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Introduction: Stress hyperglycaemia (SH), defined as transient hyperglycaemia during illness, is seen in up to 50% of inpatients and may progress to glucose intolerance in a significant proportion. SH is also associated with increased mortality. Despite this, there is no consensus on definition and management. Existing work focuses on single disease groups, frequently reporting adverse outcomes and variable success with therapies. There is, however, a scarcity of work profiling individuals with SH in detail. It is hoped that this approach may contribute to individualised management and improved outcomes for people with the condition. Methods: The central hypotheses of this work focus on metabolic profiling and were examined through a prospective observational study. Participants were allocated into study groups based on glucose levels. A 30-day follow-up was organised for people with SH. Novel biomarkers, tools and a diabetes risk calculator were employed to provide the most detailed profile currently available of individuals with stress hyperglycaemia. Finally, results from the first multicentre trial to bear on the effect of metformin in SH are presented. Results: The prevalence of SH was 34% and 31% in prospective (n=62) and metformin (n=52) studies respectively. People with SH had lower fasting insulin levels and insulin resistance. Otherwise, few differences were found. Metabolic profile, glycaemic variability, and HbA1c values were similar in both groups. Metabolic abnormalities and marked glycaemic excursions were also seen in both groups. Metformin was well tolerated but did not result in significantly reduced glucose variability or levels during the study period. Conclusions: People with SH do not appear to be phenotypically different from people without the condition. Marked hyper- and hypoglycaemia are common in hospital patients despite apparent normal glucose levels. Increased vigilance as well as timely and appropriate interventions could significantly improve outcomes for these individuals. Open Access