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A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes

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Abstract

Aims

(1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA).

Methods

The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration.

Results

Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2 years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4 years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64 mmol/mol versus 7.96%, 63 mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI − 0.08, 0.25)]. FBG was 9.37 mmol/L (168.9 mg/dL) and 9.58 mmol/L (172.6 mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. − 0.21; (95%CI − 1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI − 1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant.

Conclusions

Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.

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Availability of data and material

The datasets generated and analyzed during the current study are not publicly available due to data privacy but are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all participating centers of the Diabetes-Patienten-Verlaufsdokumentation initiative.

Funding

The DPV initiative is supported through the German Center for Diabetes Research (DZD), the German Diabetes Association (DDG), the Robert-Koch-Institute (RKI Berlin), and the Federal Ministry of Education and Research (FKZ 82DZD14A02). This work received additional funding from Sanofi Germany and Abbott Germany. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author information

Authors and Affiliations

  1. Institut für Pharmakologie und Präventive Medizin, Bahnhofstrasse 20, 49661, Cloppenburg, Germany

    Peter Bramlage

  2. Institut für Epidemiologie und Medizinische Biometrie, ZIBMT, Universität Ulm, Ulm, Germany

    Sascha R. Tittel & Stefanie Lanzinger

  3. German Center for Diabetes Research (DZD), Neuherberg, Germany

    Sascha R. Tittel & Stefanie Lanzinger

  4. Diabetes Zentrum für Kinder und Jugendliche, DRK Kliniken Berlin, Berlin, Germany

    Silvia Müther

  5. Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria

    Birgit Reinhart-Steininger

  6. Kinderendokrinologische Ambulanz, Diabeteszentrum für Kinder und Jugendliche, Sozialpädiatrisches Zentrum, Sana Kliniken Berlin-Brandenburg GmbH, Berlin, Germany

    Holger Haberland

  7. Klinikum Hanau, Hanau, Germany

    Semik Khodaverdi

  8. Helios Klinikum Schwerin, Schwerin, Germany

    Stefan Zimny

  9. Altonaer Kinderkrankenhaus, Hamburg, Germany

    Ute Ohlenschläger

  10. Diabetes Zentrum Mergentheim, Bad Mergentheim, Germany

    Thomas Haak

Authors
  1. Peter Bramlage
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Contributions

SRT and SL performed the statistical analysis, PB wrote the first draft of the manuscript, and TH, SM, BRS, and HH recruited patients. All revised the manuscript for important intellectual content and agreed to publish the final version.

Corresponding author

Correspondence to Peter Bramlage.

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Conflict of interest

PB reports to have received consultancy honoraria from Sanofi and Abbott. TH reports to have received consultancy honoraria from Novo Nordisk, Lilly, Sanofi, MSD, Abbott, Boehringer Ingelheim, Dexcom, and Bayer. The other authors declare that they have no conflict of interest.

Ethical approval

The DPV initiative, which was established in 1995, was approved by the ethics committee of the University of Ulm, and data collection was approved by local review boards.

Informed consent

Informed consent was obtained from all participants before enrollment.

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Bramlage, P., Tittel, S.R., Müther, S. et al. A comparison of the rapid-acting insulin analogue glulisine with lispro and aspart for the pump treatment of patients with type 1 diabetes. Acta Diabetol 59, 1453–1460 (2022). https://doi.org/10.1007/s00592-022-01939-3

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