Journal of diabetes · 2014
Different effects of two dipeptidyl peptidase-4 inhibitors and glimepiride on β-cell function in a newly designed two-step hyperglycemic clamp.
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhang Yifei, Chi Jie, Wang Weiqing, Hong Jie, Gu Weiqiong, Wang Bokai, Ning Guang
Аннотация
BACKGROUND: Dipeptidyl peptidase (DPP)-4 inhibitors and sulfonylureas may have different effects on islet function. We designed a new two-step hyperglycemic clamp to further compare the effects of sitagliptin, saxagliptin, and glimepiride on β-cell function and the incretin effect.
METHODS: The present study was a four-way cross-over open label randomized study. Twelve healthy male subjects were administered a single dose of sitagliptin (100 mg), saxagliptin (5 mg), glimepiride (2 mg) or blank control 2 h before undergoing a two-step hyperglycemic clamp (Step 1: only intravenous glucose was administered; Step 2: i.v. glucose loading was combined with oral glucose consumption). Two-phase insulin secretion, glucagon secretion, and incretin levels were measured during the clamp.
RESULTS: In Step 1, with i.v. glucose only, there were no differences between the effects of the three drugs on insulin secretion, except that saxagliptin increased second-phase insulin secretion more than glimepiride (P = 0.007). In Step 2, oral glucose consumption led to an approximate two fold increase in insulin secretion and both gliptins significantly increased first-phase insulin secretion compared with glimepiride (P = 0.003 for both). Saxagliptin further increased second-phase insulin secretion compared with glimepiride (P = 0.005) and sitagliptin (P < 0.001). Both gliptins significantly decreased glucagon secretion and increased active glucagon-like peptide-1 (GLP-1) compared with glimepiride, especially in Step 2.
CONCLUSIONS: The two-step hyperglycemic clamp appears to be a precise method to assess β-cell function by taking the effect of incretins into consideration. The oral glucose consumption adds to the i.v. glucose infusion, amplifying the differences in the effects of DPP-4 inhibitors and glimepiride on insulin secretion.
METHODS: The present study was a four-way cross-over open label randomized study. Twelve healthy male subjects were administered a single dose of sitagliptin (100 mg), saxagliptin (5 mg), glimepiride (2 mg) or blank control 2 h before undergoing a two-step hyperglycemic clamp (Step 1: only intravenous glucose was administered; Step 2: i.v. glucose loading was combined with oral glucose consumption). Two-phase insulin secretion, glucagon secretion, and incretin levels were measured during the clamp.
RESULTS: In Step 1, with i.v. glucose only, there were no differences between the effects of the three drugs on insulin secretion, except that saxagliptin increased second-phase insulin secretion more than glimepiride (P = 0.007). In Step 2, oral glucose consumption led to an approximate two fold increase in insulin secretion and both gliptins significantly increased first-phase insulin secretion compared with glimepiride (P = 0.003 for both). Saxagliptin further increased second-phase insulin secretion compared with glimepiride (P = 0.005) and sitagliptin (P < 0.001). Both gliptins significantly decreased glucagon secretion and increased active glucagon-like peptide-1 (GLP-1) compared with glimepiride, especially in Step 2.
CONCLUSIONS: The two-step hyperglycemic clamp appears to be a precise method to assess β-cell function by taking the effect of incretins into consideration. The oral glucose consumption adds to the i.v. glucose infusion, amplifying the differences in the effects of DPP-4 inhibitors and glimepiride on insulin secretion.