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Effectiveness of switching from first-generation basal insulin to Glargine 300 U/mL in children and adolescents with type 1 diabetes: results from the ISPED CARD database

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Abstract

Aims

Glargine 300 U/mL (Gla-300) has been recently approved for use in children and adolescents with type 1 diabetes (T1D). However, real-world effectiveness data are scarce, and aim of this analysis was to assess clinical outcomes in young patients with T1D switching from 1st generation basal insulin (1BI) to Gla-300.

Methods

ISPED CARD is a retrospective, multicenter study, based on data anonymously extracted from Electronic Medical Records. The study involved a network of 20 pediatric diabetes centers. Data on all patients aged < 18 years with T1D switching from 1BI to Gla-300 were analyzed to assess clinical characteristics at the switch and changes after 6 and 12 months in glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and standardized body mass index (BMI/SDS). Titration of basal and short-acting insulin doses was also evaluated.

Results

Overall, 200 patients were identified. The mean age at the switch to Gla-300 was 13 years, and mean duration of diabetes was 3.9 years. Average HbA1c levels at switch were 8.8%. After 6 months, HbA1c levels decreased by − 0.88% (95% CI − 1.28; − 0.48; p < 0.0001). The benefit was maintained after 12 months from the switch (mean reduction of HbA1c levels − 0.80%, 95% CI − 1.25; − 0.35, p = 0.0006). Trends of reduction in FBG levels were also evidenced both at 6 months and 12 months. No significant changes in short-acting and basal insulin doses were documented.

Conclusions

The study provides the first real-world evidence of the effectiveness of Gla-300 in children and adolescents with T1D previously treated with 1BI. The benefits in terms of HbA1c levels reduction were substantial, and sustained after 12 months. Additional benefits can be expected by improving the titration of insulin doses.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Qualified researchers may request access to patient-level data and related documents (including, e.g., the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications). Patient-level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants.

Abbreviations

95% CI:

95% Confidence interval

ATC:

Anatomical therapeutic chemical codes

1BI:

First generation basal insulin

2BI:

Second-generation basal insulins

BI:

Basal insulin

BMI:

Body mass index

BMI/SDS:

Standardized BMI

CSII:

Continuous subcutaneous insulin infusion (Insulin Pump)

CGM:

Continuous glucose monitoring

Deg-100:

Degludec 100 U/mL

EMR:

Electronic medical records

FBG:

Fasting blood glucose

Gla-300:

Glargine 300 U/mL

GP:

General practitioner

HbA1c:

Glycated hemoglobin

ISPED CARD:

Italian society of paediatric endocrinology diabetology continuous clinical monitoring of diabetes

LDL:

Low-density lipoproteins

MDI:

Multiple daily injections of insulin

NPH:

Neutral protamine hagedorn insulin

OR:

Odds Ratio

PDOC:

Pediatric diabetes outpatient clinics

RWE:

Real-world evidence

SIEDP:

Italian society of pediatric endocrinology and diabetology

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

T0:

Baseline

T6:

Follow-up at 6 months

T12:

Follow-up at 12 months

QoL:

Quality of life

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Acknowledgements

The authors thank the participating centers and all the collaborators from SANOFI, CORESEARCH and METEDA involved in the study. Additional Assistance: CORESEARCH (Pescara, Italy) was the Clinical Research Organization involved in the data management and statistical analysis (Giuseppe Lucisano, Giusi Graziano), medical writing (Maria Chiara Rossi, Antonio Nicolucci) and regulatory activities (Rosalia Di Lallo, Clara Santavenere) of the study. Meteda (San Benedetto, Italy) developed the software for the data extraction.

The ISPED CARD Study Group: Participating centers—year 2022 (in alphabetic order by town):

 Bracciolini GP, Alessandria; Cherubini V, Ancona ; Bobbio A, Aosta; Zucchini S, Bologna; Suprani T, Cesena; De Donno V, Cuneo; Lombardo F, Messina; Bonfanti R, Milano; Franzese A, Napoli; Rabbone I, Novara; Graziani V, Ravenna; Zampolli M, San Fermo Della Battaglia (CO); Rutigliano I, San Giovanni Rotondo (FG); de Sanctis L, Torino; Guerraggio LP, Tradate (VA); Franceschi R, Trento; Tornese G, Trieste; Franco F, Udine; Maffeis C, Verona; Arnaldi C, Viterbo.

Funding

Statistical analysis and medical writing assistance was funded by Sanofi S.r.l., Milan, Italy.

Author information

Authors and Affiliations

  1. CORESEARCH – Center for Outcomes Research and Clinical Epidemiology, Pescara, Italy

    Maria Chiara Rossi, Giusi Graziano & Antonio Nicolucci

  2. Pediatric Diabetology Unit, Department of Pediatrics, Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy

    Riccardo Bonfanti

  3. Medical Affairs, Sanofi S.R.L., Milan, Italy

    Monica Larosa

  4. Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, Messina, Italy

    Fortunato Lombardo

  5. Meteda Srl, San Benedetto del Tronto, AP, Italy

    Giacomo Vespasiani

  6. Department of Pediatric, IRCCS AOU Bologna, Bologna, Italy

    Stefano Zucchini

  7. Division of Pediatrics, Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy

    Ivana Rabbone

Authors
  1. Maria Chiara Rossi
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  4. Monica Larosa
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Consortia

the ISPED CARD Study Group

  • G. P. Bracciolini
  • , V. Cherubini
  • , A. Bobbio
  • , S. Zucchini
  • , T. Suprani
  • , V. De Donno
  • , F. Lombardo
  • , R. Bonfanti
  • , A. Franzese
  • , I. Rabbone
  • , V. Graziani
  • , M. Zampolli
  • , I. Rutigliano
  • , L. de Sanctis
  • , L. P. Guerraggio
  • , R. Franceschi
  • , G. Tornese
  • , F. Franco
  • , C. Maffeis
  •  & C. Arnaldi

Contributions

All authors made substantial contributions to the conception and design of the work. Riccardo Bonfanti, Fortunato Lombardo, Ivana Rabbone, and Stefano Zucchini contributed to the data collection. Giusi Graziano conducted the statistical analyses. Maria Chiara Rossi and Antonio Nicolucci drafted the article. All authors revised the article critically for important intellectual content. All authors approved the final version to be published. All authors agreed all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Corresponding author

Correspondence to Maria Chiara Rossi.

Ethics declarations

Conflict of interest

Maria Chiara Rossi and Antonio Nicolucci have received funding for research from Sanofi, NovoNordisk, Alfasigma, Pikdare, AstraZeneca, Shionogi, SOBI, and Theras. Riccardo Bonfanti has served on advisory board panels for Sanofi, Novonordisk, Lilly, Medtronic, Abbott, Movi and has received speaker’s fees by Novonordisk, Sanofi, Lilly, Movi, Medtronic, Theras and financial support for research by Movi and Lilly. Giusi Graziano has nothing to disclose. Monica Larosa is an employee of Sanofi and may hold shares and/or stock options in the company. Fortunato Lombardo has received consultancy fees from Movi. Stefano Zucchini has served on advisory board panels for Sanofi and Movi. Giacomo Vespasiani is medical consultant of Meteda. Ivana Rabbone has received honoraria for participating in the speaker bureau and consulting fees as a member of Eli Lilly, Menarini, Medtronic, Theras, Novo Nordisk and Sanofi advisory boards.

Ethical approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008. The study protocol was approved by all local ethics committees of the participating centers.

Informed consent

Due to the study design and the anonymous by design database, based on Italian regulations, the signature of patient informed consent was not requested.

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Rossi, M.C., Bonfanti, R., Graziano, G. et al. Effectiveness of switching from first-generation basal insulin to Glargine 300 U/mL in children and adolescents with type 1 diabetes: results from the ISPED CARD database. Acta Diabetol (2024). https://doi.org/10.1007/s00592-024-02304-2

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