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

A Correction to this article was published on 19 August 2021

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Abstract

We aimed to 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 ≥ 12 weeks 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 (≥ 24 weeks 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 ≥ 24 weeks of follow-up in T1D adults.

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Data availability

The datasets used in this research are published in Supplemental Material (Table S6) which can be found in this published article.

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Abbreviations

ADA:

American Diabetes Association

BHM:

Bayesian hierarchical model

CINeMA:

Confidence in Network Meta-Analysis

CrI:

Credible interval

GRADE:

Grading of Recommendations, Assessment, Development and Evaluation

NICE:

National Institute for Health and Care Excellence

HR:

Hazard ratio

MCMC:

Markov Chain Monte Carlo

MD:

Mean difference

NPH:

Neutral protamine Hagedorn

RR:

Risk ratio

T1D:

Type 1 diabetes

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Acknowledgements

We would like to thank Dr. Mitsuyoshi Takahara (Department of Diabetes Care Medicine, Osaka University Graduate School of Medicine) and Prof. Iichiro Shimomura (Department of Metabolic Medicine, Osaka University Graduate School of Medicine) for their comments.

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Contributions

M conceived and conceptualized the study. M and YZ designed the methodology and contributed to data curation, data analysis, interpretation of the results, discussion, and drafted the manuscript. YST contributed to data analysis and discussion. YST and TT reviewed the manuscript. All authors revised and approved the final manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

Corresponding author

Correspondence to Yu-Shi Tian.

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The authors declare no competing interests.

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Martin and Yi Zhou are first author

Supplementary Information

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Supplementary file1 (1.87 MB)

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Martin, Zhou, Y., Takagi, T. et al. Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis. Naunyn-Schmiedeberg's Arch Pharmacol 394, 2091–2101 (2021). https://doi.org/10.1007/s00210-021-02128-9

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

Keywords

  • Basal insulin
  • Glycemic control
  • Hypoglycemia
  • Weight gain
  • Type 1 diabetes
  • Network meta-analysis