A review of the NG17 recommendations for the use of basal insulin in type 1 diabetes

Abstract

Aims: To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).

Methods: We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.

Results: The absolute changes in HbA_1c were similar to those reported in the NG17. However, all 95% credible intervals for change in HbA_1c point estimates crossed the line of null effect, except for detemir twice daily (in the NICE and extended 2017 NMAs) and NPH four times daily. In the detemir twice-daily centred post hoc analysis, the 95% credible intervals for change in HbA_1c crossed the line of null effect for all basal therapies, except NPH.

Conclusions: In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA_1c . In the NMAs, statistical significance was severely undermined by the wide credible intervals. Despite these limitations, point estimates of HbA_1c were used to rank the insulins and formed the basis of NG17 guidance. This study queries whether such analyses should be used to make specific clinical recommendations.

Figure 1

PRISMA flow diagram.

Figure 2

Extended network meta‐analysis (NMA) 2017: change in (a) HbA_1c and (b) severe/major hypoglycaemia relative to neutral protamine Hagedorn (NPH) twice daily. Note: the extended NMA 2017 included randomized controlled trails (RCTs) up to 2017 including insulin glargine 300 U/ml. *Differences were calculated from the median of the posterior distribution for the mean change or mean rate change from the NMA. †Person‐years of exposure were calculated as the number of enrolled participants multiplied by the intended follow‐up time in years for each study to ensure consistency between RCTs; however, this ignores participant dropout rates. For the hypoglycaemia endpoint, NPH four times daily was not included as a network could not be formed with this basal insulin regimen.

Figure 3

Restricted network meta‐analysis (NMA) 2017: change in HbA_1c relative to neutral protamine Hagedorn (NPH) twice daily. Note: The restricted NMA 2017 included randomized controlled trials (up to 2017 including insulin glargine 300 U/ml) with > 100 participants and a follow‐up of ≥ 6 months. *NPH twice daily (the reference in the NICE NG17 guideline) and insulin detemir twice daily could not be included in the hypoglycaemia network; therefore, comparisons could not be calculated. Differences were calculated from the median of the posterior distribution for the mean change from the NMA.

Figure 4

Twice‐daily insulin detemir‐centred network meta‐analysis (NMA): change in HbA_1c relative to insulin detemir twice daily for the 2017 extended data set. Note: The 2017 extended data set included randomized controlled trials up to 2017 including insulin glargine 300 U/ml. *Differences were calculated from the median of the posterior distribution for the mean change from the NMA.

Figure 5

Twice‐daily insulin detemir‐centred network meta‐analysis (NMA): change in HbA_1c relative to insulin detemir twice daily for the 2017 restricted data set. Note: The 2017 restricted data set included randomized controlled trials (up to 2017 including insulin glargine 300 U/ml) with > 100 participants and a follow‐up of ≥ 6 months. *Differences were calculated from the median of the posterior distribution for the mean change from the NMA.