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Treatment intensification strategies after initial metformin therapy in adult patients with type-2 diabetes: results of the DPV and DIVE registries

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Abstract

Aims

Our study aimed to analyse treatment strategies after failure of initial metformin mono-therapy in adult patients with type-2 diabetes (T2DM).

Methods

The DIVE and DPV databases were combined and 16,681 adult patients with T2DM and metformin mono-therapy identified. Patients were analysed depending on whether metformin was continued (MET), or whether it was combined with other oral antidiabetics (OAD), with GLP-1 antagonists (GLP-1) or with basal insulin (BOT/BOT plus). Metabolic control, body weight and hypoglycaemia, micro- and macro-vascular events were compared within 1 year.

Results

A total of 11,911 (71%) participants continued MET until the end of the observation period, 3334 (20.0%) were intensified using OAD, 579 (3%) started on GLP-1, and 857 (5%) were initiated on BOT/BOTplus. Predictors of OAD and BOT/BOTplus therapy were elevated HbA1c, longer diabetes duration and the presence of micro- and macro-vascular diseases, while GLP-1 therapy was predicted by younger age, female sex, higher body weight and shorter diabetes duration. Micro- and macro-vascular diseases were negative predictors of GLP-1 therapy. Effects on HbA1c were highest in the BOT/BOTplus and OAD group, while GLP-1 treatment had the best effect on body weight.

Conclusions

BOT/BOTplus and OAD show good HbA1c reduction even in patients with longer diabetes duration and in older patients. GLP-1 therapy is effective concerning weight loss in overweight patients and is more often used in females and patients with shorter diabetes duration. Interestingly, despite several studies showing positive effects on micro- and macro-vascular outcomes, prevalent macro-vascular diseases are no predictors of GLP-1 use.

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Acknowledgements

We thank all participating centres of the DPV and DIVE initiatives, especially those who collaborated in this investigation.

Funding

The DPV registry was supported by the European Foundation for the Study of Diabetes (EFSD). Further financial support was provided by the German Diabetes Society (DDG) and the German Centre for Diabetes Research (DZD). The DIVE registry received funding from Sanofi, AstraZeneca, Bayer and Abbott. Funders were not involved in study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the article for publication.

Author information

Author notes

  1. Reinhard W. Holl and Peter Bramlage shared senior authorship.

Authors and Affiliations

  1. Heilig-Geist Hospital Bensheim, Abteilung für Gastroenterologie und Diabetologie, Rodensteinstrasse 94, 64625, Bensheim, Germany

    Bettina Hartmann

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

    Stefanie Lanzinger & Reinhard W. Holl

  3. Deutsches Zentrum für Diabetesforschung e.V, Munich, Neuherberg, Germany

    Stefanie Lanzinger & Reinhard W. Holl

  4. Institut für Pharmakologie und Präventive Medizin, Cloppenburg, Germany

    Gesine van Mark & Peter Bramlage

  5. Diabetespraxis Wosch, Hanau, Germany

    Frank Jürgen Wosch

  6. Schwerpunktpraxis für Diabetes, Hormone und Stoffwechsel, Hof, Germany

    Mesut Durmaz

  7. Diabetologische Schwerpunktpraxis Hannover, Hannover, Germany

    Maike Plaumann

  8. Patienten Praxis Berlin Tempelhof, Berlin, Germany

    Stefan Sziegoleit

  9. Universitätsklinikum Freiburg, Medizinische Fakultät, Freiburg, Germany

    Jochen Seufert

Authors
  1. Bettina Hartmann
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  2. Stefanie Lanzinger
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  3. Gesine van Mark
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  4. Frank Jürgen Wosch
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  5. Mesut Durmaz
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  6. Maike Plaumann
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  7. Stefan Sziegoleit
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  8. Jochen Seufert
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  9. Reinhard W. Holl
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  10. Peter Bramlage
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Consortia

for the DPV and DIVE registry initiatives

Contributions

FJW, MD, SS and MP collected data and contributed to discussion and finalization of the manuscript. BH, GvM and PB designed the analysis, drafted the manuscript and created figures. SL and RWH did the statistical analyses. SL, FJW, MD, MP, SS, JS and RWH contributed to the discussion and reviewed/edited the manuscript. SL had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors approved the final manuscript submitted.

Corresponding author

Correspondence to Bettina Hartmann.

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Conflict of interest

JS reports grants and personal fees from Abbott, AstraZeneca and Sanofi, outside the submitted work. PB reports to have received consultancy honoraria from Sanofi and Abbott. BH, SL, GvM, FJW, MD, MP and SS have no competing interests to disclose.

Ethical standard

The registry was conducted in accordance with Good Epidemiology Practice and applicable regulatory requirements. The protocol of DIVE registry was approved by the ethics committee of the Medical School of Hannover (approval no. 6003), the protocol of DPV was approved by the ethics committee of the University of Ulm (approval no. 202/09), and data collection was approved by local review board.

Human and animal rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All patients being enrolled into this registry provided written informed consent.

Additional information

Managed by Massimo Porta.

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Hartmann, B., Lanzinger, S., van Mark, G. et al. Treatment intensification strategies after initial metformin therapy in adult patients with type-2 diabetes: results of the DPV and DIVE registries. Acta Diabetol 57, 229–236 (2020). https://doi.org/10.1007/s00592-019-01409-3

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  • DOI: https://doi.org/10.1007/s00592-019-01409-3

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