Skip to main content
SpringerLink
Log in

Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study

  • Short Communication
  • Published:
Diabetologia Aims and scope Submit manuscript

Abstract

Aims/hypothesis

The aim of this study was to compare the performance of the second-generation basal insulins, insulin degludec 100 U/ml (Deg-100) and insulin glargine 300 U/ml (Gla-300), in terms of change in HbA1c, hospitalisation for hypoglycaemia and all-cause mortality among individuals with type 2 diabetes and concurrent chronic kidney disease.

Methods

This register-based cohort study, based on the entire Danish diabetes population, included 6519 new users of Deg-100 and Gla-300 with type 2 diabetes and moderate to end-stage chronic kidney disease. HbA1c trajectories, from initiation of either Deg-100 (2013) or Gla-300 (2015) to end of follow-up (2020), were modelled with mixed-effect models while rates of hospitalisation for hypoglycaemia and all-cause mortality were modelled in separate models using Poisson likelihood.

Results

Of the 6519 (44% women) individuals included in the study, 3747 were exposed to Deg-100 and 2772 to Gla-300. Both mean (SD) type 2 diabetes duration (14.4 [6.6] years vs 15.2 [6.7] years) and median (IQR) chronic kidney disease duration (2.3 [1.3, 3.9] years vs 2.8 [1.6, 4.6] years) were significantly shorter in the Gla-300 group. The median (IQR) follow-up time was similar between groups: 1.0 (0.5–1.6) year for Gla-300 and 1.0 (0.3–1.5) year for Deg-100. In both groups mean HbA1c levels were reduced by 13–14 mmol/mol (1.2–1.3%) from initiation to end of follow-up, with the largest reduction (of 8–9 mmol/mol [0.7–0.8%]) occurring during the first year. There was no significant difference in HbA1c reduction between Deg-100 and Gla-300. Both the rate of hospitalisation for hypoglycaemia (rate ratio 1.02 [95% CI 0.70, 1.49], Deg-100 vs Gla-300) and the rate of all-cause mortality (rate ratio 0.98 [95% CI 0.84, 1.15], Deg-100 vs Gla-300) were similar between the groups.

Conclusions/interpretation

We found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Abbreviations

BIA:

Basal insulin analogues

CKD:

Chronic kidney disease

Deg-100:

Insulin degludec u100

DNPR:

Danish National Prescription Registry

Gla-300:

Insulin glargine u300

HH:

Hospitalisation for hypoglycaemia

References

  1. New JP, Middleton RJ, Klebe B et al (2007) Assessing the prevalence, monitoring and management of chronic kidney disease in patients with diabetes compared with those without diabetes in general practice. Diabet Med J Br Diabet Assoc 24(4):364–369. https://doi.org/10.1111/j.1464-5491.2007.02075.x

    Article  CAS  Google Scholar 

  2. MacIsaac RJ, Jerums G, Ekinci EI (2017) Effects of glycaemic management on diabetic kidney disease. World J Diabetes 8(5):172–186. https://doi.org/10.4239/wjd.v8.i5.172

    Article  PubMed  PubMed Central  Google Scholar 

  3. Malik AH, Yandrapalli S, Aronow WS et al (2020) Severe hypoglycemia and risk of subsequent cardiovascular events: systematic review and meta-analysis of randomized controlled trials. Cardiol Rev 28(5):244–249. https://doi.org/10.1097/crd.0000000000000276

    Article  PubMed  Google Scholar 

  4. ElSayed NA, Aleppo G, Aroda VR et al (2022) 9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2023. Diabetes Care 46(Supplement_1):S140–S157. https://doi.org/10.2337/dc23-S009

    Article  PubMed Central  Google Scholar 

  5. Haluzík M, Cheng A, Müller-Wieland D et al (2020) Differential glycaemic control with basal insulin glargine 300 U/mL versus degludec 100 U/mL according to kidney function in type 2 diabetes: a subanalysis from the BRIGHT trial. Diabetes Obes Metab 22(8):1369–1377. https://doi.org/10.1111/dom.14043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Philis-Tsimikas A, Klonoff DC, Khunti K et al (2020) Risk of hypoglycaemia with insulin degludec versus insulin glargine U300 in insulin-treated patients with type 2 diabetes: the randomised, head-to-head CONCLUDE trial. Diabetologia 63(4):698–710. https://doi.org/10.1007/s00125-019-05080-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pieber TR, Bajaj HS, Heller SR et al (2022) Impact of kidney function on the safety and efficacy of insulin degludec versus insulin glargine U300 in people with type 2 diabetes: a post hoc analysis of the CONCLUDE trial. Diabetes Obes Metab 24(2):332–336. https://doi.org/10.1111/dom.14564

    Article  CAS  PubMed  Google Scholar 

  8. Sullivan SD, Bailey TS, Roussel R et al (2018) Clinical outcomes in real-world patients with type 2 diabetes switching from first- to second-generation basal insulin analogues: comparative effectiveness of insulin glargine 300 units/mL and insulin degludec in the DELIVER D+ cohort study. Diabetes Obes Metab 20(9):2148–2158. https://doi.org/10.1111/dom.13345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pettus J, Roussel R, Liz Zhou F et al (2019) Rates of hypoglycemia predicted in patients with type 2 diabetes on insulin glargine 300 U/ml versus first- and second-generation basal insulin analogs: the Real-World LIGHTNING study. Diabetes Ther Res Treat Educ Diabetes Relat Disord 10(2):617–633. https://doi.org/10.1007/s13300-019-0568-8

    Article  CAS  Google Scholar 

  10. Kawaguchi Y, Sawa J, Hamai C, Kumeda Y (2019) Differential effect of hypoalbuminemia on hypoglycemia on type 2 diabetes patients treated with insulin glargine 300 U/ml and insulin degludec. Diabetes Ther Res Treat Educ Diabetes Relat Disord 10(4):1535–1541. https://doi.org/10.1007/s13300-019-0654-y

    Article  CAS  Google Scholar 

  11. (2019) Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol 7(5):385–396. https://doi.org/10.1016/s2213-8587(18)30315-2

  12. Cea Soriano L, Johansson S, Stefansson B, Rodríguez LA (2015) Cardiovascular events and all-cause mortality in a cohort of 57,946 patients with type 2 diabetes: associations with renal function and cardiovascular risk factors. Cardiovasc Diabetol 14:38. https://doi.org/10.1186/s12933-015-0204-5

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Steno Diabetes Center Copenhagen, Herlev, Denmark

    Vanja Kosjerina, Bendix Carstensen, Hanan Amadid & Dorte Vistisen

  2. Department of Endocrinology, University Hospital Bispebjerg-Frederiksberg, Copenhagen, Denmark

    Vanja Kosjerina

Authors
  1. Vanja Kosjerina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bendix Carstensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hanan Amadid
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dorte Vistisen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vanja Kosjerina.

Ethics declarations

Acknowledgements

We are grateful to the Danish Clinical Registries (RKKP) for providing access to the Danish Adult Diabetes Registry and Database for Screening of Diabetic Retinopathy and Maculopathy, which were used for the construction of the diabetes register.

Data availability

According to Danish law, ethics approvals are not required for registry-based studies. Access and use of the described data were approved by the Danish Data Protection Agency (j-No. VD-2019-197) and the Danish Patient Safety Authority (j-No. 3-3013-2959/1). Data are not publicly available, but access is granted on approval from the different sources.

Funding

This work was supported by Sanofi-Aventis

Authors’ relationships and activities

BC, HA and DV own shares in Novo Nordisk. DV has received research grants from Bayer, Sanofi-Aventis, Novo Nordisk and Boehringer Ingelheim. HA is currently employed by Novo Nordisk. VK declares that there are no relationships or activities that might bias, or be perceived to bias, their work.

Contribution statement

VK, BC, HA and DV were involved in the conception, design and conduct of the study and the analysis and interpretation of the results. VK wrote the first draft of the manuscript and all authors edited, reviewed and approved the final version. VK, HA and BC are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The authors declare that the results of the study are presented clearly, honestly and without fabrication, falsification or inappropriate data manipulation.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 607 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kosjerina, V., Carstensen, B., Amadid, H. et al. Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study. Diabetologia 66, 1908–1913 (2023). https://doi.org/10.1007/s00125-023-05971-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00125-023-05971-y

Keywords

Search

Navigation