# Concomitant use of antidepressants and oral antidiabetic drugs and the risk of hypoglycemia

> **NIH NIH R36** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $69,054

## Abstract

PROJECT SUMMARY
The prevalence of depression and pharmacologic treatments for depression are both approximately twice the
prevalence of these in non-diabetic populations. However, case reports, animal studies, and epidemiologic
studies have suggested an increased risk of hypoglycemia associated with antidepressant use. One potential
mechanism explaining this association is possible drug-drug interactions (DDIs) between antidepressants and
oral antidiabetic drugs (OADs). Certain selective serotonin reuptake inhibitors (SSRIs) inhibit the CYP2C9
enzyme, which is responsible for the metabolism of some diabetes medications. Only one epidemiologic study
investigating this potential DDI has been published and reported imprecise results. There is a need for
evidence generated by well-designed studies, particularly in U.S. populations to better understand the clinical
implications of this potential DDI. The goal of the proposed research is to examine the potential effect of co-
utilization of CYP2C9-metabolized OADs and CYP2C9-inhibiting antidepressants on the risk of serious
hypoglycemia, using rigorous study design approaches and a database of Medicare claims linked with
electronic health records (EHRs) for a population of patients 65 years or older who have interacted with the
UNC healthcare system. In Aim 1, we will determine the prevalence of concomitant use of OADs and
antidepressants that are either metabolized by or inhibit the CYP2C9 enzyme and evaluate prescribing trends
over time and estimate the association between concomitant OAD and antidepressant use and hypoglycemia
using an active comparator design. Among a population of OAD users, we will compare the risk of
hypoglycemia between those who concomitantly receive CYP2C9 inhibiting antidepressants and those who
receive antidepressants that are not thought to interact with CYP2C9. In Aim 2, we will validate an algorithm for
identifying the outcome severe hypoglycemia using ICD-10-CM codes mapped from an existing ICD-9-CM
based algorithm. Leveraging appropriate and reliable study-design approaches in combination with rich
healthcare data can provide evidence on the potential link between OAD-antidepressant interactions and
severe hypoglycemia. This question is especially important, given the need to balance adequate treatment of
mental health with the immense burden of hypoglycemia. The results from this study will inform clinical care for
diabetes patients and assist healthcare providers in optimizing treatment for prevalent comorbid mental health
conditions. In the long-term, this work will be a part of the much-needed effort to generate reliable evidence for
patients and providers managing chronic conditions with complex pharmacologic treatment strategies.

## Key facts

- **NIH application ID:** 10526807
- **Project number:** 1R36AG075394-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Sara Z. Dejene
- **Activity code:** R36 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,054
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10526807

## Citation

> US National Institutes of Health, RePORTER application 10526807, Concomitant use of antidepressants and oral antidiabetic drugs and the risk of hypoglycemia (1R36AG075394-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10526807. Licensed CC0.

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