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.
OBJECTIVE
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.
Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@unipv.it
Giuseppe
G
Derosa
Anna
A
Carbone
Ivano
I
Franzetti
Fabrizio
F
Querci
Elena
E
Fogari
Lucio
L
Bianchi
Aldo
A
Bonaventura
Davide
D
Romano
Arrigo F G
AF
Cicero
Pamela
P
Maffioli
D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015444:Exercise; D005215:Fasting / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D007558:Italy; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage* / Q000494:pharmacology; D000068900:Sitagliptin Phosphate; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage* / Q000494:pharmacology
D001786:Blood Glucose; D002096:C-Peptide; D002097:C-Reactive Protein; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D014230:Triazoles; C517652:hemoglobin A1c protein, human