SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis

Abstract

Importance: The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported.

Objective: To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF.

Data sources: The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023.

Study selection: Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included.

Data extraction and synthesis: Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted.

Main outcomes and measures: Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS).

Results: In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes.

Conclusions and relevance: These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

Figure 1.. Flow Diagram for Study Identification and Inclusion

KCCQ-12 indicates Kansas City Cardiomyopathy Questionnaire-12; MLHFQ, Minnesota Living with Heart Failure Questionnaire; SGLT2i, Sodium glucose cotransporter-2 inhibitor; VO₂, oxygen uptake.

Figure 2.. Association of SGLT2i Treatment With Peak Oxygen Consumption

Peak oxygen consumption (VO₂) was measured as milliliters per kilogram per minute. MD indicates mean difference; SGLT2i, sodium glucose cotransporter-2 inhibitor.

Figure 3.. Association of SGLT2i Treatment With 6-Minute Walk Distance

The 6-minute walk distance was measured in meters. MD indicates mean difference; SGLT2i, sodium glucose cotransporter-2 inhibitor.

Figure 4.. Association of SGLT2i Treatment With Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) Outcomes

CSS indicates clinical summary score; MD, mean difference; OSS, overall summary score; SGLT2i, sodium glucose cotransporter-2 inhibitor; TSS; total summary score.