Common diabetes drugs may trigger prescribing cascades that add extra medications

People with type 2 diabetes are frequently prescribed additional medications to treat the side effects of drugs they were already taking, according to an analysis of two large routine healthcare databases from Scotland and Wales. The study, published in BMC Medicine, identified seven potential prescribing cascades — situations in which a new drug is given to treat an adverse reaction caused by another drug — among twelve medication pairs examined.

Researchers led by William Berthon and Peter Hanlon conducted two parallel cohort studies using prescription sequence symmetry analysis, a method that tests whether one medication is more often started after, rather than before, another. If a drug’s known side effect leads to a new prescription, the sequence should appear asymmetrically. The team drew data from the Scottish Diabetes Research Network national diabetes registry and the Welsh Secure Anonymised Information Linkage Databank between January 2015 and December 2023. Adults aged 40 or older with type 2 diabetes were eligible if they began both an index medication and a corresponding marker medication within a 365-day window. Twelve index-marker pairs were selected in advance from published literature, and adjusted sequence ratios were calculated after accounting for secular prescribing trends, with values above 1.0 indicating a potential cascade. Estimates from the two datasets were pooled using random-effects meta-analysis.

In total, 387,338 eligible individuals came from the Scottish registry and 296,582 from the Welsh databank. Seven of the twelve medication dyads showed evidence of a prescribing cascade. Sodium-glucose cotransporter-2 inhibitors, a widely used class of diabetes drugs, were followed by antibiotics for urinary tract infections (pooled adjusted sequence ratio 1.14, 95% confidence interval 1.10–1.17), antifungals (1.64, 1.58–1.69) and overactive bladder medications (1.16, 1.00–1.34). Thiazolidinediones were followed by loop diuretics (2.23, 1.28–3.89), and calcium channel blockers were followed by loop diuretics (1.80, 1.46–2.23). Statins were followed by overactive bladder medications (1.32, 1.02–1.73) and hypnotics (1.45, 1.29–1.62). Findings were directionally consistent across demographic and clinical subgroups, and sensitivity analyses examined age, sex, socioeconomic position, comorbidity and shorter observation windows of 90 and 180 days.

The mechanism behind each cascade reflects the known adverse drug reaction profile of the index medication. In each case, the sequence symmetry analysis cannot prove causation in an individual patient, but an adjusted ratio consistently above 1.0 across two independent national datasets suggests that the ordering of prescriptions is unlikely to be explained by chance or by underlying prescribing trends alone.

Recognising adverse drug reactions as a possible cause of new symptoms, they suggest, may identify opportunities to stop or modify the causative medication where appropriate, potentially reducing treatment burden. The study is a database analysis of routine prescribing records rather than a clinical trial, so it documents associations in the sequence of prescriptions rather than testing whether any intervention can safely reduce polypharmacy. The article was published as an open-access research paper on 22 October 2026, with the authors noting that the shared version is subject to further editorial edits before the final version of record.

Subject of Research: Prescribing cascades among people with type 2 diabetes analysed in two routine healthcare databases

Article Title: Prescribing cascades in people with type 2 diabetes: analyses of two representative routine healthcare databases

Article References: Berthon, W., Doherty, A. S., Wallace, E., Moriarty, F., McGurnaghan, S. J., Blackbourn, L. A. K., Walker, L. E., Colhoun, H. M., McAllister, D. A., & Hanlon, P. (2026). Prescribing cascades in people with type 2 diabetes: analyses of two representative routine healthcare databases. BMC Medicine. https://doi.org/10.1186/s12916-026-05333-6

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05333-6

Keywords: prescribing cascades, type 2 diabetes, polypharmacy, adverse drug reactions, prescription sequence symmetry analysis, SGLT2 inhibitors, statins, thiazolidinediones, calcium channel blockers, loop diuretics, Scottish Diabetes Research Network, SAIL Databank