Effectiveness and Implementation of Digital Health Interventions on Physiological, Psychological, and Functional Outcomes in Adults With Multimorbidity: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Multimorbidity involves heterogeneous disease combinations, treatment burden, competing priorities, and complex care pathways. Digital health interventions (DHIs) may support monitoring, self-management, and care coordination, but their effects on health-related outcomes remain uncertain. Objective: This systematic review and meta-analysis evaluated the effectiveness of DHIs on physiological, psychological, and functional outcomes in adults with multimorbidity, summarized implementation outcomes, and explored intervention-multimorbidity matching patterns. Methods: PubMed, Web of Science Core Collection, Embase, Cochrane Library, CINAHL with Full Text, Scopus, gray literature sources, trial registries, reference lists, and forward citations were searched through April 7, 2026. English-language randomized or cluster-randomized trials enrolled adults with 2 or more chronic conditions and compared a DHI with a comparator lacking the same digital component. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses used restricted maximum likelihood estimation, Hartung-Knapp adjustment, and Nagashima-Noma-Furukawa prediction intervals. Certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. Results: In total, 36 reports (37 trials) were included. A total of 7 were rated as high risk of bias and 29 as having some concerns; none was rated as low risk overall. No statistically significant pooled effects were observed for glycated hemoglobin, blood pressure, mortality, hospitalization, or readmission, depression response, health-related quality of life, or pain-related functional impact or disability. For glycated hemoglobin, 6 studies (3992 participants) yielded a mean difference of -0.12 percentage points (95% CI -0.36 to 0.11; 95% prediction interval -0.70 to 0.43). For systolic blood pressure, 6 studies including 5596 participants yielded a mean difference of -3.40 mm Hg (95% CI -8.94 to 2.14; 95% prediction interval -19.15 to 13.03). Depression severity was the only outcome whose pooled 95% CI favored the intervention (8 studies; 1861 participants; standardized mean difference -0.49, 95% CI -0.82 to -0.16), but its prediction interval spanned benefit to harm (-1.53 to 0.51). Certainty was low or very low for all 7 GRADE-assessed outcomes. Implementation findings suggested feasibility, especially with monitoring, coaching, or clinician contact, but reporting was heterogeneous. Conclusions: Current evidence does not support consistent, transferable benefits of DHIs across most outcomes in adults with multimorbidity. Their real-world value may depend less on technology type than on alignment among intervention mechanisms, patient complexity, outcomes, and delivery context. Future DHIs should be adaptive, burden-sensitive, and workflow-integrated, linking digital data to patient priorities, clinician responses, and care coordination.