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. 2021 Oct;23(10):2207-2214.
doi: 10.1111/dom.14437. Epub 2021 Aug 2.

Lower risk of hospitalization for heart failure, kidney disease and death with sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in type 2 diabetes regardless of prior cardiovascular or kidney disease: A retrospective cohort study in UK primary care

Iskandar Idris  1 , Ruiqi Zhang  2   3 , Jil Billy Mamza  3 , Mike Ford  3 , Tamsin Morris  3 , Amitava Banerjee  4   5 , Kamlesh Khunti  6
Affiliations

Lower risk of hospitalization for heart failure, kidney disease and death with sodium-glucose co-transporter-2 inhibitors compared with dipeptidyl peptidase-4 inhibitors in type 2 diabetes regardless of prior cardiovascular or kidney disease: A retrospective cohort study in UK primary care

Iskandar Idris et al. Diabetes Obes Metab. 2021 Oct.

Abstract

Aim: To assess if sodium-glucose co-transporter-2 inhibitors (SGLT2is) reduce the risk of all-cause mortality, cardiovascular death and hospitalization for heart failure (HF) or chronic kidney disease (CKD) to a greater extent than dipeptidyl peptidase-4 inhibitors (DPP4is) in people with type 2 diabetes (T2D) with or without established cardiovascular and/or renal disease (CVRD).

Methods: This retrospective cohort study propensity-matched 24 438 patients receiving an SGLT2i 1:1 to a patient receiving a DDP4i, stratified based on the presence of CVRD. The primary outcomes were the time to each of the following: all-cause mortality, cardiovascular death or hospitalization for HF, myocardial infarction, stroke and CKD.

Results: Overall, SGLT2is were associated with reductions in all-cause mortality, cardiovascular mortality, hospitalization for HF and hospitalization for CKD compared with DPP4is. In patients with no CVRD history, SGLT2is were associated with reductions in all-cause mortality (HR 0.71, 95% CI 0.57-0.88; P = .002), hospitalization for HF (HR 0.76, 95% CI 0.59-0.98; P = .035) and hospitalization for CKD (HR 0.75, 95% CI 0.63-0.88; P < .001). In patients with established cardiovascular disease (CVD) or at high risk, SGLT2is were associated with reductions in all-cause mortality (HR 0.69, 95% CI 0.59-0.82; P < .001), cardiovascular mortality (HR 0.76, 95% CI 0.62-0.95; P = .014), hospitalization for HF (HR 0.73, 95% CI 0.63-0.85; P < .001), hospitalization for stroke (HR 0.75, 95% CI 0.59-0.94; P = .013) and hospitalization for CKD (HR 0.49, 95% CI 0.43-0.54; P < .001).

Conclusion: There was consistency across subgroups and sensitivity analyses. SGLT2is were associated with a reduced risk of all-cause mortality and hospitalization for HF and CKD compared with DPP4-is, highlighting the need to introduce SGLT2is early in the management of patients with T2D.

Keywords: cardiovascular disease; clinical trial; dapagliflozin; diabetes complications; dipeptidyl peptidase-4 inhibitor; heart failure.

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Conflict of interest statement

KK has acted as a consultant, speaker or received grants for investigator‐initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi–Aventis, Lilly and Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin–Chemie AG/Menarini Group, Janssen and Napp. II has acted as an advisory board member, speaker or received grants for Eli Lilly, Novo Nordisk, Merck Sharp & Dohme, AstraZeneca, Abbot Diabetes Care, Sanofi and Boehringer. RZ, JBM, MF and TM are employed by AstraZeneca UK Ltd, a biopharmaceutical company that develops, manufactures and markets medicines in the cardiovascular, renal and metabolic disease area. AB has received research grants from AstraZeneca.

Figures

FIGURE 1
FIGURE 1
Patient disposition. CKD, chronic kidney disease; CVD, cardiovascular disease; CVRD, cardiovascular and/or renal disease; DPP4i, dipeptidyl peptidase‐4 inhibitor; GD, gestational diabetes; HF, heart failure; MI, myocardial infarction; PAD, peripheral artery disease; Rx, prescribed; SGLT2i, sodium‐glucose co‐transporter‐2 inhibitor; TZD, thiazolidinedione; T1D, type 1 diabetes; T2D, type 2 diabetes
FIGURE 2
FIGURE 2
Risk of cardiovascular and renal disease in patients with type 2 diabetes (T2D) without a history of cardiovascular or renal disease and those at high risk of cardiorenal disease (DECLARE‐like). Adjusted Cox regression model with estimates of relative risk reduction. P value is from the test statistic for testing for difference in sodium‐glucose co‐transporter‐2 inhibitors (SGLT2is) versus dipeptidyl peptidase‐4 inhibitors (DPP4is). CKD, chronic kidney disease; CVRD, cardiovascular or renal disease; PY, person years
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References

    1. Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004;27(8):1879‐1884. - PubMed
    1. Parving HH, Lewis JB, Ravid M, Remuzzi G, Hunsicker LG. Prevalence and risk factors formicroalbuminuria in a referred cohort of type II diabetic patients: a global perspective. Kidney Int. 2006;69(11):2057‐2063. - PubMed
    1. Thrainsdottir IS, Aspelund T, Thorgeirsson G, et al. The association between glucose abnormalities and heart failure in the population‐based Reykjavik study. Diabetes Care. 2005;28(3):612‐616. - PubMed
    1. Braunwald E. Diabetes, heart failure, and renal dysfunction: the vicious circles. Prog Cardiovasc Dis. 2019;62(4):298‐302. - PubMed
    1. Taylor CJ, Ordóñez‐Mena JM, Roalfe AK, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000–2017: population based cohort study. BMJ. 2019;364:l223. - PMC - PubMed

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