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



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.



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.



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.
University of Pavia, Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, Pavia , Italy. giuseppe.derosa@unipv.it
Giuseppe
G
Derosa
Anna
A
Carbone
Angela
A
D'Angelo
Fabrizio
F
Querci
Elena
E
Fogari
Arrigo Fg
AF
Cicero
Pamela
P
Maffioli
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage*
D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate