Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis.

Martin Martin,Tatsuya Takagi,Yu-Shi Tian,Yi Zhou

doi:10.1007/s00210-021-02128-9

Martin Martin, Tatsuya Takagi + Show 2 more

Open Access

https://doi.org/10.1007/s00210-021-02128-9

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Abstract

We aimedto assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12weeks of follow-up comparing efficacy (HbA1c) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty.Eighteen RCTs (≥ 24weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA1c reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty).In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during ≥ 24weeks of follow-upin T1D adults.

Highlights

Type 1 diabetes (T1D) is characterized by insulin deficiency and resultant hyperglycemia (DiMeglio et al 2018)
Systematical comparisons on the efficacy or safety between first-generation basal insulins vs. neutral protamine Hagedorn (NPH) have been discussed in an umbrella review (Laranjeira et al 2018)
Sensitivity analysis showed this result is consistent in follow-up durations from either ≥ 24 weeks or ≥ 12 weeks. This result of efficacy is consistent with Bain et al (2020) that concluded no significant differences among insulin analogs in T1D adults (Bain et al 2020). This result is inconsistent with another network meta-analysis (Tricco et al 2021) that showed second-generation basal insulin degludec was superior to NPH in reducing HbA1c

Summary

Introduction

Type 1 diabetes (T1D) is characterized by insulin deficiency and resultant hyperglycemia (DiMeglio et al 2018). The most recent updated network metaanalysis comparing NPH and detemir with the second-generation basal insulins in T1D adults indicated similar reductions in HbA1c and severe hypoglycemic events (Bain et al 2020). Their network meta-analysis on safety only concerned with severe hypoglycemia, defined as the most dangerous level (level one) by American Diabetes Association (ADA) (International Hypoglycaemia Study Group 2017). The confirmed hypoglycemia occurring at night is dangerous and should be aware In their outcome of severe hypoglycemia, only the number of events per person-year was updated. A more comprehensive analysis of the efficacy and safety of second-generation basal insulins is still necessary

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