Evaluating the Effectiveness of Switching to Insulin Degludec from Other Basal Insulins in a Real-World Canadian Population with Type 1 or Type 2 Diabetes: The CAN-TREAT Study

Stewart B Harris, Olubukola Ajala, Basel Bari, Joanne Liutkus, Jina Hahn, Oliver Martyn, Deborah Zwicker, Stewart B Harris, Olubukola Ajala, Basel Bari, Joanne Liutkus, Jina Hahn, Oliver Martyn, Deborah Zwicker

Abstract

Introduction: The aim of the study was to examine glycaemic control and safety of insulin degludec (degludec) in patients with either type 1 diabetes (T1D) or type 2 diabetes (T2D) under routine care settings in Canada.

Methods: Data were extracted from medical records of adults with T1D or T2D who switched to degludec (± prandial insulin) from another basal insulin (± prandial insulin) ≥ 6 months prior to data collection. The primary endpoint was change in glycated haemoglobin (HbA1c) at 6 ± 3 months after degludec initiation. Secondary endpoints included change in hypoglycaemia rate in the 6 months before versus the 6 months after switching, and change in mean total daily insulin dose.

Results: Of 667 patients assessed for eligibility, 626 were included. After 6 ± 3 months, HbA1c decreased from baseline in patients with T1D (- 0.3% [- 0.42, - 0.14]95% CI; p < 0.001) and in patients with T2D (- 0.4% [- 0.55, - 0.30]95% CI; p < 0.001). In patients with T1D, there were significant reductions in the rates of overall (rate ratio [RR] 0.70), non-severe (RR 0.69), non-severe nocturnal (RR 0.36), and severe nocturnal hypoglycaemia (RR 0.12; all p ≤ 0.004). In patients with T2D there was a significant reduction in non-severe nocturnal hypoglycaemia (RR 0.22; p < 0.001). Mean daily basal insulin dose decreased in patients with T1D (- 1.6 units [- 2.8, - 0.4]95% CI; p = 0.008); there was no significant change in patients with T2D (- 0.6 units [- 2.7, 1.4]95% CI; p = 0.543).

Conclusion: In routine clinical practice, improved glycaemic control was observed in patients with T1D or T2D switching to insulin degludec from other basal insulins, with either improvement or no change in hypoglycaemia rates.

Trial registration: ClinicalTrials.gov NCT03674866.

Keywords: Canada; Glycaemia; Glycaemic control; Hypoglycaemia; Insulin degludec; Real-world; Type 1 diabetes; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Change from baseline to 6 ± 3 months after initiating degludec in HbA1c (a) and FPG (b). P values were determined using a paired t test. Data are mean (95% CI) values based on a paired t test comparing observed data at baseline and 6 months. Only patients with data at baseline and 6 ± 3 months after degludec initiation were included in the analysis. HbA1c glycated haemoglobin, CI confidence interval, FPG fasting plasma glucose, T1D type 1 diabetes, T2D type 2 diabetes
Fig. 2
Fig. 2
Proportion of patients achieving HbA1c targets at baseline and 6 ± 3 months after initiating degludec in T1D (a) and T2D (b). Baseline refers to the most recent measurement prior to initiating degludec (> 3 months prior to switch). After initiating degludec refers to the period between 0 and 6 months after initiating degludec. None of the comparisons presented were statistically significant. HbA1c glycated haemoglobin, T1D type 1 diabetes, T2D type 2 diabetes
Fig. 3
Fig. 3
Hypoglycaemia rates in the 6-month periods before and after initiating degludec in patients with T1D (a) and T2D (b). Hypoglycaemic events were those recorded in patient medical records and were categorised by the treating physician or an appropriately trained delegate at data extraction, based on the information recorded in the medical records. There were more patients with missing data in the overall hypoglycaemia category than in the non-severe hypoglycaemia category. Before initiating degludec refers to the period between 6 and 0 months before initiating degludec. After initiating degludec refers to the period between 0 and 6 months after initiating degludec. PYO patient-year of observation, T1D type 1 diabetes, T2D type 2 diabetes, RR rate ratio, CI confidence interval, NS not significant

References

    1. Heise T, Hovelmann U, Nosek L, Hermanski L, Bottcher SG, Haahr H. Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine. Expert Opin Drug Metab Toxicol. 2015;11:1193–1201. doi: 10.1517/17425255.2015.1058779.
    1. Heise T, Nosek L, Bottcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab. 2012;14:944–950. doi: 10.1111/j.1463-1326.2012.01638.x.
    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. 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. Vora J, Christensen T, Rana A, Bain SC. Insulin degludec versus insulin glargine in type 1 and type 2 diabetes mellitus: a meta-analysis of endpoints in phase 3a trials. Diabetes Ther. 2014;5:435–446. doi: 10.1007/s13300-014-0076-9.
    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. 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. Davies M, Sasaki T, Gross JL, et al. Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial. Diabetes Obes Metab. 2016;18:96–99. doi: 10.1111/dom.12573.
    1. Rosenstock J, Cheng A, Ritzel R, et al. More similarities than differences testing insulin glargine 300 units/mL versus insulin degludec 100 units/mL in insulin-naive type 2 diabetes: the randomized head-to-head BRIGHT trial. Diabetes Care. 2018 doi: 10.2337/dc18-0559.
    1. Philis-Tsimikas A, Klonoff DC, Khunti K, et al. Risk of hypoglycaemia with insulin degludec versus insulin glargine U300 in insulin-treated patients with type 2 diabetes: the randomised, head-to-head CONCLUDE trial. Diabetologia. 2020;63:698–710. doi: 10.1007/s00125-019-05080-9.
    1. Blonde L, Khunti K, Harris SB, Meizinger C, Skolnik NS. Interpretation and impact of real-world clinical data for the practicing clinician. Adv Ther. 2018;35:1763–1774. doi: 10.1007/s12325-018-0805-y.
    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. Fadini GP, Feher M, Hansen TK, et al. 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. Novo Nordisk Canada Inc. Product monograph: TRESIBA® FlexTouch® 100 U/mL, Solution for injection in a pre-filled pen. 2019. . Accessed July 2020.
    1. McGibbon A, Adams L, Ingersoll K, Kader T, Tugwell B. Glycemic management in adults with type 1 diabetes (Diabetes Canada clinical practice guidelines expert committee) Can J Diabetes. 2018;42(Suppl 1):S80–S87. doi: 10.1016/j.jcjd.2017.10.012.
    1. Lipscombe L, Booth G, Butalia S, et al. Pharmacologic glycemic management of type 2 diabetes in adults (Diabetes Canada clinical practice guidelines expert committee) Can J Diabetes. 2018;42(Suppl 1):S88–S103. doi: 10.1016/j.jcjd.2017.10.034.
    1. Crowshoe L, Dannenbaum D, Green M, Henderson R, Hayward MN, Toth E. Type 2 diabetes and indigenous peoples (Diabetes Canada clinical practice guidelines expert committee) Can J Diabetes. 2018;42(Suppl 1):S296–S306. doi: 10.1016/j.jcjd.2017.10.022.
    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. Khunti K, Cigrovski Berkovic M, Ludvik B, et al. Regional variations in definitions and rates of hypoglycaemia: findings from the global HAT observational study of 27 585 people with type 1 and insulin-treated type 2 diabetes mellitus. Diabet Med. 2018;35:1232–1241. doi: 10.1111/dme.13662.
    1. Ratzki-Leewing A, Harris SB, Mequanint S, et al. Real-world crude incidence of hypoglycemia in adults with diabetes: results of the InHypo-DM Study, Canada. BMJ Open Diabetes Res Care. 2018;6:e000503. doi: 10.1136/bmjdrc-2017-000503.
    1. Ostenson CG, Geelhoed-Duijvestijn P, Lahtela J, Weitgasser R, Markert Jensen M, Pedersen-Bjergaard U. Self-reported non-severe hypoglycaemic events in Europe. Diabet Med. 2014;31:92–101. doi: 10.1111/dme.12261.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir