TY - JOUR
T1 - Effects of dapagliflozin on hospitalisations in people with type 2 diabetes
T2 - post-hoc analyses of the DECLARE-TIMI 58 trial
AU - Schechter, Meir
AU - Wiviott, Stephen D.
AU - Raz, Itamar
AU - Goodrich, Erica L.
AU - Rozenberg, Aliza
AU - Yanuv, Ilan
AU - Murphy, Sabina A.
AU - Zelniker, Thomas A.
AU - Fredriksson, Martin
AU - Johansson, Peter A.
AU - Leiter, Lawrence A.
AU - Bhatt, Deepak L.
AU - McGuire, Darren K.
AU - Wilding, John P.H.
AU - Gause-Nilsson, Ingrid A.M.
AU - Cahn, Avivit
AU - Langkilde, Anna Maria
AU - Sabatine, Marc S.
AU - Mosenzon, Ofri
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/4
Y1 - 2023/4
N2 - Background: In people with type 2 diabetes at high risk of cardiovascular or kidney disease, sodium-glucose co-transporter 2 (SGLT2) inhibitors consistently reduce the risk of hospitalisations for heart failure. Less is known about their effects on hospitalisation from any cause, especially in people with type 2 diabetes without atherosclerotic cardiovascular disease, which includes most of the global population of people with type 2 diabetes. We aimed to assess the effect of the SGLT2 inhibitor, dapagliflozin, on the risks of hospitalisations for any cause and for specific causes in people with type 2 diabetes with and without atherosclerotic cardiovascular disease. Methods: The DECLARE-TIMI 58 trial was a double-blind, multicentre, randomised, placebo-controlled study. People with type 2 diabetes and either risk factors for or established atherosclerotic cardiovascular disease were randomly assigned (1:1) to receive oral dapagliflozin 10 mg or placebo once daily. In these post-hoc analyses, the effects of dapagliflozin on risks of first non-elective any-cause and cause-specific hospitalisation were assessed with Cox proportional hazards regression models overall and in the subset of participants without prevalent atherosclerotic cardiovascular disease. The risk of total (first plus subsequent) non-elective hospitalisations was assessed with Lin-Wei-Ying-Yang model. Investigator-reported System Organ Class terms were used to classify cause-specific hospitalisations. The trial is registered with ClinicalTrials.gov, NCT01730534. Findings: Between April 25, 2013, and Sept 18, 2018, 17 160 people (6422 [37·4%] women, 10 738 [62·6%] men; mean age 63·9 years [SD 6·8]) were enrolled in the original trial, of whom 10186 (59·4%) had multiple risk factors for but did not have established atherosclerotic cardiovascular disease, and 6835 (39·8%) had both no evidence of atherosclerotic cardiovascular disease and low KDIGO risk. Over a median follow-up of 4·2 years (IQR 3·9–4·4), dapagliflozin was associated with a lower risk of first non-elective hospitalisation for any cause (2779 [32·4%] of 8582 people in the dapagliflozin group vs 3036 [35·4%] of 8578 people in the placebo group; hazard ratio [HR] 0·89 [95% CI 0·85–0·94]) and total (first plus subsequent) non-elective hospitalisations for any cause (risk ratio 0·92 [95% CI 0·86–0·97]). The association between dapagliflozin use and the risk of first non-elective hospitalisation for any cause was consistent in subgroups of participants with (HR 0·92 [95% CI 0·85–0·99] and without (0·87 [0·81–0·94]) atherosclerotic cardiovascular disease at baseline (p interaction=0·31). Compared with the placebo group, the dapagliflozin group had lower risk of first hospitalisations due to cardiac disorders (HR 0·91 [95% CI 0·84–1·00]), metabolism and nutrition disorders (0·73 [0·60–0·89]), renal and urinary disorders (0·61 [0·49–0·77]), and due to any other cause excluding these three causes (0·90 [0·85–0·96]). Treatment with dapagliflozin was also associated with a lower risk of hospitalisations due to musculoskeletal and connective tissue disorders (HR 0·81 [0·67–0·99]) and infections and infastations (HR 0·86 [0·78–0·96]). Interpretation: Dapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. Funding: AstraZeneca.
AB - Background: In people with type 2 diabetes at high risk of cardiovascular or kidney disease, sodium-glucose co-transporter 2 (SGLT2) inhibitors consistently reduce the risk of hospitalisations for heart failure. Less is known about their effects on hospitalisation from any cause, especially in people with type 2 diabetes without atherosclerotic cardiovascular disease, which includes most of the global population of people with type 2 diabetes. We aimed to assess the effect of the SGLT2 inhibitor, dapagliflozin, on the risks of hospitalisations for any cause and for specific causes in people with type 2 diabetes with and without atherosclerotic cardiovascular disease. Methods: The DECLARE-TIMI 58 trial was a double-blind, multicentre, randomised, placebo-controlled study. People with type 2 diabetes and either risk factors for or established atherosclerotic cardiovascular disease were randomly assigned (1:1) to receive oral dapagliflozin 10 mg or placebo once daily. In these post-hoc analyses, the effects of dapagliflozin on risks of first non-elective any-cause and cause-specific hospitalisation were assessed with Cox proportional hazards regression models overall and in the subset of participants without prevalent atherosclerotic cardiovascular disease. The risk of total (first plus subsequent) non-elective hospitalisations was assessed with Lin-Wei-Ying-Yang model. Investigator-reported System Organ Class terms were used to classify cause-specific hospitalisations. The trial is registered with ClinicalTrials.gov, NCT01730534. Findings: Between April 25, 2013, and Sept 18, 2018, 17 160 people (6422 [37·4%] women, 10 738 [62·6%] men; mean age 63·9 years [SD 6·8]) were enrolled in the original trial, of whom 10186 (59·4%) had multiple risk factors for but did not have established atherosclerotic cardiovascular disease, and 6835 (39·8%) had both no evidence of atherosclerotic cardiovascular disease and low KDIGO risk. Over a median follow-up of 4·2 years (IQR 3·9–4·4), dapagliflozin was associated with a lower risk of first non-elective hospitalisation for any cause (2779 [32·4%] of 8582 people in the dapagliflozin group vs 3036 [35·4%] of 8578 people in the placebo group; hazard ratio [HR] 0·89 [95% CI 0·85–0·94]) and total (first plus subsequent) non-elective hospitalisations for any cause (risk ratio 0·92 [95% CI 0·86–0·97]). The association between dapagliflozin use and the risk of first non-elective hospitalisation for any cause was consistent in subgroups of participants with (HR 0·92 [95% CI 0·85–0·99] and without (0·87 [0·81–0·94]) atherosclerotic cardiovascular disease at baseline (p interaction=0·31). Compared with the placebo group, the dapagliflozin group had lower risk of first hospitalisations due to cardiac disorders (HR 0·91 [95% CI 0·84–1·00]), metabolism and nutrition disorders (0·73 [0·60–0·89]), renal and urinary disorders (0·61 [0·49–0·77]), and due to any other cause excluding these three causes (0·90 [0·85–0·96]). Treatment with dapagliflozin was also associated with a lower risk of hospitalisations due to musculoskeletal and connective tissue disorders (HR 0·81 [0·67–0·99]) and infections and infastations (HR 0·86 [0·78–0·96]). Interpretation: Dapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. Funding: AstraZeneca.
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U2 - 10.1016/S2213-8587(23)00009-8
DO - 10.1016/S2213-8587(23)00009-8
M3 - Article
C2 - 36878239
AN - SCOPUS:85150381753
SN - 2213-8587
VL - 11
SP - 233
EP - 241
JO - The Lancet Diabetes and Endocrinology
JF - The Lancet Diabetes and Endocrinology
IS - 4
ER -