Clinical features, risk factors, diagnosis, and treatment of trimethoprim-sulfamethoxazole-induced hypoglycemia

Front Endocrinol (Lausanne). 2023 Feb 8:14:1059522. doi: 10.3389/fendo.2023.1059522. eCollection 2023.

Abstract

Objective: Hypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.

Methods: Case reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.

Results: A total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.

Conclusion: Hypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.

Keywords: hypoglycemia; neuroglycopenic symptoms; pneumocystis pneumonia; seizure; trimethoprim-sulfamethoxazole.

Publication types

  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Child, Preschool
  • Female
  • Glucose / adverse effects
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemia* / diagnosis
  • Hypoglycemia* / drug therapy
  • Infant
  • Male
  • Middle Aged
  • Renal Insufficiency*
  • Risk Factors
  • Trimethoprim, Sulfamethoxazole Drug Combination / adverse effects
  • Young Adult

Substances

  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Glucose

Grants and funding

This research was supported by the Inclusive Policy and Innovative Environment Construction Program of Hunan Province(Grant numbers: 2021SK53707).