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Effects of Dapagliflozin on Hospitalisations in People With Type 2 Diabetes
TAKE-HOME MESSAGE
- In this exploratory analysis of the DECLARE-TIMI 58 trial, dapagliflozin was associated with a lower risk of first non-elective and total all-cause hospitalisations. Compared with placebo, treatment with dapagliflozin conferred a significantly lower risk of hospitalisations owing to cardiac, kidney, and metabolic causes as well as a 19% and 14% lower risk of hospitalisations owing to musculoskeletal/connective tissue disorders and infections, respectively.
- These findings highlight the wide-ranging benefits of dapagliflozin on all-cause hospitalisation, including those not directly attributed to cardiac/renal/metabolic causes, in patients with type 2 diabetes. These findings may have implications for cumulative health-related quality of life and healthcare-associated costs in this population.
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial
Lancet Diabetes Endocrinol 2023 Mar 03;[EPub Ahead of Print], M Schechter, SD Wiviott, I Raz, EL Goodrich, A Rozenberg, I Yanuv, SA Murphy, TA Zelniker, M Fredriksson, PA Johansson, LA Leiter, DL Bhatt, DK McGuire, JPH Wilding, IAM Gause-Nilsson, A Cahn, AM Langkilde, MS Sabatine, O MosenzonFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
In this new paper, the DECLARE investigators examined all-cause hospitalizations in those with type 2 diabetes randomized to the SGLT2 inhibitor dapagliflozin versus placebo in this cardiovascular outcomes trial, originally published in 2019. While not prespecified, this is an important patient-centered outcome in this population, one where patients with diabetes need hospital admissions more frequently than those without diabetes, often for CVD but also for a variety of other conditions, like infection. The result was an 11% relative risk reduction in first non-elective hospitalizations, which was statistically significant (2779/8582 or 32.4% of individuals in the dapagliflozin group vs 3036/8578 or 35.4% of those in the placebo group; HR, 0.89; 95% CI, 0.85–0.94). Interestingly, several categories of hospitalizations, even those beyond metabolic, cardiovascular, and renal causes, appeared to be reduced by dapagliflozin, including those for musculoskeletal disorders and for infections. The underlying reasons for this impact is not clear, but it is unlikely to be driven through simply improved diabetes control, since the HbA1c levels were not that different between the active therapy and placebo groups (background diabetes therapy could be adjusted in both). We found a similar effect in the EMPA-REG OUTCOME trial,1 so I don’t think these are random or fluke findings. Finally, given the high frequency of hospitalization among patients with diabetes, the number needed to treat with an SGLT2 inhibitor to prevent one hospitalization is much lower than for other outcomes.
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