Hemoglobin glycation index as a useful predictor of therapeutic responses to dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes

PLoS One. 2017 Feb 9;12(2):e0171753. doi: 10.1371/journal.pone.0171753. eCollection 2017.


Introduction: A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors.

Methods: This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI<0, n = 199) and high HGI (HGI≧0, n = 269).

Results: There were no significant group differences in mean changes of FPG after 1 year (-12.8 and -13.4 mg/dL in the low and high HGI groups, respectively). However, the patients with a high HGI had a significantly greater reduction in HbA1c from baseline compared to those with a low HGI (-1.9 versus -0.3% [-20.8 versus -3.3 mmol/mol]). Improvements in glycemic control were statistically significantly associated with the tested DPP-4 inhibitors in the high HGI group (-2.4, -1.4, -1.2 and -2.2% [-26.2, -15.3, -13.1 and -24.0 mmol/mol] for vildagliptin, linagliptin, saxagliptin and sitagliptin, respectively) but not in the low HGI group.

Conclusions: The HGI index derived from FPG and HbA1c may be able to identify who will have a better response to DPP-4 inhibitors.

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / therapeutic use
  • Adult
  • Aged
  • Biomarkers, Pharmacological / blood*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptides / therapeutic use
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Glycated Hemoglobin A / analysis
  • Glycated Hemoglobin A / metabolism*
  • Health Status Indicators
  • Humans
  • Linagliptin / therapeutic use
  • Male
  • Middle Aged
  • Nitriles / therapeutic use
  • Predictive Value of Tests
  • Prognosis
  • Pyrrolidines / therapeutic use
  • Retrospective Studies
  • Sitagliptin Phosphate / therapeutic use
  • Treatment Outcome
  • Vildagliptin


  • Biomarkers, Pharmacological
  • Blood Glucose
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Nitriles
  • Pyrrolidines
  • Linagliptin
  • saxagliptin
  • Vildagliptin
  • Adamantane
  • Sitagliptin Phosphate

Grant support

The authors received no specific funding for this work.