二肽基肽酶-4抑制剂（DPP-4I），肠促胰岛素激素作用的关键调节剂，在2型糖尿病（T2DM）患者中发挥抗高血糖作用。一个主要的悬而未决的问题涉及DPP-4I改善非酒精性脂肪性肝病（NAFLD）患者肝内脂质（IHL）含量的潜在能力。这项研究的目的是评估西格列汀对NAFLD患者IHL的影响。
有前景的,24周,单中心,开放标签，比较研究纳入68例中国T2DMNAFLD患者。受试者随机分为4组：对照组（14例），不服药；西格列汀组（17例），接受西格列汀治疗（100mg/天）；二甲双胍组（500mg/天3次）（17例）；西格列汀联合二甲双胍组，接受西格列汀（100mg/天）和二甲双胍（500mg/天3次）。IHL,体检(腰部情况，WC；体重指数，BMI），糖脂代谢(空腹血糖，FPG;血红蛋白A1c,Hb1A1c;甘油三酯;胆固醇;丙氨酸转氨酶,ALT；天冬氨酸转氨酶，AST)在基线和24周时测量。
1)除对照组外,各组WC和BMI均显著降低(P均<0.05)。2）西格列汀之间的IHL无统计学差异，二甲双胍,西格列汀联合二甲双胍组治疗前后比较(均P>0.05)。仅二甲双胍组治疗前后IHL差异有统计学意义(P<0.05)。3)与对照组相比,西格列汀治疗后FBG和HbA1c显著下降(均P<0.01)。此外,与二甲双胍组相比，西格列汀组HhA1c显著降低（P<0.05）。4）HbA1c和FBG分别降低0.8％和0.7mmol/l，使用西格列汀治疗的HbA1c低于7％的患者百分比为65％。
西格列汀改善葡萄糖代谢异常，但不能降低患有NAFLD的T2DM中的IHL，表明西格列汀可能是间接治疗NAFLD的一种治疗选择，而不是直接治疗IHL。临床试验注册：https://clinicaltrials.gov/,标识符CTR#NCT05480007。
Dipeptidyl peptidase-4 inhibitors (DPP-4I), key regulators of the actions of incretin hormones, exert anti-hyperglycemic effects in type 2 diabetes mellitus (T2DM) patients. A major unanswered question concerns the potential ability of DPP-4I to improve intrahepatic lipid (IHL) content in nonalcoholic fatty liver disease (NAFLD) patients. The aim of this study was to evaluate the effects of sitagliptin on IHL in NAFLD patients.
A prospective, 24-week, single-center, open-label, comparative study enrolled 68 Chinese NAFLD patients with T2DM. Subjects were randomly divided into 4 groups: control group who did not take medicine (14 patients); sitagliptin group who received sitagliptin treatment (100mg per day) (17 patients); metformin group who received metformin (500mg three times per day) (17 patients); and sitagliptin plus metformin group who received sitagliptin (100mg per day) and metformin (500 mg three times per day) (20 patients). IHL, physical examination (waist circumstances, WC; body mass index, BMI), glucose-lipid metabolism (fasting plasma glucose, FPG; hemoglobin A1c, Hb1A1c; triglycerides; cholesterol; alanine aminotransferase, ALT; aspartate aminotransferase, AST) were measured at baseline and at 24 weeks.
1) WC and BMI were decreased significantly in all groups except control group (all P<0.05). 2) There was no statistically significant difference in IHL among the sitagliptin, metformin, and sitagliptin plus metformin groups before and after treatment(all P>0.05). Only the metformin group showed a statistically significant difference in IHL before and after treatment(P<0.05). 3) Sitagliptin treatment led to a significant decrease in FBG and HbA1c when compared with the control group (all P<0.01). Additionally, HhA1c was significant decreased in the sitagliptin group when compared with the metformin group (P< 0.05). 4) HbA1c and FBG were decreased by 0.8% and 0.7 mmol/l respectively and the percentage of patients with HbA1c less than 7% was 65% with sitagliptin treatment.
Sitagliptin improves abnormalities in glucose metabolism, but not reduces the IHL in T2DM with NAFLD, indicating that sitagliptin might be a therapeutic option for treatment of NAFLD indirectly while not directly on IHL. Clinical Trial Registration: https://clinicaltrials.gov/, identifier CTR# NCT05480007.
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