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Dapagliflozin for inpatient hyperglycemia in cardiac surgery patients with type 2 diabetes: randomised controlled trial (Dapa-Hospital trial)

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Abstract

Aims

To examine the efficacy and safety of dapagliflozin in the treatment of hyperglycemia in cardiac surgery patients with type 2 diabetes (T2D).

Methods

Cardiac surgery patients with T2D (n = 250) were randomly assigned (1:1) to receive dapagliflozin plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean difference in daily blood glucose (BG) concentrations between groups. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle.

Results

The median age of the patients was 61 years (range, 55–61), and 219 (87.6%) were men. Overall, the randomization blood glucose was 165 mg/dL (SD, 37) and glycated hemoglobin was 7.7% (SD, 1.4). There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within target BG of 70–180 mg/dL (82.7% vs. 82.5%), total daily insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of hospital stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. The mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but no patient developed DKA. There were no differences in the proportion of patients with BG < 70 mg/dL (9.6% vs. 7.2%) between the two groups.

Conclusion

Dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus insulin alone in hospitalized cardiac surgery patients. Dapagliflozin significantly increases plasma ketones levels. Safety of dapagliflozin in hospitalized patients needs further investigation.

Trial registration ClinicalTrials.gov NCT05457933.

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Data availability

The dataset for the current study is available on reasonable request by contacting MSK.

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Acknowledgements

We want to thank Surender Rao and Manish Kumar (research coordinators, Division of Endocrinology and Diabetes, Medanta-The Medicity Hospital, Gurugram, India) for their help in conducting the study. We also want to thank the Diabetes and Endocrinology Foundation (DEF), India for providing a grant for this study.

Funding

The current study was supported by an investigator-initiated study grant to MSK by the Diabetes and Endocrinology Foundation (DEF), Gurugram, India. The funding agency did not have any role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Division of Endocrinology and Diabetes, Medanta-The Medicity Hospital, Gurugram, Haryana, 122001, India

    Mohammad Shafi Kuchay, Pushpender Khatana, Mitali Mishra, Parjeet Kaur, Jasjeet Singh Wasir, Harmandeep Kaur Gill, Apanshu Singh, Rujul Jain, Chhavi Kohli, Gazal Bakshi, Vishnupriya Radhika, Sumayya Saheer & Sunil Kumar Mishra

  2. ICMR – National Institute of Epidemiology, Ayapakkam, Ambattur, Chennai, Tamil Nadu, 600077, India

    Parvathi Surendran

  3. Department of Clinical Research and Studies, Medanta-The Medicity Hospital, Gurugram, Haryana, 122001, India

    Manish Kumar Singh

Authors
  1. Mohammad Shafi Kuchay
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Contributions

MSK was responsible for the study concept and design, data collection, interpretation of data, drafting of the manuscript, and approval of the final submission. MSK, SKM, PK, MM, AS, CK, and PK contributed to the data collection, insulin dose management, CGM application, and approval of the final submission. MKS and PS contributed to the statistical analysis, critical revision of the manuscript, and approval of the final submission. PK, JSW, HKG, GB, VR, SS and RJ contributed to the data collection, critical revision of the manuscript, and approval of the final submission. MSK is the guarantor of this work and, as such, 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. MSK has received speaker honoraria from Boehringer-Ingelheim, Novartis India, Sanofi, Novo Nordisk, Intas Pharmaceuticals Ltd, Sun Pharmaceutical Industries Ltd, USV Private Limited, and MSD Life Sciences Foundation. PK has received speaker honoraria from Novo Nordisk, Boehringer Ingelheim, and Sanofi. HKG has received speaker and consultant fees from Novo Nordisk and Sanofi. JSW has received speaker honoraria from Abbott India Limited, Novartis, AstraZeneca, and Sanofi. RJ has received speaker honoraria from Sanofi, Novartis, Intas Pharmaceuticals, and Lupin Limited. SKM has received speaker honoraria from Novo Nordisk, Boehringer Ingelheim, Novartis, Sanofi, Lupin Limited and Abbott India Limited.

Corresponding author

Correspondence to Mohammad Shafi Kuchay.

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The study protocol and informed consent form were approved by the Institutional Review Board and the Ethics Committee.

Informed consent

Written informed consent was obtained from all study participants in accordance with the guidelines of the Declaration of Helsinki.

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Kuchay, M.S., Khatana, P., Mishra, M. et al. Dapagliflozin for inpatient hyperglycemia in cardiac surgery patients with type 2 diabetes: randomised controlled trial (Dapa-Hospital trial). Acta Diabetol 60, 1481–1490 (2023). https://doi.org/10.1007/s00592-023-02138-4

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