Characterization of Patients With Type 2 Diabetes Experiencing Severe Hypoglycemia Exclusively due to Dipeptidyl Peptidase-4 Inhibitor Monotherapy

Geriatr Gerontol Int. 2025 Dec;25(12):1940-1947. doi: 10.1111/ggi.70240. Epub 2025 Nov 3.

Abstract

Aim: Hypoglycemia during dipeptidyl peptidase-4 inhibitor (DPP4i) monotherapy is rare; however, we encountered four such cases, prompting further analysis. Therefore, this study analyzed the characteristics of patients who experienced similar levels of hypoglycemia during monotherapy with other oral hypoglycemic agents or insulin.

Methods: We screened 553 201 patients who visited the Critical Care and Emergency Center of our hospital from January 1, 2008, to December 31, 2019, and identified 148 patients with severe hypoglycemia taking an oral hypoglycemic agent or insulin. The patients were divided into three groups: Group D (N = 4, DPP4i alone), Group I (N = 104, insulin alone), and Group S (N = 40, sulfonylurea alone).

Results: The patients in Group D (85.5 years) were significantly older than those in Group I (75.0 years) (p = 0.043), and those in Group S (81.5 years) were also significantly older than those in Group I (p < 0.0001). During blood sampling performed at the Critical Care and Emergency Center, the median glucose level was highest in Group D (53 mg/dL), followed by Groups I (33 mg/dL, p = 0.0137) and S (31 mg/dL, p = 0.0120). In the same samples, glycosylated hemoglobin A1c levels were lower in Group D (5.6%) than in Group I (7.3%, p = 0.012). The estimated glomerular filtration rate did not differ significantly between groups.

Conclusions: DPP4is are generally low-risk hypoglycemic agents, with a high risk of hypoglycemia, particularly observed in older adults. These findings underscore the importance of vigilant monitoring and personalized treatment strategies to mitigate hypoglycemia risks in this population, thereby informing clinical practice and guiding future research.

Keywords: dipeptidyl peptidase‐4 inhibitor; hypoglycemia; monotherapy; type 2 diabetes mellitus.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / administration & dosage
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemia* / chemically induced
  • Hypoglycemic Agents* / administration & dosage
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Insulin / administration & dosage
  • Insulin / adverse effects
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sulfonylurea Compounds / adverse effects

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Blood Glucose
  • Insulin
  • Sulfonylurea Compounds
  • Glycated Hemoglobin