Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.
Diabetes Care. 2017 Mar;40(3):301-308. doi: 10.2337/dc16-0836. Epub 2016 Dec 20.
To assess the mechanistic effects of the glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide and the dipeptidyl peptidase 4 (DPP-4) inhibitor sitagliptin on (exocrine) pancreatic physiology and morphology.
For this randomized, double-blind, parallel-group trial, 55 patients with type 2 diabetes treated with metformin and/or sulfonylurea agents were included. Participants received liraglutide 1.8 mg ( = 19), sitagliptin 100 mg ( = 19), or matching placebos ( = 17) once daily for 12 weeks. The primary end point was change in exocrine function (intraduodenal pancreatic fluid secretion, lipase activity, fecal elastase-1, and chymotrypsin). Secondary end points included changes in plasma enzyme concentrations and pancreatic morphology (per MRI).
No patient developed pancreatitis. Sitagliptin increased intraduodenal pancreatic fluid secretion by 16.3 mL (95% CI -0.3 to 32.9; = 0.05), whereas liraglutide did not change exocrine pancreatic function. Neither therapy increased lipase/amylase levels after 12 weeks. However, liraglutide increased lipase levels after 6 weeks (23.5 U/L [95% CI 2.1-44.8]; = 0.03) and sitagliptin increased amylase levels after 2 and 6 weeks (13.7 U/L [95% CI 3.4-23.9]; = 0.03). Both drugs increased plasma trypsinogen after 12 weeks (liraglutide: 34.6 µg/mL [95% CI 15.1-54.2], = 0.001; sitagliptin: 23.9 µg/mL [95% CI 4.9-42.9], = 0.01). Neither changed pancreatic morphology, although liraglutide tended to increase pancreatic volume (7.7 cm [95% CI -1.2 to 16.6]; 0.09). Treatment-induced volume expansion was associated with increased amylase levels.
A 12-week treatment with liraglutide or sitagliptin only resulted in a brief and modest increase of plasma pancreatic enzyme concentrations in patients with type 2 diabetes. Apart from a minimal sitagliptin-induced increase in intraduodenal fluid secretion, pancreatic exocrine function was unaffected. The long-term clinical consequences of these discrete changes require further study.
评估胰高血糖素样肽 1（GLP-1）受体激动剂利拉鲁肽和二肽基肽酶 4（DPP-4）抑制剂西他列汀对（外分泌）胰腺生理和形态的作用机制。
这项随机、双盲、平行分组试验纳入了 55 例接受二甲双胍和/或磺酰脲类药物治疗的 2 型糖尿病患者。参与者每天接受利拉鲁肽 1.8mg（=19）、西他列汀 100mg（=19）或匹配的安慰剂（=17）治疗 12 周。主要终点是外分泌功能（十二指肠内胰腺液分泌、脂肪酶活性、粪便弹性蛋白酶-1 和糜蛋白酶）的变化。次要终点包括血浆酶浓度和胰腺形态（MRI）的变化。
没有患者发生胰腺炎。西他列汀使十二指肠内胰腺液分泌增加 16.3ml（95%CI-0.3 至 32.9；=0.05），而利拉鲁肽未改变外分泌胰腺功能。两种治疗方法在 12 周后均未增加脂肪酶/淀粉酶水平。然而，利拉鲁肽在 6 周后增加了脂肪酶水平（23.5U/L [95%CI 2.1-44.8]；=0.03），西他列汀在 2 周和 6 周后增加了淀粉酶水平（13.7U/L [95%CI 3.4-23.9]；=0.03）。两种药物在 12 周后均增加了血浆胰蛋白酶原（利拉鲁肽：34.6μg/ml [95%CI 15.1-54.2]，=0.001；西他列汀：23.9μg/ml [95%CI 4.9-42.9]，=0.01）。两种药物均未改变胰腺形态，尽管利拉鲁肽有增加胰腺体积的趋势（7.7cm [95%CI-1.2 至 16.6]；=0.09）。治疗诱导的体积扩张与淀粉酶水平升高有关。
在 2 型糖尿病患者中，利拉鲁肽或西他列汀治疗 12 周仅导致血浆胰腺酶浓度短暂适度升高。除了西他列汀引起的十二指肠内液体分泌略有增加外，胰腺外分泌功能不受影响。这些离散变化的长期临床后果需要进一步研究。
