Saudi Heart Failure Study Reveals SGLT2i Prescribing Gaps

A multicenter retrospective cohort study published in Cardiology and Therapy reveals that sodium–glucose cotransporter-2 inhibitor (SGLT2i) prescription among heart failure patients in Saudi Arabia remains inconsistent despite strong guideline recommendations. The research, conducted across tertiary cardiac centers between January 2016 and December 2024, analyzed real-world data from 1,081 adult patients to characterize utilization patterns and identify clinical factors associated with prescribing decisions. The findings highlight persistent gaps in the adoption of foundational heart failure therapies, with significant variations observed based on patient phenotype, renal function, and comorbidity burden.

SGLT2 inhibitors are now recommended as a core component of guideline-directed medical therapy (GDMT) for patients with heart failure across all ejection fraction categories. Previous randomized controlled trials, including DAPA-HF, EMPEROR-Reduced, DELIVER, and EMPEROR-Preserved, demonstrated that these agents reduce the risk of heart failure hospitalization and cardiovascular death. However, real-world adoption has lagged behind trial evidence, particularly in Middle Eastern health systems where data on prescribing habits has been limited. This study aimed to bridge that gap by examining how SGLT2i use is implemented in routine clinical practice within Saudi Arabia.

The study population included 1,081 adults with an objectively confirmed diagnosis of heart failure, categorized into reduced, mildly reduced, preserved, and improved ejection fraction phenotypes. Of these patients, 626 (57.9%) received an SGLT2 inhibitor during the follow-up period, while 455 (42.1%) did not. The cohort had a median age of 66 years, with 50.8% of participants being women. The inclusion of all ejection fraction phenotypes allowed for a comprehensive assessment of prescribing trends across the full spectrum of heart failure severity and etiology.

Prescribing patterns varied significantly by heart failure phenotype. Utilization was highest among patients with reduced and mildly reduced ejection fraction, whereas uptake was substantially lower in those with preserved ejection fraction. In multivariable analysis, patients with preserved ejection fraction had an adjusted odds ratio of 0.30 for receiving an SGLT2 inhibitor compared to those with reduced ejection fraction. This disparity suggests that clinicians may be more hesitant to initiate therapy in patients with preserved ejection fraction, potentially due to the more recent emergence of trial evidence supporting its use in this specific subgroup compared to reduced ejection fraction.

Renal function emerged as a critical determinant of prescribing decisions. Patients with advanced chronic kidney disease, defined as an estimated glomerular filtration rate below 30 ml/min/1.73 m², were significantly less likely to receive SGLT2 inhibitors. The adjusted odds ratio for prescribing in this group was 0.26, indicating a strong association between severe renal impairment and treatment omission. This finding reflects a common clinical hesitation to prescribe these agents in patients with lower kidney function, despite growing evidence supporting their safety and benefit across a wide range of renal profiles.

Comorbidity status also influenced prescribing behavior. The presence of diabetes mellitus was independently associated with a higher likelihood of SGLT2i use, with an adjusted odds ratio of 2.29. This suggests that the drug class’s origin as a glucose-lowering therapy continues to influence clinical decision-making, potentially leading to delayed initiation in non-diabetic patients with heart failure. Conversely, greater baseline optimization of other GDMT components was positively associated with SGLT2i prescription. Each additional class of guideline-directed therapy was associated with a 31% higher likelihood of receiving an SGLT2 inhibitor, suggesting a “foundation-first” approach where clinicians introduce newer therapies after establishing core treatments.

Temporal trends indicated a progressive increase in SGLT2i utilization over the study period. This rise coincided with the publication of pivotal trials and the subsequent integration of SGLT2 inhibitors into international heart failure guidelines. The early years of the cohort, preceding the widespread endorsement of these drugs for heart failure, showed lower uptake, while later years reflected broader adoption. This temporal evolution underscores the impact of evolving evidence on clinical practice and highlights the lag between trial publication and routine implementation.

Exploratory time-to-event analyses suggested that patients treated with SGLT2 inhibitors experienced lower rates of heart failure hospitalization and all-cause mortality compared to those who did not receive the therapy. Kaplan–Meier curves showed higher event-free survival in the SGLT2i group, with statistically significant differences by log-rank testing. However, the authors emphasize that these findings are associative rather than causal. The observational design of the study is subject to residual confounding and treatment selection bias, as patients receiving SGLT2 inhibitors tended to have more favorable baseline clinical profiles and greater overall GDMT optimization.

The study acknowledges several limitations that impact the generalizability of its findings. The retrospective design precludes causal inference, and the population was derived exclusively from tertiary care centers, which may not represent primary or secondary care settings. Additionally, the subgroup of patients with improved ejection fraction was small, limiting the statistical power for specific analyses in this group. The temporal span of the study, covering periods of rapidly changing therapeutic paradigms, means that prescribing patterns in earlier years likely underestimate contemporary utilization levels.

These findings highlight actionable opportunities to improve the implementation of heart failure care in Saudi Arabia. Strategies that promote earlier integration of SGLT2 inhibitors alongside other GDMT components, address renal-related prescribing concerns, and reduce reliance on diabetes status as a trigger for initiation could help close the gap between evidence and practice. The study underscores the need for clinician education and system-level interventions to ensure that eligible patients receive foundational therapies regardless of comorbidity burden or renal function.

Future research should focus on prospective and implementation-focused studies that incorporate system-level variables, prescribing timelines, and healthcare policy factors. Understanding the specific barriers to adoption in regional practice will be essential for developing targeted interventions that enhance the consistency and quality of heart failure care. By identifying phenotype-specific patterns and key clinical determinants of prescribing, this study provides a valuable baseline for monitoring improvements in real-world adoption of guideline-directed therapies.

The heterogeneous utilization of SGLT2 inhibitors in this real-world cohort serves as a reminder that strong trial evidence does not automatically translate into uniform clinical practice. Addressing modifiable barriers, including clinician familiarity, therapeutic sequencing practices, and system-level factors, remains a priority for improving patient outcomes. As heart failure continues to be a major global health problem, ensuring equitable and evidence-based access to foundational therapies is crucial for reducing morbidity and mortality in affected populations.

Among patients prescribed SGLT2 inhibitors, 96.3% initiated the medication following a formal heart failure diagnosis, whereas only a minor share received treatment beforehand. Baseline comparisons between study groups also revealed clear demographic distinctions. Patients receiving SGLT2 inhibitors were significantly younger than non-recipients, with a median age of 64 years compared to 70 years, and a substantially higher proportion fell below 65 years of age. Recipients were also more frequently categorized into milder New York Heart Association functional classes at baseline. Notably, multivariable modeling demonstrated that while younger age remained an independent predictor of prescription, patient sex showed no independent association with SGLT2 inhibitor uptake after controlling for demographic and clinical factors.

The investigation also tracked how clinicians combined SGLT2 inhibitors with other foundational therapies across distinct ejection fraction definitions. Guideline definitions categorized patients into reduced ejection fraction at 40% or lower, mildly reduced between 41% and 49%, preserved at 50% or higher, and improved ejection fraction where an initial measurement of 40% or below subsequently rose above 40%, which accounted for just 12 patients. Evaluating baseline medical therapy showed that patients prescribed SGLT2 inhibitors were significantly more likely to receive each individual pillar of guideline-directed care, including beta-blockers, mineralocorticoid receptor antagonists, and renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors. Consequently, a substantially higher share of SGLT2 inhibitor recipients were managed with three or more guideline-directed medication classes compared to non-recipients.

The multicenter study, conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines, provides unique insight into regional care environments. In the Saudi governmental healthcare framework, cardiovascular medications are supplied without direct expense to patients. Because financial barriers and direct out-of-pocket drug costs are largely removed in this setting, the researchers observed that prescribing discrepancies are primarily shaped by clinician familiarity, therapy sequencing habits, and institutional practices. Broader regional evidence, such as findings from the PEACE MENA registry and Middle Eastern clinical reviews, indicates that guideline implementation often encounters challenges in patients carrying heavy comorbidity burdens, particularly when complex renal dosing and clinical monitoring requirements generate therapeutic hesitation.

The paper contextualized the rationale for broad uptake against established cardioprotective mechanisms, noting that SGLT2 inhibitors provide benefits through osmotic diuresis, enhanced myocardial energetics, favorable renal-cardiac interactions, and the attenuation of inflammation and oxidative stress. Standardized data collection captured diverse underlying disease etiologies, spanning ischemic cardiomyopathy and non-ischemic causes such as hypertensive, valvular, tachycardia-induced, inflammatory, and congenital conditions, alongside biomarkers including B-type natriuretic peptide. To evaluate longitudinal outcomes among the consecutive cohort, investigators applied Kaplan-Meier analyses and time-dependent multivariable Cox proportional hazards modeling using Stata software. In these exploratory evaluations, event-free survival differences emerged within the first year of follow-up and persisted over time, while the reduction in all-cause mortality reached statistical significance despite a low overall tally of deaths.

Subject of Research: Real-world utilization patterns and barriers to SGLT2 inhibitor prescription in heart failure patients in Saudi Arabia

Article Title: Utilization Patterns and Barriers to Sodium–Glucose Cotransporter-2 Inhibitor Prescription in Patients with Heart Failure: Real-World Evidence from Saudi Arabia

Article References: Alfehaid, L., Alkhezi, O., Alrayes, R., Alsuwaylihi, A., Alharbi, A., Aldosari, B., & Badreldin, H. (2026). Utilization Patterns and Barriers to Sodium–Glucose Cotransporter-2 Inhibitor Prescription in Patients with Heart Failure: Real-World Evidence from Saudi Arabia. Cardiology and Therapy, 15(3), 281-299. https://doi.org/10.1007/s40119-026-00458-4

Image Credits: AI Generated

DOI: 10.1007/s40119-026-00458-4

Keywords: Heart Failure, SGLT2 Inhibitors, Saudi Arabia, Clinical Practice, Renal Function, Guideline-Directed Therapy, Retrospective Cohort, Cardiology, Utilization, Patterns, Barriers, Sodium