Sodium-Glucose Cotransporter 2 Inhibitor Effects on Heart Failure Hospitalization and Cardiac Function: Systematic Review

Figures

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  Figure 1. Evolution of SGLTi clinical trials over time. Only studies in patients with T2DM, HF, CVD, or CKD are included. We excluded phase 1 trials and studies assessing PK or safety only. Outcomes being assessed (KEY) by each study were broadly categorized according to the reported primary outcome for each trial. CVD trials include patients with or at risk of CVD. Major trials including assessments of HF‐event outcomes are numbered and described briefly in the appended table. CKD, chronic kidney disease; CVD, cardiovascular disease; HF, heart failure; T2DM, type 2 diabetes mellitus.

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  Figure 2. PRISMA flow diagram summarizing the search strategy. aPhase 1 trials and studies assessing PK and/or safety only were excluded. bIncludes two studies also included in Table 1 (i.e. HHF: double‐blind, placebo‐controlled RCTs). Hence, the total number of studies across categories adds up to 67 rather than 65. AHF, acute heart failure; CF, cardiac failure; CHF, congestive heart failure; CV, cardiovascular; CVD, cardiovascular disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HHF, hospitalization for heart failure; MESH, Medical Subject Headings; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta‐Analyses; RCT, randomized controlled trial; SGLT2, sodium–glucose cotransporter 2; SGLT2i, sodium–glucose cotransporter 2 inhibitor.

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  Figure 3. (A) Potential cardiorenal protective mechanisms that have been proposed to contribute to benefits observed with SGLT2is in patients with HF. (B) Potential mechanisms that may account for early vs. later benefits observed with SGLT2is in patients with HF (adapted from McMurray et al. 8 ). Copyright © (2019) Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society). AMPK, adenosine monophosphate‐activated protein kinase; HF, heart failure; HHF, hospitalization for heart failure; NHE, sodium‐hydrogen exchanger; RAAS, renin–angiotensin–aldosterone system; SGLT2i, sodium–glucose cotransporter 2 inhibitor; SIRT1, sirtuin 1.