Background: Large language models (LLMs) demonstrated advanced performance in processing clinical information. However,commercially available LLMs lack specialized medical knowledge and remain susceptible to generating inaccurate information.Given the need for self-management in diabetes, patients commonly seek information online. We introduce the Retrieval-augmentedInformation System for Enhancement (RISE) framework and evaluate its performance in enhancing LLMs to provide accurateresponses to diabetes-related inquiries.Objective: This study aimed to evaluate the potential of the RISE framework, an information retrieval and augmentation tool,to improve the LLM's performance to accurately and safely respond to diabetes-related inquiries.Methods: The RISE, an innovative retrieval augmentation framework, comprises 4 steps: rewriting query, information retrieval,summarization, and execution. Using a set of 43 common diabetes-related questions, we evaluated 3 base LLMs (GPT-4, AnthropicClaude 2, Google Bard) and their RISE-enhanced versions respectively. Assessments were conducted by clinicians for accuracyand comprehensiveness and by patients for understandability.Results: The integration of RISE significantly improved the accuracy and comprehensiveness of responses from all 3 baseLLMs. On average, the percentage of accurate responses increased by 12% (15/129) with RISE. Specifically, the rates of accurateresponses increased by 7% (3/43) for GPT-4, 19% (8/43) for Claude 2, and 9% (4/43) for Google Bard. The framework alsoenhanced response comprehensiveness, with mean scores improving by 0.44 (SD 0.10). Understandability was also enhanced by0.19 (SD 0.13) on average. Data collection was conducted from September 30, 2023 to February 5, 2024.Conclusions: The RISE significantly improves LLMs'performance in responding to diabetes-related inquiries, enhancingaccuracy, comprehensiveness, and understandability. These improvements have crucial implications for RISE's future role inpatient education and chronic illness self-management, which contributes to relieving medical resource pressures and raisingpublic awareness of medical knowledge.