Hypoglycemia after antimicrobial drug prescription for older patients using sulfonylureas
Open accessAbstract
IMPORTANCE: Certain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia. OBJECTIVE: To determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population. METHODS: We assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment. MAIN OUTCOMES AND MEASURES: Any hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure. RESULTS: In multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas. CONCLUSIONS AND RELEVANCE: Prescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.
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Sulfonylureas interact with a number of commonly used antimicrobials (fluoroquinolones, clarithromycin, sulfamethoxazole-trimethoprim, metronidazole, and fluconazole) that can dramatically increase their effective dose, leading to hypoglycemia.
“Notably, sulfonylureas interact with a number of commonly used antimicrobials (fluoroquinolones, clarithromycin, sulfamethoxazole-trimethoprim, metronidazole, and fluconazole) that can dramatically increase their effective dose, leading to hypoglycemia (159-161).”
From 6. Glycemic Goals, Hypoglycemia, and Hyperglycemic Crises: Standards of Care in Diabetes-2026. (2026) · cites this paper as [159]
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Experimental — accuracy not yet measuredMany antimicrobials interact with sulfonylureas to increase the effective sulfonylurea dose, which may precipitate hypoglycemia.
“Many antimicrobials (most commonly fluroquinolones and sulfamethoxazole-trimethoprim) interact with sulfonylureas to increase the effective sulfonylurea dose, which may precipitate hypoglycemia (118-120).”
From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [118]
The Results report higher rates of hypoglycemia after several antimicrobials, including levofloxacin, ciprofloxacin, and sulfamethoxazole-trimethoprim, in patients taking sulfonylureas. The Methods describe some antimicrobials as potentially potentiating sulfonylureas, but the cited passages do not establish that these drugs increase the effective sulfonylurea dose; that specific mechanism is unsupported. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMany antimicrobials, most commonly fluoroquinolones and sulfamethoxazole-trimethoprim, interact with sulfonylureas to increase the effective sulfonylurea dose, which may precipitate hypoglycemia.
“Many antimicrobials (most commonly fluroquinolones and sulfamethoxazole-trimethoprim) interact with sulfonylureas to increase the effective sulfonylurea dose, which may precipitate hypoglycemia”
From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [127]
The Results report higher hypoglycemia rates after levofloxacin, ciprofloxacin, and sulfamethoxazole-trimethoprim prescriptions in older sulfonylurea users. The Methods describe possible potentiation of sulfonylureas, but our copy does not establish that these drugs increase the effective sulfonylurea dose or that fluoroquinolones and sulfamethoxazole-trimethoprim are the most common interacting antimicrobials. The Results also found no significant association for moxifloxacin, another fluoroquinolone. (LLM, conf=0.85)
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References 43 · Cited by 75
- Authors
- Parekh, T. M., Raji, M., Lin, Y.-L., Tan, A., Kuo, Y.-F., & Goodwin, J. S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Corresponding author
- Goodwin, James S.
- Venue
- JAMA Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2014-10-01
- Volume
- 174
- Issue
- 10
- Pages
- 1605
- ISSN
- 2168-6106 (ISSN-L)
- PMC
- PMC4878670
- OpenAlex
- W2110349466
- Cited by
- 75
- References
- 43
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 2 · 2016: 6 · 2015: 7 · 2012: 1
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- JAMA Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000071)
- Agency for Healthcare Research and Quality (1R24HS022134-0, R24HS022134)
- National Institute on Aging (R01AG033134, P30AG024832)
- National Cancer Institute (K05CA134923)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- hypoglycemia, sulfonylureas, glipizide, glibenclamide, older adults, clarithromycin, levofloxacin, trimethoprim-sulfamethoxazole, metronidazole, ciprofloxacin, Medicare spending, hospitalization, emergency department visits, number needed to harm, adverse drug reactions
- MeSH terms
- Aged, Aged, 80 and over, Anti-Infective Agents, Ciprofloxacin, Drug Interactions, Female, Glyburide, Glipizide, Medicare, Humans, Hypoglycemia, Hypoglycemic Agents, Male, Metronidazole, Morbidity, Drug Prescriptions, Retrospective Studies, Risk Factors, Sulfonylurea Compounds, Texas, United States, Trimethoprim, Sulfamethoxazole Drug Combination, Logistic Models, Odds Ratio, Health Care Costs, Clarithromycin, Levofloxacin
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