Macauley Mavin, Hollingsworth Kieren G, Smith Fiona E, Thelwall Peter E, Al-Mrabeh Ahmad, Schweizer Anja, Foley James E, Taylor Roy
Newcastle Magnetic Resonance Centre (M.M., K.G.H., F.E.S., P.E.T., A.A.-M., R.T.), Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE4 5PL, United Kingdom; Novartis Pharma AG (A.S.), CH-4056 Basel, Switzerland; and Novartis Pharmaceutical (J.E.F.), East Hanover, New Jersey 07936.
J Clin Endocrinol Metab. 2015 Apr;100(4):1578-85. doi: 10.1210/jc.2014-3794. Epub 2015 Feb 9.
Although dipeptidyl-peptidase-4 inhibitors exert their major action via an incretin mechanism, a favorable effect of vildagliptin on lipid metabolism remains unexplained.
The objective was to examine hepatic triglyceride levels and insulin sensitivity on vildagliptin.
This was a 6-month, randomized, double-blind, placebo-controlled trial.
This was an outpatient study at a university clinical research center.
Individuals with type 2 diabetes (n = 44) and glycated hemoglobin ≤ 7.6% on stable metformin therapy were included.
Intervention was vildagliptin 50 mg twice a day or placebo over 6 months.
Main outcome measures were hepatic triglyceride levels and insulin sensitivity.
Mean fasting liver triglyceride content decreased by 27% with vildagliptin, from 7.3 ± 1.0% (baseline) to 5.3 ± 0.9% (endpoint). There was no change in the placebo group. The between-group difference in change from baseline was significant (P = .013). Mean fasting plasma glucose concentration decreased over the study period with vildagliptin vs placebo by -1.0 mmol/L (P = .018), and there was a positive correlation between these decrements and liver triglyceride in the vildagliptin group at 3 months (r = 0.47; P = .02) and 6 months (r = 0.44; P = .03). Plasma alanine aminotransferase fell from 27.2 ± 2.8 to 20.3 ± 1.4 IU/L in the vildagliptin group (P = .0007), and there was a correlation between the decrements in alanine aminotransferase and liver triglyceride (r = 0.83; P < .0001). Insulin sensitivity during the euglycemic clamp was similar in each group at baseline (3.24 ± 0.30 vs 3.19 ± 0.38 mg/kg/min) and did not change (adjusted mean change of 0.26 ± 0.22 vs 0.32 ± 0.22 mg/kg/min; P = .86). Mean body weight decreased by 1.6 ± 0.5 vs 0.4 ± 0.5 kg in the vildagliptin and placebo groups, respectively (P = .08).
This study demonstrates that the dipeptidyl-peptidase-4 inhibitor vildagliptin brings about a clinically significant decrease in hepatic triglyceride levels during 6 months of therapy unrelated to change in body weight. There was no change in peripheral insulin sensitivity.
尽管二肽基肽酶-4抑制剂主要通过肠促胰岛素机制发挥作用，但维格列汀对脂质代谢的有益作用仍无法解释。
研究维格列汀对肝脏甘油三酯水平和胰岛素敏感性的影响。
这是一项为期6个月的随机、双盲、安慰剂对照试验。
该研究在一所大学临床研究中心的门诊进行。
纳入2型糖尿病患者（n = 44），这些患者在接受稳定的二甲双胍治疗，糖化血红蛋白≤7.6%。
干预措施为维格列汀50 mg每日两次或安慰剂，持续6个月。
主要观察指标为肝脏甘油三酯水平和胰岛素敏感性。
使用维格列汀后，空腹肝脏甘油三酯平均含量降低了27%，从7.3±1.0%（基线）降至5.3±0.9%（终点）。安慰剂组无变化。两组从基线开始的变化差异具有统计学意义（P = 0.013）。在研究期间，维格列汀组与安慰剂组相比，空腹血浆葡萄糖平均浓度降低了-1.0 mmol/L（P = 0.018），在3个月（r = 0.47；P = 0.02）和6个月（r = 0.44；P = 0.03）时，维格列汀组这些降低值与肝脏甘油三酯之间存在正相关。维格列汀组血浆丙氨酸氨基转移酶从27.2±2.8降至20.3±1.4 IU/L（P = 0.0007），丙氨酸氨基转移酶降低值与肝脏甘油三酯之间存在相关性（r = 0.83；P < 0.0001）。在基线时，每组在正常血糖钳夹期间的胰岛素敏感性相似（3.24±0.30 vs 3.19±0.38 mg/kg/min），且无变化（调整后平均变化为0.26±0.22 vs 0.32±0.22 mg/kg/min；P = 0.86）。维格列汀组和安慰剂组的平均体重分别下降了1.6±0.5 kg和0.4±0.5 kg（P = 0.08）。
本研究表明，二肽基肽酶-4抑制剂维格列汀在6个月的治疗期间可使肝脏甘油三酯水平出现具有临床意义地显著降低，且与体重变化无关。外周胰岛素敏感性无变化。
