Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr 29;369:m1186.
doi: 10.1136/bmj.m1186.

Use of Sodium-Glucose Co-Transporter 2 Inhibitors and Risk of Serious Renal Events: Scandinavian Cohort Study

Affiliations
Free PMC article

Use of Sodium-Glucose Co-Transporter 2 Inhibitors and Risk of Serious Renal Events: Scandinavian Cohort Study

Björn Pasternak et al. BMJ. .
Free PMC article

Abstract

Objective: To assess the association between use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and risk of serious renal events in data from routine clinical practice.

Design: Cohort study using an active comparator, new user design and nationwide register data.

Setting: Sweden, Denmark, and Norway, 2013-18.

Participants: Cohort of 29 887 new users of SGLT2 inhibitors (follow-up time: dapagliflozin 66.1%; empagliflozin 32.6%; canagliflozin 1.3%) and 29 887 new users of an active comparator, dipeptidyl peptidase-4 inhibitors, matched 1:1 on the basis of a propensity score with 57 variables. Mean follow-up time was 1.7 (SD 1.0) years.

Exposures: SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors, defined by filled prescriptions and analysed according to intention to treat.

Main outcome measures: The main outcome was serious renal events, a composite including renal replacement therapy, death from renal causes, and hospital admission for renal events. Secondary outcomes were the individual components of the main outcome.

Results: The mean age of the study population was 61.3 (SD 10.5) years; 11 108 (19%) had cardiovascular disease, and 1974 (3%) had chronic kidney disease. Use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a reduced risk of serious renal events (2.6 events per 1000 person years versus 6.2 events per 1000 person years; hazard ratio 0.42 (95% confidence interval 0.34 to 0.53); absolute difference -3.6 (-4.4 to -2.8) events per 1000 person years). In secondary outcome analyses, the hazard ratio for use of SGLT2 inhibitors versus dipeptidyl peptidase-4 inhibitors was 0.32 (0.22 to 0.47) for renal replacement therapy, 0.41 (0.32 to 0.52) for hospital admission for renal events, and 0.77 (0.26 to 2.23) for death from renal causes. In sensitivity analyses in each of the Swedish and Danish parts of the cohort, the model was further adjusted for glycated haemoglobin and estimated glomerular filtration rate (Sweden and Denmark) and for blood pressure, body mass index, and smoking (Sweden only); in these analyses, the hazard ratio moved from 0.41 (0.26 to 0.66) to 0.50 (0.31 to 0.81) in Sweden and from 0.42 (0.32 to 0.56) to 0.55 (0.41 to 0.74) in Denmark.

Conclusions: In this analysis using nationwide data from three countries, use of SGLT2 inhibitors, compared with dipeptidyl peptidase-4 inhibitors, was associated with a significantly reduced risk of serious renal events.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work other than those described above; CJ has received personal fees from Pfizer and Bayer outside the submitted work; BE has received personal fees from Amgen, AstraZeneca, Boerhringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Mundipharma, Navamedic, Novo Nordisk, and RLS Global outside the submitted work and grants from Sanofi outside the submitted work; SG has received lecture fees and research grants from AstraZeneca, Boerhringer Ingelheim, Eli Lilly, Merck Sharp and Dohme, Novo Nordisk, and Sanofi outside of the submitted work; AMS has received consulting fees from Celgene and has been employed at IQVIA outside the submitted work.

Figures

Fig 1
Fig 1
Flowchart of patient inclusion in study cohort, Sweden, Denmark, and Norway. DPP4=dipeptidyl peptidase-4; SGLT2=sodium-glucose co-transporter 2. *Patients could be excluded for more than one reason
Fig 2
Fig 2
Cumulative incidence of serious renal events in users of sodium-glucose co-transporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors
Fig 3
Fig 3
Subgroup analyses of serious renal events among users of sodium-glucose co-transporter 2 (SGLT2) inhibitors compared with users of dipeptidyl peptidase-4 (DPP4) inhibitors

Comment in

Similar articles

See all similar articles

References

    1. Thomas MC, Cooper ME, Zimmet P. Changing epidemiology of type 2 diabetes mellitus and associated chronic kidney disease. Nat Rev Nephrol 2016;12:73-81. 10.1038/nrneph.2015.173 - DOI - PubMed
    1. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD, The Collaborative Study Group The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456-62. 10.1056/NEJM199311113292004 - DOI - PubMed
    1. Lewis EJ, Hunsicker LG, Clarke WR, et al. Collaborative Study Group Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-60. 10.1056/NEJMoa011303 - DOI - PubMed
    1. Brenner BM, Cooper ME, de Zeeuw D, et al. RENAAL Study Investigators Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9. 10.1056/NEJMoa011161 - DOI - PubMed
    1. Perkovic V, Jardine MJ, Neal B, et al. CREDENCE Trial Investigators Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 2019;380:2295-306. 10.1056/NEJMoa1811744 - DOI - PubMed

Publication types

MeSH terms

Substances

Feedback