A randomized, double-blind, placebo-controlled trial evaluating sitagliptin action on insulin resistance parameters and β-cell function

Expert Opin Pharmacother. 2012 Dec;13(17):2433-42. doi: 10.1517/14656566.2012.730519. Epub 2012 Oct 15.

Abstract

Aim: To evaluate the impact on glycemic control, insulin secretion and on insulin resistance of a sitagliptin + metformin combination compared to metformin monotherapy in type 2 diabetic, naïve to treatment, patients.

Materials and methods: A total of 178 Caucasian type 2 diabetic patients were randomized to take sitagliptin 100 mg once a day or placebo in addition to previously taken metformin, for 12 months. The authors 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, retinol binding protein-4 (RBP-4), visfatin, and chemerin. Before and 12 months after the addition of sitagliptin, patients underwent tests to assess insulin sensitivity and insulin secretion.

Results: Sitagliptin + metformin gave a better decrease of glycemic control, HOMA-IR and glucagon levels compared to placebo + metformin; sitagliptin + metformin also better increased HOMA-β and all β-cell measurements recorded after the clamp. Regarding adipocytokines, sitagliptin + metformin better reduced RBP-4, visfatin and chemerin levels, compared to placebo + metformin.

Conclusion: When metformin alone is not enough to reach an adequate glycemic control, sitagliptin can be a valid option, because of its effects in reducing insulin resistance and in preserving β-cell function.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Resistance
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Pyrazines / administration & dosage*
  • Sitagliptin Phosphate
  • Triazoles / administration & dosage*

Substances

  • Hypoglycemic Agents
  • Pyrazines
  • Triazoles
  • Metformin
  • Sitagliptin Phosphate