AIMS: To investigate the effect of serotonin transporter (5-HTT) polymorphisms on change in HbA1c levels six months after metformin initiation in type 2 diabetes patients.

MATERIALS AND METHODS: Participants of PROVALID (PROspective cohort study in patients with type 2 diabetes mellitus for VALidation of biomarkers) within the GIANTT (Groningen Initiative to ANalyse Type 2 Diabetes Treatment) cohort who initiated metformin were genotyped for combined 5-HTTLPR/rs25531 (L ∗L ∗, L ∗S ∗, and S ∗S ∗) and 5-HTT VNTR (STin 2.12, 12/-, and 10/-) polymorphisms, respectively. Multiple linear regression was applied to determine the change in HbA1c level from baseline date to six months across 5-HTTLPR/VNTR genotype groups, adjusted for baseline HbA1c, age, gender, triglyceride level, low-density lipoprotein level, and serum creatinine.

RESULTS: 157 participants were included, of which 56.2% were male. The average age was 59.3 ± 9.23 years, and the mean baseline HbA1c was 7.49% ± 1.21%. 5-HTTLPR was characterized in 46 patients as L ∗L ∗, 70 patients as L ∗S ∗, and 41 patients as S ∗S ∗ genotypes. No significant association was found between 5-HTTLPR and 5-HTT VNTR genotypes and change in HbA1c after adjustments.

CONCLUSIONS: 5-HTT polymorphisms did not affect HbA1c levels six months after the start of metformin. Further long-term studies in large samples would be relevant to determine which polymorphisms can explain the variation in response to metformin treatment.

Original languageEnglish
Article number7922486
Number of pages7
JournalJournal of Diabetes Research
Publication statusPublished - 22-Jan-2024


  • Humans
  • Male
  • Middle Aged
  • Aged
  • Female
  • Diabetes Mellitus, Type 2/drug therapy
  • Metformin/therapeutic use
  • Glycated Hemoglobin
  • Prospective Studies
  • Polymorphism, Genetic
  • Serotonin Plasma Membrane Transport Proteins/genetics
  • Genotype


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