Preventing all‐cause hospitalizations in type 2 diabetes with sodium‐glucose cotransporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists: A narrative review and proposed clinical approach

Abstract

Patients with type 2 diabetes (T2D) are at increased risk for hospital admissions, and acute hospitalizations are associated with a worse prognosis. However, outcomes related to all-cause hospital admissions (ACHAs) were often overlooked in trials that demonstrated the cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs). This review includes a contemporary literature summary of emerging data regarding the effects of SGLT2 inhibitors and GLP-1RAs on ACHAs. The role of SGLT2 inhibitors in preventing ACHAs was shown in exploratory investigations of several randomized controlled trials (RCTs) and was further supported by real-world evidence (RWE). However, the association between GLP-1RA use and lower ACHA risk was mainly shown through RWE, with minimal available RCT data. We also discuss the advantages and challenges of studying ACHAs. Finally, we propose an easily memorized ("ABCDE" acronym) clinical approach to evaluating T2D status and treatment in admitted patients, as they transition from hospital to community care. This systematic approach may assist clinicians in recognizing possible pitfalls in T2D management, thereby preventing subsequent hospitalizations and improving patient prognoses. While acute admission can sometimes be perceived as a management failure, it should also be viewed as an opportunity to take action to prevent the next hospitalization.

Effects of Dapagliflozin on Hospitalizations in Patients With Chronic Kidney Disease

“…This semiparametric proportional-rates time-gap model considers all hospitalizations or deaths and is therefore more suitable than models that do not count death as an event (16,17). We conducted sensitivity analyses to assess the effect of dapagliflozin compared with placebo on all (first and subsequent) hospitalizations using a joint frailty model (10,16), a Prentice-Williams-Peterson total-time model (18), a Wei-Lin-Weissfeld model (13,18), and a negative binomial model (12,13). We conducted between-group comparisons for all (first and recurrent) hospitalizations by MedDRA system organ class using negative binomial models (12,13).…”

Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial

“…During the DECLARE-TIMI 58 trial's median follow-up of 4 Six other cardiovascular or kidney outcome trials assessed the effect of SGLT1 and SGLT2 inhibitors on any-cause hospitalisation events in different populations: EMPA-REG OUTCOME, 10 EMPA-KIDNEY, 12 DAPA-CKD, 13 EMPEROR-Preserved, 20 SOLOIST-WHF, 11 and the CANVAS trials programme. 4,21 In some analyses, [10][11][12][13]21 SGLT1 and SGLT2 inhibition was shown to reduce the risk of any-cause hospitalisation, 22 but this is not true for all analyses. 4,20 In participants with chronic kidney disease with or without type 2 diabetes (EMPA-KIDNEY 12 and DAPA-CKD 13 ) or with type 2 diabetes and estab lished atherosclerotic cardiovascular disease (EMPA-REG OUTCOME 10 ), SGLT2 inhibitors reduced the risk of first and all non-elective hospitalisations.…”

Risk of hospitalization with sodium‐glucose cotransporter‐2 inhibitors versus dipeptidyl peptidase‐4 inhibitors in patients with type 2 diabetes lacking evidence of chronic kidney disease: Real‐world data

“…These findings are in line with cumulating data from RCTs. [4][5][6][7][8][9][10] In the EMPA-REG OUTCOME trial, treatment with empagliflozin compared with placebo resulted in a significant 11% (95% CI [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] reduction in the risk of first hospitalization in patients with T2D and previous cardiovascular disease. 4 In the CANVAS program, which also included patients with high risk but without established cardiovascular disease, the risk of first all-cause hospitalization was one of the prespecified outcomes.…”

“…Several real-world evidence studies also found an association between SGLT2 inhibitor use and a lower risk of hospitalization. [15][16][17][18] However, these studies had shorter follow-up duration, [15][16][17] fewer participants, 15,16 or high CV risk. 16 The long-term follow-up accompanied by a large number of participants in this analysis enabled us to show that SGLT2 inhibitor use is associated with reduced risk of any-cause hospitalization, even in patients with T2D without evidence of CKD.…”

“…Several real‐world evidence studies also found an association between SGLT2 inhibitor use and a lower risk of hospitalization 15–18 . However, these studies had shorter follow‐up duration, 15–17 fewer participants, 15,16 or high CV risk 16 .…”