Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, β-cell function and insulin resistance in type 2 diabetic patients

Diabetes Res Clin Pract. 2012 Oct;98(1):51-60. doi: 10.1016/j.diabres.2012.05.022. Epub 2012 Jun 9.

Abstract

Aims: To evaluate the impact on glycemic control, insulin resistance, and insulin secretion of sitagliptin+metformin compared to metformin in type 2 diabetic patients.

Methods: Patients were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to sitaglipin 100 mg or placebo for 12 months. We evaluated at 3, 6, 9, and 12 months: body mass index (BMI), glycemic control, fasting plasma insulin (FPI), HOMA-IR, HOMA-β, fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), C-peptide, glucagon, adiponectin (ADN), and high sensitivity-C reactive protein (Hs-CRP). Before, and after 12 months since the addition of sitagliptin, patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp, with subsequent arginine stimulation.

Results: Both treatments similarly decreased body weight, and BMI; on the other hand, they both improved glycemic control, glucagon and HOMA-IR, but sitagliptin+metformin were more effective in reducing these parameters. Sitagliptin+metformin, but not placebo+metformin, decreased FPPr, FPPR/FPI ratio, and increased C-peptide values, even if no differences between the groups were recorded. Sitaglitin+metformin gave also a greater increase of HOMA-β, M value, C-peptide response to arginine and disposition index compared to placebo+metformin group.

Conclusions: Other than improving glycemic control, sitagliptin+metformin also improved β-cell function better than metformin alone.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Blood Glucose / metabolism
  • C-Peptide / blood
  • C-Reactive Protein / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Exercise
  • Fasting / blood
  • Female
  • Glucagon / blood
  • Glucose Clamp Technique
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / pharmacology
  • Insulin Resistance*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism*
  • Italy
  • Male
  • Metformin / administration & dosage*
  • Metformin / pharmacology
  • Middle Aged
  • Pyrazines / administration & dosage*
  • Pyrazines / pharmacology
  • Sitagliptin Phosphate
  • Treatment Outcome
  • Triazoles / administration & dosage*
  • Triazoles / pharmacology

Substances

  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Pyrazines
  • Triazoles
  • hemoglobin A1c protein, human
  • C-Reactive Protein
  • Glucagon
  • Metformin
  • Sitagliptin Phosphate