OBJECTIVES: Metformin and sulfonylureas, used for Type 2 Diabetes Mellitus (T2DM) have been associated with electrolyte and acid-base imbalances. These imbalances can result in complications such as hyperkalemia and cardiac impairments which are particularly problematic for colorectal cancer patients (CRC). We aim to quantify the risk for electrolyte and acid-base imbalances associated with metformin vs sulfonylurea use in elderly CRC patients with T2DM, where the question remains unexamined.

METHODS: Using the SEER-Medicare data (2015-2019), we created a retrospective cohort of CRC patients, 65 years and older who initiated T2DM treatment using either metformin or sulfonylureas. We used descriptive statistics to assess differences in the treatment groups and time to event analysis namely Kaplan Meier survival curves, log-rank tests, and Cox proportional hazard models to quantify the association between the T2DM treatment choice and development of electrolyte and acid-base imbalances in this population.

RESULTS: Overall, 1724 patients who were mostly male 1155 (59%), and white 1512 (77%) were analyzed. Of these, 1484 initiated metformin while 238 used sulfonylureas. During follow-up (median = 638 days), 30 (2.02%) of the metformin users and 12 (5.04%) of the sulfonylurea users were newly diagnosed with an electrolyte or acid-balance imbalance yielding an unadjusted hazard ratio (HR) of 2.66 (95% CI: 1.36-5.19). After accounting for possible confounders such as age, sex, race, geographic region, cancer stage, Charlson comorbidity index, time since CRC diagnosis, we found that patients initiating T2DM treatment using Sulphonylureas had statistically higher risk for electrolyte and acid-base imbalances than metformin users (adjusted HR: 2.13; 95% CI: 1.06–4.30).

CONCLUSIONS: This study suggests that sulfonylureas may result in a higher risk of electrolyte imbalance in direct comparison with metformin in elderly CRC patients. More studies are needed to confirm this finding and to clarify its clinical implications.