Diabetes Metab Syndr. 2016;10:161–165. doi: 10.1016/j.dsx.2016.01.013.
    1. Kobuke K, Yoneda M, Nakanishi S, Ohno H, Maeda S, Egusa G. Efficacy and safety of insulin degludec in Japanese patients with type 1 and type 2 diabetes: 24-week results from the observational study in routine clinical practice. J Diabetes Investig. 2016;7:94–99. doi: 10.1111/jdi.12373.
    1. Urakami T, Kuwabara R, Aoki M, Okuno M, Suzuki J. Efficacy and safety of switching from insulin glargine to insulin degludec in young people with type 1 diabetes. Endocr J. 2016;63:159–167. doi: 10.1507/endocrj.EJ15-0245.
    1. Suzuki J, Yamakawa T, Nagakura J, Shigematsu E, Kadonosono K, Terauchi Y. Efficacy of switching from insulin glargine to insulin degludec in patients with type 1 diabetes: a 16-week retrospective study. Diabetol Int. 2017;8:45–51. doi: 10.1007/s13340-016-0275-x.
    1. Shimoda S, Sato M, Sekigami T, et al. A 1-year, prospective, observational study of Japanese outpatients with type 1 and type 2 diabetes switching from insulin glargine or detemir to insulin degludec in basal-bolus insulin therapy (Kumamoto Insulin Degludec Observational study) J Diabetes Investig. 2016;7:703–710. doi: 10.1111/jdi.12496.
    1. Tibaldi J, Hadley-Brown M, Liebl A. A comparative effectiveness study of degludec and insulin glargine 300 U/mL in insulin-naïve patients with type 2 diabetes. Diabetes Obes Metab. 2018;21:1001–1009. doi: 10.1111/dom.13616.
    1. Fadini GP, Feher M, Hansen TK. Switching to degludec from other basal insulins is associated with reduced hypoglycemia rates: a prospective study. J Clin Endocrinol Metab. 2019;104:5977–5990. doi: 10.1210/jc.2019-01021.
    1. Bradley C (editor). The Diabetes Treatment Satisfaction Questionnaire. DTSQ. In: Bradley C, editor. Handbook of psychology and diabetes: a guide to psychological measurement in diabetes research and practice. Chur: Harwood Academic Publishers; 1994. p. 111–32.
    1. Ware JE, Kosinski M, Bjorner JB, Turner-Bowker DM, Maruish ME. User's manual for the SF-36 v2 health survey. Lincoln: QualityMetric; 2007.
    1. World Medical Association World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310:2191–2194. doi: 10.1001/jama.2013.281053.
    1. Seaquist ER, Anderson J, Childs B, et al. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 2013;36:1384–1395. doi: 10.2337/dc12-2480.
    1. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41:582–592.
    1. Giorda CB, Ozzello A, Gentile S, et al. Incidence and correlates of hypoglycemia in type 2 diabetes. The HYPOS-1 study. J Diabetes Metab. 2014;5:344.
    1. Giorda CB, Ozzello A, Gentile S, et al. Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study. Acta Diabetol. 2015;52:845–853. doi: 10.1007/s00592-015-0713-4.
    1. Holmes RS, Crabtree E, McDonagh MS. Comparative effectiveness and harms of long-acting insulins for type 1 and type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2019;21:984–992. doi: 10.1111/dom.13614.
    1. Pintaudi B, Lucisano G, Gentile S, et al. Correlates of diabetes-related distress in type 2 diabetes: findings from the benchmarking network for clinical and humanistic outcomes in diabetes (BENCH-D) study. J Psychosom Res. 2015;79:348–354. doi: 10.1016/j.jpsychores.2015.08.010.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe