Frailty Matters—Why Isn't It Guiding Clinical Decisions?

Abstract

Frailty is a powerful predictor of adverse outcomes in older adults, including disability, institutionalization, and mortality [1]. This geriatric syndrome denotes a decline in physiological reserve and reduced homeostatic capacity, increasing vulnerability to stressors such as acute illness, surgery, and hospitalization [2]. Prevalence estimates vary widely (3.5%–27.3%) depending on population characteristics and frailty definitions [3]. In the United States, approximately 15% of community-dwelling older adults are classified as frail [1]. In lower- and middle-income countries, where aging is mainly affected by socioeconomic disparities, limited healthcare access, and a higher burden of chronic diseases, frailty often manifests at younger ages [2]. Despite its well-established predictive value, frailty is not a decision node included in most medical guidelines [4].

Clinical decisions continue to prioritize disease-specific parameters and chronological age over physiological vulnerability measures like frailty [5]. This approach fails to account for the heterogeneity that defines aging. Standard treatment guidelines, often developed based on younger or healthier populations, do not address the complex interplay of chronic diseases and geriatric syndromes [2]. Most older adults live with multiple coexisting conditions—chronic diseases (e.g., diabetes, hypertension, arthritis) alongside geriatric syndromes (e.g., frailty, cognitive impairment, falls)—that interact to shape symptoms, treatment risks, and outcomes [5]. Frailty, for example, has been linked to increased healthcare utilization, poorer recovery, and higher mortality in older adults with chronic diseases. As populations age, frailty is gaining attention as a tool to improve risk stratification and guide individualized treatment decisions [2, 5].

Diabetes illustrates how frailty complicates treatment decisions in older adults [6]. One in four adults aged 65 and older has diabetes, often with cardiovascular disease, nephropathy, or neuropathy, all of which are associated with frailty. About half of older adults with diabetes meet the criteria for frailty, reflecting their greater physiological vulnerability [7]. Moreover, frail individuals with diabetes have higher risks of hypoglycemia, poor treatment tolerance, and functional decline. They may also not benefit from treatments that take years to show results [6]. Rigid glycemic targets may expose frail patients to harm, while complex medication regimens increase the risk of polypharmacy and adverse events. Instead of focusing on strict blood glucose levels, clinicians should tailor diabetes care to minimize harm and preserve independence [6]. Although frailty assessment may help guide treatment intensity and drug selection based on patient needs, it remains cast aside for treatment decisions for older adults with diabetes [8].

In this issue of the Journal of the American Geriatrics Society, Nguyen et al. [9] present an updated analysis of pooled data from the CANVAS and CREDENCE trials, examining the efficacy and safety of canagliflozin in 14,543 participants with type 2 diabetes, stratified by frailty status. Frailty, defined by a Frailty Index threshold of > 0.25, was present in 56% of participants. Despite their higher baseline risks, frail individuals experienced similar cardiovascular and survival benefits compared to non-frail participants (Figure 1). A reduction in the risk of major adverse cardiovascular events (MACE) was observed in frail (hazard ratio [HR]: 0.80, 95% confidence interval [CI]: 0.70–0.90) and non-frail (HR: 0.91, 95% CI: 0.75–1.09) participants, with no significant interaction by frailty status (p value = 0.27). Similar trends were shown for cardiovascular mortality and all-cause mortality. Adverse events were comparable between groups, though osmotic diuresis was more common in non-frail participants (p value for interaction = 0.01) [9].

These findings indicate that canagliflozin is an effective and safe therapeutic option for older adults with type 2 diabetes, regardless of frailty status. Unlike traditional glucose-lowering therapies that may increase the risk of hypoglycemia and treatment burden, sodium-glucose cotransporter-2 (SGLT2) inhibitors work through insulin-independent mechanisms by promoting urinary glucose excretion, leading to better metabolic control with minimal hypoglycemia risk [10]. Large trials have demonstrated the cardiovascular and renal benefits of SGLT2 inhibitors, including canagliflozin [10, 11]. SGLT2 inhibition induces mild diuresis and natriuresis, which also help manage hypertension and fluid overload—common concerns in older adults. Nguyen et al. [9] build upon this evidence by showing that these benefits are independent of frailty status, similar to what has been reported with dapagliflozin in the DELIVER trial [11]. Although these results are promising, they should be interpreted with caution when translating them into clinical practice [12]. Frail participants were more likely to have a longer duration of diabetes, higher HbA1c levels, and more cardiovascular risk factors, which might have influenced treatment effects not captured in the current analyses [9]. Additionally, SGLT2 inhibitors exert pleiotropic effects beyond glucose control, such as weight loss, which may be detrimental in frail older adults [12]. The benefits of canagliflozin must also be balanced against an increased risk of volume depletion, hypotension, and urinary tract infections, which are more prevalent in adults aged 75 and older [10].

The relevance of frailty for older adults has been discussed in clinical scenarios beyond diabetes care [13]. In cardiology, researchers have explored how frailty assessments can refine anticoagulation strategies for atrial fibrillation, aiming to optimize stroke prevention while minimizing bleeding risks [14]. In oncology, frailty measures have been tested to predict chemotherapy toxicity and to tailor treatment intensity. Frailty has also been linked to higher mortality and hospitalization rates among older adults with advanced chronic kidney disease [13]. Emerging evidence suggests it could help guide dialysis decisions. Surgical disciplines have begun incorporating frailty screening into preoperative evaluations, with early findings suggesting a possible role in optimizing postoperative outcomes [15].

Despite increasing recognition of frailty's importance in clinical research and practice, there is no clear framework for how it should influence treatment decisions [3]. Consider a 76-year-old woman with diabetes. Should clinicians adopt more relaxed glycemic targets to minimize her risk of hypoglycemia based on frailty alone? If she develops advanced chronic kidney disease, should frailty guide the decision on whether dialysis would provide meaningful benefits or impose undue burden? What about an 80-year-old man with atrial fibrillation—should he continue full-dose anticoagulation despite frailty increasing his fall risk, or should treatment be adjusted knowing his elevated stroke risk? These scenarios illustrate the need for a clear, evidence-based framework that will guide integrating frailty into clinical decision-making. Without clear evidence and structured frameworks, frailty may be recorded as another data point rather than a meaningful parameter to guide clinical decisions [13].

A promising way to make frailty more actionable in clinical practice is to include it in randomized controlled trials, as shown in Table 1. While some trials have incorporated frailty assessments, most are limited by small sample sizes, a predominance of White participants from high-income countries, and relatively young mean ages that do not fully represent geriatric populations [16-19]. The high variability in frailty measurement tools and their current use in only very specific research contexts further limit their practical interpretation. Moreover, frailty has not consistently modified treatment effects in recent trials. For example, in the HYVET trial, antihypertensive benefits remained consistent across all levels of frailty [4].

Integrating frailty into clinical decision-making tools deals with multiple methodological, structural, and practical barriers [3]. As with Nguyen et al. most evidence on frailty comes from observational studies or post hoc analyses of clinical trials [8, 9]. These study designs may introduce bias due to retrospective frailty assessment, often influenced by data availability and residual confounding related to differences in measured and, particularly, unmeasured baseline characteristics. Another major challenge is the lack of standardization in frailty assessment tools, with multiple instruments—such as the Physical Frailty Phenotype, Frailty Index, Clinical Frailty Scale, and FRAIL scale—varying in sensitivity, criteria, and applicability across clinical settings [3]. This inconsistency hinders a uniform approach to patient care, leading to unwarranted variability in treatment decisions. Unlike routinely measured biomarkers such as blood pressure or cholesterol, frailty lacks a single, universally accepted screening protocol. Time constraints in high-volume clinical settings further hinder implementation, as many frailty assessments require additional steps that may not fit within standard consultations [2, 3]. Moreover, reimbursement models do not incentivize frailty screening. Even when frailty is identified, treatment pathways rarely provide structured guidance on how to modify patient are accordingly, leaving clinicians uncertain about its practical implications. Non-pharmacological interventions such as resistance training and nutritional support hold the potential for mitigating frailty [20]. However, heterogeneity in study methodologies and frailty definitions complicates risk–benefit assessment and limits clinical applicability. Implementation remains difficult due to resource constraints, adherence challenges, and the need for multidisciplinary coordination [3].

A structured approach is necessary to transition frailty from a prognostic marker to a meaningful tool in clinical decision-making. Standardized frailty assessments across specialties should be embedded into electronic health records to facilitate routine use without overburdening clinicians [20]. Integrating frailty screening with comprehensive geriatric assessment (CGA) improves prognostic accuracy by incorporating functional status, cognition, comorbidities, and patient preferences [3]. Frailty alone should not determine treatment decisions or justify withholding care. Instead, it must be evaluated within CGA to guide personalized, evidence-based interventions that optimize outcomes while respecting individual goals [5]. Expanding randomized controlled trials to assess frailty as both a prognostic factor and an intervention target will strengthen its clinical utility. At the same time, policy reforms should provide financial support for frailty screening and incentivize its adoption in routine practice [13, 20].

Frailty is too important to ignore. It is one of the strongest predictors of poor health outcomes, but its role in clinical decision-making remains uncertain. The time has come to test whether frailty can inform treatment decisions for older adults. As populations age, guidelines must evolve beyond simple age cutoffs to address the complexities of aging. Standardizing assessments, incorporating frailty into clinical workflows, and strengthening evidence from clinical trials will determine its utility as a decision-making tool. A shift from age- and disease-based to frailty-informed and comprehensive care presents an opportunity for improvement. Still, its implementation must be guided by evidence, not assumption.

Márlon Juliano Romero Aliberti, Daniel F. Arteaga-Vargas, and Thiago Junqueira Avelino-Silva: reviewed, and prepared this editorial.

The founders had no role in the preparation or decision to publish this editorial.

The authors declare no conflicts of interest.

This publication is linked to a related article by Nguyen et al. To view this article, visit https://doi.org/10.1111/jgs.19444.