Sarcopenia is associated with a greater risk of polypharmacy and number of medications: a systematic review and meta‐analysis

**Background:** Polypharmacy, commonly defined as the concurrent use of five or more medications, affects more than one third of older people worldwide and is associated with adverse drug reactions, disability, and hospitalizations. Sarcopenia—the pathological loss of muscle mass, strength, and function in older age—is associated with impaired physical function, hospitalization, and mortality. While a previous scoping review suggested an association between sarcopenia and polypharmacy in community-dwelling older adults, no quantitative synthesis had been performed. This meta-analysis aimed to investigate whether sarcopenia amplifies the risk of polypharmacy and is associated with a higher number of medications.

**Methods:** This systematic review and meta-analysis followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD: 42022337539). Two independent reviewers searched PubMed, Scopus, Web of Science, and Cochrane Library from inception until June 2022. Inclusion criteria were: observational studies (cross-sectional, longitudinal, case-control); adults aged ≥60 years; clear diagnostic criteria for sarcopenia (EWGSOP 1, EWGSOP 2, AWGS, FNIH, or CHS); clear criteria for polypharmacy (≥5 medications in 15 studies, ≥6 in one, ≥4 in one); and studies including both adults with and without sarcopenia. Data extraction and quality assessment using the MINORS tool were performed independently by two reviewers. Random-effects meta-analysis was used to calculate odds ratios (OR) for polypharmacy prevalence and mean differences (MD) for number of medications. Heterogeneity was assessed using I² statistics, and meta-regression explored sources of variability.

**Key Results:** Twenty-nine studies were included (17 assessing polypharmacy prevalence, 13 assessing number of medications, one study included in both analyses). The main analysis for polypharmacy (k=17, 2153 sarcopenic subjects, 8861 non-sarcopenic subjects) showed that sarcopenia was associated with a significantly higher prevalence of polypharmacy (OR: 1.65, 95% CI [1.23, 2.20], I²=84%, P<0.01). Subgroup analyses revealed significant associations in community-dwelling subjects (OR: 2.00, 95% CI [1.35, 2.97]) and outpatients (OR: 2.51, 95% CI [1.55, 4.07]), but not in inpatients (OR: 1.11, 95% CI [0.65, 1.89]) or nursing home residents. The association was significant in Europe (OR: 2.23, 95% CI [1.52, 3.27]) but not in Asia (OR: 1.42, 95% CI [0.97, 2.07]). Using EWGSOP criteria yielded a significant association (OR: 1.95, 95% CI [1.38, 2.76]), while AWGS criteria did not (OR: 1.30, 95% CI [0.81, 2.08]). For number of medications (k=13, 1312 sarcopenic subjects, 3470 non-sarcopenic subjects), sarcopenia was associated with significantly more medications (MD: 1.39, 95% CI [0.59, 2.19], I²=95%, P<0.01). This was significant in community-dwelling (MD: 0.66, 95% CI [0.11, 1.21]) and nursing home residents (MD: 0.90, 95% CI [0.51, 1.30]), but not in inpatients or outpatients. Sensitivity analyses excluding studies with comorbidities, malnutrition, or high risk of bias did not change the main findings. Meta-regression identified study population (community-dwelling, nursing home, inpatient, outpatient) as a significant source of variance for both outcomes (polypharmacy: r=−0.338, SE=0.1669, P=0.04; number of medications: r=0.589, SE=0.2615, P=0.02).

**Clinical Implications:** This meta-analysis provides quantitative evidence that sarcopenia is associated with a 65% higher odds of polypharmacy and approximately 1.4 additional medications. The association is strongest in community-dwelling older adults and outpatients, suggesting that healthcare settings with higher baseline medication use may mask the sarcopenia-polypharmacy relationship. The finding that the association was significant with EWGSOP but not AWGS criteria may reflect differences in diagnostic thresholds or underlying population characteristics. These results highlight the importance of medication review and deprescribing in older adults with sarcopenia, particularly given that certain drug classes (corticosteroids, antidiabetics, beta-blockers) may directly impair muscle function. Future research should clarify whether polypharmacy causally accelerates sarcopenia progression and whether judicious deprescribing can slow it.