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Clinical Trial
. 2017 Jun;19(6):858-865.
doi: 10.1111/dom.12892. Epub 2017 Mar 3.

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

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Free PMC article
Clinical Trial

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

Stewart B Harris et al. Diabetes Obes Metab. .
Free PMC article

Abstract

Aims: To compare the safety and efficacy of a simpler titration algorithm for insulin degludec/liraglutide (IDegLira) with that used in previous DUAL trials in insulin-naïve patients with type 2 diabetes.

Research design and methods: This 32-week, open-label, non-inferiority trial randomized adults with type 2 diabetes uncontrolled on metformin ± pioglitazone to receive IDegLira, titrated either once weekly, based on the mean of 2 pre-breakfast plasma glucose (PG) readings (n = 210), or twice weekly, based on the mean of 3 pre-breakfast PG readings (n = 210).

Results: Mean HbA1c decreased from 8.2% (65 mmol/mol) to 6.1% (43 mmol/mol) with once-weekly titration and from 8.1% (65 mmol/mol) to 6.0% (42 mmol/mol) with twice-weekly titration; non-inferiority was confirmed (estimated treatment difference: 0.12% [-0.04; 0.28]95%CI , 1.30 mmol/mol [-0.41; 3.01]95%CI ). Approximately 90% of patients achieved HbA1c < 7% in each arm. Mean fasting PG was similar after 32 weeks. Weight change was -1.0 kg vs -2.0 kg for once-weekly vs twice-weekly titration. Rates of severe or blood glucose-confirmed symptomatic hypoglycaemia were low in both arms: 0.16 events/patient-year of exposure (PYE) for once-weekly, 0.76 events/PYE for twice-weekly titration. Mean IDegLira dose at 32 weeks was 41 dose steps (41 U IDeg/1.48 mg Lira) for both arms. Overall adverse event rates were 207.8 and 241.3 events/100 PYE with once-weekly and twice-weekly titration, respectively.

Conclusion: A pragmatic titration algorithm with once-weekly adjustments based on 2 PG readings resulted in a safety and glycaemic efficacy profile similar to that with twice-weekly adjustments based on 3 preceding PG values in insulin-naïve patients.

Trial registration: ClinicalTrials.gov NCT02298192.

Keywords: efficacy; insulin therapy; randomized clinical trials; safety; type 2 diabetes.

Figures

Figure 1
Figure 1
A, HbA1c over time with IDegLira once‐weekly vs twice‐weekly titration. Mean observed values with error bars (standard error mean) based on FAS. Treatment difference analysed using MMRM based on FAS. *Test against non‐inferiority limit of 0.3%. ‐‐‐ ADA/EASD HbA1c target < 7.0%; AACE HbA1c target ≤ 6.5%. B, Change in FPG from baseline. LS Mean values with error bars (standard error mean) based on FAS (IDegLira 1WT/IDegLira 2WT: n = 210/210), using MMRM. C, Daily insulin dose over time. Mean observed values with error bars (standard error mean) based on SAS. D, Body weight over time. Mean observed values with error bars (standard error mean) based on FAS. Treatment difference analysed using MMRM based on FAS. E, Severe or BG‐confirmed symptomatic hypoglycaemia. Mean cumulative function based on SAS (IDegLira 1WT/IDegLira 2WT: n = 209/210). Because of the study design, with more SMPG measurements taken in the 2WT group, the number of hypoglycaemic episodes is expected to be biased towards more hypoglycaemic episodes in the 2WT group compared with the 1WT group. Hence, solely descriptive analysis was applied. The MMRM model included treatment, visit, region and previous OAD treatment as factors, and baseline value as covariate. Interactions between visit and all other factors and the covariate are also included in the model. AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association; BG, blood glucose; EASD, European Association for the Study of Diabetes; ETD, estimated treatment difference; FAS, full analysis set; FPG, fasting plasma glucose; IDegLira, insulin degludec/liraglutide; LS Mean, least square mean; MMRM, mixed model for repeated measurement; OAD, oral antidiabetic drug; SAS, safety analysis set; SMPG, self‐measured plasma glucose; 1WT, once‐weekly titration; 2WT, twice‐weekly titration.

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References

    1. 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). Diabetologia. 2012;55:1577‐1596. - PubMed
    1. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract. 2009;15:540‐559. - PubMed
    1. Khunti S, Davies MJ, Khunti K. Clinical inertia in the management of type 2 diabetes mellitus: a focused literature review. Br J Diabetes Vasc Dis. 2015;15:65‐69.
    1. Kunt T, Snoek FJ. Barriers to insulin initiation and intensification and how to overcome them. Int J Clin Pract. 2009;164:6‐10. - PubMed
    1. Peyrot M, Rubin RR, Lauritzen T, et al, International DAWN Advisory Panel . Resistance to insulin therapy among patients and providers: results of the cross‐national Diabetes Attitudes, Wishes, and Needs study. Diabetes Care. 2005;28:2673‐2679. - PubMed

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