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SGLT2i as fourth-line therapy and risk of mortality, end-stage renal diseases and cardiovascular diseases in patients with type 2 diabetes mellitus - 12/08/21

Doi : 10.1016/j.diabet.2020.09.005 
C.K.H. Wong a, b, , E.H.M. Tang a, K.K.C. Man c, d, E.W.Y. Chan c, I.C.K. Wong c, d, C.L.K. Lam a
a Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China 
b Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China 
c Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China 
d Research Department of Policy and Practice, University College London School of Pharmacy, London, UK 

Corresponding author at: Department of Family Medicine and Primary Care / Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Rm 1-01, 1/F, Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong, China.Department of Family Medicine and Primary Care / Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong KongRm 1-01, 1/F, Jockey Club Building for Interdisciplinary Research, 5 Sassoon RoadPokfulamHong Kong, China

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Abstract

Aim

Current guideline recommends insulin as fourth-line glucose-lowering medications. However, treatment effects of sodium glucose co-transporter-2 inhibitors (SGLT2i) on the risk of complications are uncertain. This study examines risks of all-cause mortality, cardiovascular diseases (CVD) and end-stage renal diseases (ESRD) in type 2 diabetes mellitus (T2DM) patients on triple oral glucose-lowering medications initiating SGLT2i, insulin or other oral medications.

Methods

A population-based retrospective cohort of patients with T2DM between 2006–2017 was extracted from Hong Kong Hospital Authority database. Patients who were initiated a fourth-line therapy with SGLT2i, insulin or other oral medications were included. Hazard ratios (HRs) for all-cause mortality, CVD and ESRD were assessed using Cox proportional hazard models.

Results

Over a median follow-up period of 18.5 months with 63,122 person-years, SGLT2i and insulin group had the lowest and highest incidence rate of all-cause mortality, CVD and ESRD (1.06, 0.65 and 0.61 vs 4.25, 5.58 and 4.39/100 person-years), respectively. Initiating SGLT2i as fourth-line medication had more benefits on CVD, in particular coronary heart disease and stroke. Insulin users had higher risks of CVD (HR=8.04, 95%CI=3.06–21.12) than SGLT2i users. SGLT2i was associated with insignificant reduction in ESRD (HR=4.62, 95%CI=0.73–29.09) and all-cause mortality (HR=3.06, 95%CI=0.75–12.45), and HF (HR=2.99, 95%CI=0.37–24.42) among patients without established HF.

Conclusion

Among T2DM patients initiating fourth-line therapy, SGLT2i users had significant benefits in lowering risk of CVD, and potential benefits in lowering risks of ESRD and all-cause mortality. SGLT2i was the preferred fourth-line glucose-lowering medication least likely to be associated with complication risks.

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Keywords : Anti-diabetic drug, Cardiovascular disease, Diabetes complication, Insulin therapy, SGLT2 inhibitor, Type 2 diabetes


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Vol 47 - N° 4

Article 101196- juillet 2021 Retour au numéro
Article précédent Article précédent
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