Temporally Phenotyping GLP-1RA Case Reports with Large Language Models: A Textual Time Series Corpus and Risk Modeling

Accurate blood glucose forecasting using continuous glucose monitoring (CGM) data can support the early prediction of dysglycemic risk. However, current neural-network-based forecasting models treat CGM data as a purely numerical sequence without integrating the contextual information contained in CGM signal morphology. Recently, large language models (LLMs) have shown promise for time-series forecasting, yet their role as agentic context extractors in diabetes care remains largely unexplored. In this study, we bridge glucose forecasting and LLM-based contextualization by developing GlyRAG, a context-aware, retrieval-augmented forecasting framework that uses an LLM as a contextualization agent to summarize glucose morphology directly from a timed CGM window. The generated CGM-only narrative is embedded and fused with patch-based glucose representations, while a retrieval module incorporates similar historical training episodes through cross-attention. We evaluate GlyRAG on the OhioT1DM and AZT1D datasets for 5-, 30-, and 60-minute forecasting horizons. Compared with strong CGM-only baselines, GPT-4 GlyRAG significantly improves long-horizon root mean square error (RMSE) over PatchTST on both datasets. For example, RMSE decreases from 13.8 to 10.6 at 30 minutes and from 23.1 to 20.2 at 60 minutes on OhioT1DM. LLaMA 3.1 produces smaller but significant long-horizon gains, suggesting that the contextualization pipeline is not limited to GPT-4. Clinical error-grid analyses further show that approximately 85 percent of predictions fall within the clinically acceptable Clarke Error Grid Zones A and B. These results suggest that CGM-derived linguistic context and case-based retrieval can improve long-horizon glucose forecasting without requiring additional sensing modalities.

Clinical decisions are prospective, but clinical language models are often evaluated on retrospective records that reveal the final diagnosis, treatment response, and outcome. Such evaluations may reward the use of future information rather than reasoning under the uncertainty present at the decision point. We introduce a paired benchmark for measuring outcome-conditioned shifts consistent with hindsight bias in clinical temporal reasoning. It contains 171 case reports from the PubMed Central Open Access Subset---40 sepsis and 131 GLP-1/diabetes cases---represented as both textual narratives and human-annotated and LLM-generated textual time series (TTS). For each case, questions are tied to a clinically meaningful cutoff and paired with a prospective reference answer and an outcome-consistent hindsight trap. Models answer each question using either a TTS truncated at the cutoff or the complete timeline; additional conditions vary the narrative source (original or synthetic) and TTS annotation source (human or LLM). We evaluate accuracy (Acc), hindsight trap rate (HTR), answer instability rate (AIR), and hindsight bias rate (HBR), each of which captures different signals of hindsight bias. Across GPT 5.6 Sol, Gemma 4, GLM 5.2, and Opus 5, full timeline exposure produces consistent hindsight-sensitive shifts, while temporal masking reduces bias without lowering accuracy.

Large Language Models (LLMs) are increasingly being investigated for physiological time-series prediction, yet their effectiveness may depend not only on the model itself, but also on how physiological information is represented and presented at inference time. This study investigates prompt-based general-purpose LLMs for postprandial hyperglycemia and hypoglycemia prediction in individuals with type 1 diabetes. Using the OhioT1DM dataset, we evaluate multiple open-weight LLMs under zero-shot and few-shot inference across prediction horizons of 30, 60, and 90 minutes. The analysis varies both the textual representation of the available physiological information and the amount of information exposed to the model, ranging from glucose observations alone to derived descriptors and additional contextual variables related to insulin, meals, carbohydrates, and physical activity. Performance is compared with conventional patient-specific supervised models and with Gluco-LLM, a language-model-based architecture explicitly adapted to glucose time-series forecasting. Results show a marked task-dependent behavior. Conventional supervised models achieve the strongest performance for hyperglycemia prediction, whereas the best observed prompt-based LLM configurations improve performance for hypoglycemia across all investigated horizons. The effectiveness of prompt-based inference is also strongly influenced by how physiological information is represented, while providing additional contextual information does not lead to a systematic improvement. Overall, these findings highlight physiological information representation as a central design factor in prompt-based LLM approaches to glycemic-event prediction.