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Background: Unexpected weight loss (UWL) in patients consulting in primary care presents dilemmas for management because of the broad differential diagnoses associated with UWL. Research on the risks of serious disease among patients with UWL to date has largely taken place in secondary care, limiting generalizability to primary care patients. In this study, we use a large matched cohort study to estimate the risks of 12 serious diseases among patients presenting to primary care with UWL where this was recorded, stratified by age and sex, in order to inform a rational clinical approach to patients presenting with UWL. Methods: This was a retrospective matched cohort study using electronic health records (EHRs) from the UK Clinical Practice Research Datalink (CPRD). Each patient with UWL (ascertained from EHR coding) was matched to five patients without UWL and followed until the earliest of a diagnosis of the serious disease, date of death, exit from the CPRD database, or end of the study. Observed absolute risks of the 12 serious diseases were estimated as probabilities, and hazard ratios (HRs) were estimated with Cox proportional hazards models. Results: Between 2000 and 2012, 70 193 patients in CPRD had at least one record of UWL and were matched with 295 579 patients without UWL. Patients with UWL had significantly higher risk of nearly all serious diseases examined compared with patients without. HRs ranged from 1.43 for congestive heart failure [95% confidence interval (CI): 1.27–1.62] to 9.70 for malabsorption (95% CI: 6.81–13.82). The absolute risks of any given serious disease were relatively low (<6% after 1 year). The magnitude and rank order of absolute risks varied by age and sex. Depression was the most common diagnosis among women aged <80 with UWL (3.74% of women aged <60 and 2.46% of women aged 60–79), whereas diabetes was the most common in men <60 with UWL (2.96%) and cancer was the most common in men aged 60 and over with UWL (3.79% of men aged 60–70 and 5.28% of men aged ≥80). Conclusions: This analysis provides new evidence to patients and clinicians about the risks of serious disease among patients presenting with UWL in primary care. Depending on age and sex, the results suggest that workup for UWL should include screening for diabetes, thyroid dysfunction, depression, and dementia. If performed in a timely manner, this workup could be used to triage patients eligible for cancer pathway referral.

Original publication




Journal article


Journal of Cachexia, Sarcopenia and Muscle

Publication Date





2661 - 2668