Effects of saxagliptin on β-cell stimulation and insulin secretion in patients with type 2 diabetes
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Effects of saxagliptin on β-cell stimulation and insulin secretion in patients with type 2 diabetes. / Henry, R R; Smith, Susanne; Schwartz, Saul; Mudaliar, S R; Deacon, C F; Holst, Jens Juul; Duan, R Y; Chen, R S; List, J F.
In: Diabetes, Obesity and Metabolism, Vol. 13, No. 9, 2011, p. 850-858.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Effects of saxagliptin on β-cell stimulation and insulin secretion in patients with type 2 diabetes
AU - Henry, R R
AU - Smith, Susanne
AU - Schwartz, Saul
AU - Mudaliar, S R
AU - Deacon, C F
AU - Holst, Jens Juul
AU - Duan, R Y
AU - Chen, R S
AU - List, J F
N1 - © 2011 Blackwell Publishing Ltd.
PY - 2011
Y1 - 2011
N2 - Aim: To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on ß-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes. Methods: Patients in this randomized, parallel-group, double-blind, placebo-controlled study were drug-naÏve, aged 43–69 years, with baseline haemoglobin A1c (HbA1c) 5.9–8.1%. Twenty patients received saxagliptin 5 mg once daily; 16 received placebo. Patients were assessed at baseline and week 12 by intravenous hyperglycaemic clamp (0–180 min, fasting state), and intravenous-oral hyperglycaemic clamp (180–480 min, postprandial state) following oral ingestion of 75 g glucose. Primary and secondary endpoints were percent changes from baseline in insulin secretion during postprandial and fasting states, respectively. Insulin secretion was calculated by C-peptide deconvolution. Results: After 12 weeks, saxagliptin significantly increased insulin secretion percent change from baseline during the postprandial state by an 18.5% adjusted difference versus placebo (p = 0.04), an improvement associated with increased peak plasma concentrations of intact glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. In the fasting state, saxagliptin significantly increased insulin secretion by a 27.9% adjusted difference versus placebo (p = 0.02). Saxagliptin also improved glucagon area under the curve in the postprandial state (adjusted difference -21.8% vs. placebo, p = 0.03). Conclusions: DPP-4 inhibition with saxagliptin improves pancreatic ß-cell function in postprandial and fasting states, and decreases postprandial glucagon concentration. Given the magnitude of enhancement of the insulin response in the fasting state, further study into the effect of DPP-4 inhibition on the ß-cell is warranted.
AB - Aim: To study the effect of dipeptidyl peptidase-4 (DPP-4) inhibition with saxagliptin on ß-cell function as reflected by the stimulated insulin secretion rate after an enteral glucose load in patients with type 2 diabetes. Methods: Patients in this randomized, parallel-group, double-blind, placebo-controlled study were drug-naÏve, aged 43–69 years, with baseline haemoglobin A1c (HbA1c) 5.9–8.1%. Twenty patients received saxagliptin 5 mg once daily; 16 received placebo. Patients were assessed at baseline and week 12 by intravenous hyperglycaemic clamp (0–180 min, fasting state), and intravenous-oral hyperglycaemic clamp (180–480 min, postprandial state) following oral ingestion of 75 g glucose. Primary and secondary endpoints were percent changes from baseline in insulin secretion during postprandial and fasting states, respectively. Insulin secretion was calculated by C-peptide deconvolution. Results: After 12 weeks, saxagliptin significantly increased insulin secretion percent change from baseline during the postprandial state by an 18.5% adjusted difference versus placebo (p = 0.04), an improvement associated with increased peak plasma concentrations of intact glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. In the fasting state, saxagliptin significantly increased insulin secretion by a 27.9% adjusted difference versus placebo (p = 0.02). Saxagliptin also improved glucagon area under the curve in the postprandial state (adjusted difference -21.8% vs. placebo, p = 0.03). Conclusions: DPP-4 inhibition with saxagliptin improves pancreatic ß-cell function in postprandial and fasting states, and decreases postprandial glucagon concentration. Given the magnitude of enhancement of the insulin response in the fasting state, further study into the effect of DPP-4 inhibition on the ß-cell is warranted.
KW - Adamantane
KW - Adult
KW - Aged
KW - Blood Glucose
KW - Diabetes Mellitus, Type 2
KW - Dipeptides
KW - Dipeptidyl-Peptidase IV Inhibitors
KW - Double-Blind Method
KW - Female
KW - Glucose Clamp Technique
KW - Hemoglobin A, Glycosylated
KW - Humans
KW - Insulin
KW - Insulin-Secreting Cells
KW - Male
KW - Middle Aged
KW - Treatment Outcome
U2 - 10.1111/j.1463-1326.2011.01417.x
DO - 10.1111/j.1463-1326.2011.01417.x
M3 - Journal article
C2 - 21554520
VL - 13
SP - 850
EP - 858
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 9
ER -
ID: 38186220