OBJECTIVE: The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation remain obscure. The aim of this study was to evaluate the effects of the addition of sitagliptin on the β-cell function and various inflammatory biomarkers in type 2 diabetic patients. METHODS: After a run-in period of taking metformin, 178 diabetic patients with poor glycemic control were randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in addition to metformin for 12 months. We evaluated the following parameters at three, six, nine and twelve months: body mass index (BMI), glycemic control, the homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis model assessment β-cell function index (HOMA-β), the proinsulin/fasting plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin, omentin-1 and tumor necrosis factor-α (TNF-α). Before and twelve months after the addition of sitagliptin, the patients underwent combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation to assess insulin sensitivity and secretion. RESULTS: Treatment with sitagliptin + metformin was more effective than placebo + metformin in improving glycemic control, the HOMA-IR and the glucagon level and increasing the HOMA-β and all β-cell measurements after combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation. Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin. CONCLUSION: When treatment with metformin alone is not adequate for obtaining glycemic control, the addition of sitagliptin can be considered due to its actions in preserving the β-cell function and reducing the levels of biomarkers of inflammation.
RCT Entities:
OBJECTIVE: The effects of dipeptidyl peptidase-4 (DPP-4) inhibition on adipose tissue inflammation remain obscure. The aim of this study was to evaluate the effects of the addition of sitagliptin on the β-cell function and various inflammatory biomarkers in type 2 diabeticpatients. METHODS: After a run-in period of taking metformin, 178 diabeticpatients with poor glycemic control were randomized to take sitagliptin at a dose of 100 mg once a day or a placebo in addition to metformin for 12 months. We evaluated the following parameters at three, six, nine and twelve months: body mass index (BMI), glycemic control, the homeostasis model assessment insulin resistance index (HOMA-IR), the homeostasis model assessment β-cell function index (HOMA-β), the proinsulin/fasting plasma insulin ratio (Pr/FPI ratio) and the levels of fasting plasma insulin (FPI), fasting plasma proinsulin (FPPr), C-peptide, glucagon, resistin, vaspin, omentin-1 and tumor necrosis factor-α (TNF-α). Before and twelve months after the addition of sitagliptin, the patients underwent combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation to assess insulin sensitivity and secretion. RESULTS: Treatment with sitagliptin + metformin was more effective than placebo + metformin in improving glycemic control, the HOMA-IR and the glucagon level and increasing the HOMA-β and all β-cell measurements after combined euglycemic hyperinsulinemic and hyperglycemic clamping with subsequent arginine stimulation. Regarding inflammatory biomarkers, sitagliptin + metformin more effectively reduced the levels of resistin, vaspin and omentin-1 than placebo + metformin. CONCLUSION: When treatment with metformin alone is not adequate for obtaining glycemic control, the addition of sitagliptin can be considered due to its actions in preserving the β-cell function and reducing the levels of biomarkers of inflammation.
Authors: Subodh Verma; Ronald M Goldenberg; Deepak L Bhatt; Michael E Farkouh; Adrian Quan; Hwee Teoh; Kim A Connelly; Lawrence A Leiter; Jan O Friedrich Journal: CMAJ Open Date: 2017-02-24