利拉鲁肽联合赖脯胰岛素25强化治疗新诊断2型糖尿病的远期疗效观察

Long-term efficacy of liraglutide combined with premixed insulin analogues in intensive therapy of newly-diagnosed type 2 diabetes mellitus

目的观察利拉鲁肽联合赖脯胰岛素25强化治疗新诊断2型糖尿病(T2DM)的远期疗效。方法选择糖化血红蛋白(HbA1c)≥9%的新诊断T2DM患者107例,按随机数字表法分为联合利拉鲁肽治疗组(LIRA组)55例和单纯预混速效胰岛素治疗组(INS组)52例。LIRA组予赖脯胰岛素25(起始剂量0.3～0.5U/kg)联合利拉鲁肽(0.6mg,1次/d)强化治疗;INS组予赖脯胰岛素25(起始剂量0.4～0.6U/kg)强化治疗;两组均同时联用二甲双胍1 500mg/d,治疗12周评价有效性和安全性,并随访至24、48周观察比较两组远期疗效。结果 (1)最终103例完成随访(INS组49例,LIRA组54例);两组患者治疗12周时空腹血糖(FPG)、餐后2h血糖(2hPG)、HbA1c较治疗前下降,差异均有统计学意义(均P<0.05),但两组间比较无统计学差异(P>0.05);12周时LIRA组与INS组相比体重减轻(P<0.05),2h C肽(2hCP)升高更明显(P<0.05)。(2)24周时LIRA组与INS组相比,2hPG、HbA1c、体重显著为低(P<0.05或0.01);LIRA组空腹C肽(FCP)、2hCP显著高于INS组(P<0.05或0.01)。(3)48周时LIRA组FPG、2hPG、HbA1c、体重显著低于INS组(P<0.05或0.01);而稳态模型β细胞功能指数、FCP、2hCP水平高于INS组(P<0.05或0.01);LIRA组临床缓解率(单纯2hPG临床缓解及FPG、2hPG、HbA1c均临床缓解)高于INS组(P<0.05)。结论新诊断的T2DM患者在二甲双胍加赖脯胰岛素25的基础上联合利拉鲁肽强化治疗有利于胰岛功能持续改善,维持血糖达标,延长临床缓解期,同时降低体重。

Objective To investigate the long-term efficacy of liraglutide combined with premixed insulin analogues in the intensive therapy of newly diagnosed type 2 diabetes mellitus(T2DM). Methods One hundred and three newly diagnosed T2DM patients with glycosylated hemoglobin(HbA1c)≥9% were enrolled in this open-labeled, randomized, parallel-group, treat-to-target trial. Patients were treated with metformin, and randomized to receive intensive therapy with liraglutide combined with premixed insulin analogues(LIRA group,n=54) or only premixed insulin analogues(INS group, n=49). Efficacy and safety were evaluated at wk12, wk24 and wk48. Results The fasting plasma glucose(FPG), 2-h postprandial blood glucose(2hPG), HbA1c were all significantly decreased after 12 wks of treatment in both groups(P<0.05), and there was not significantly different between two treatment groups(P >0.05);however, compared with INS group the body weight loss and 2-h postprandial C peptide(2hPC) increase in LIRA group were more markedly(P<0.05). After 24 wks of treatment, the body weight, 2hPG, HbA1c were significantly lower, and the FCP, 2hPC in LIRA group were significantly higher than those in INS group(P<0.05 or 0.01). After 48 wks of treatment the body weight, FPG, 2hPG, HbA1c were significantly lower;the HOMA-β, FCP, 2 hCP in LIRA group were significantly higher than those in the INS group. Clinical remission rate was significantly higher in the LIRA group than that in the INS group. Conclusion Liraglutide combined with premixed insulin analogues can continuously improve the pancreatic islet function, reach the blood glucose standard, extend clinical remission period, and decrease body weight for patients with newly-diagnosed type 2 diabetes mellitus.