中山大学第一附属医院李延兵主任医师团队，研究了强化简化策略治疗新诊断2型糖尿病和严重高血糖患者的疗效。相关论文于2024年10月15日发表在《英国医学杂志》上。

为了评估强化简化策略（包括短期强化胰岛素治疗（SIIT）和随后的口服抗高血糖方案）是否可以改善新诊断的2型糖尿病和严重高血糖患者的长期血糖结局，2017年12月至2020年12月，研究组在中国的15家医院进行了一项多中心、开放标签、随机试验。共招募了412例新诊断的2型糖尿病和严重高血糖（HbA_1c≥8.5%）患者。所有随机参与者最初接受SIIT治疗2-3周，随后接受利格列汀5 mg/天、二甲双胍1000 mg/天，利格列汀联合二甲双胍或单独改变生活方式（对照组）治疗48周。主要结局是SIIT后第48周达到HbA_1c<7.0%的参与者百分比。次要结局包括血糖控制、β细胞功能和胰岛素敏感性变化。

412名参与者被随机分配。基线时，平均年龄为46.8岁（标准差11.2），平均体重指数为25.8（2.9），平均HbA_1c为11.0%（1.9%）。在第48周，利格列汀联合二甲双胍组、利格列汀组和二甲双胍组分别有80%（78/97）、72%（63/88）和73%（69/95）的患者HbA_1c<7.0%，而对照组为60%（56/93）（总体P=0.02；利格列汀加二甲双胍与对照组P=0.003；利格列肽与对照组=0.12；二甲双胍与对照对照组P=0.09）。此外，利格列汀联合二甲双胍组、利格列汀组和二甲双胍组分别有70%（68/97）、68%（60/88）和68%（65/95）的患者HbA_1c<6.5%，而对照组为48%（45/93）（总体P=0.005；利格列汀加二甲双胍与对照组P=0.005；利格列汀与对照组=0.01；二甲双胍与对照对照组P=0.008；经多重比较调整后均具有显著性）。因此，与对照组相比，利格列汀联合二甲双胍组的参与者在第48周更有可能达到HbA_1c<7.0%（比值比2.78，95%置信区间1.37至5.65；P=0.005）。此外，利格列汀联合二甲双胍组在空腹血糖和β细胞功能指标方面的改善最为显著。所有治疗均耐受良好。

研究结果表明，在SIIT后使用后续口服疗法的强化简化策略，特别是利格列汀与二甲双胍的组合，可持续改善新诊断的2型糖尿病和严重高血糖患者的血糖控制和β细胞功能。这种方法为2型糖尿病临床管理的决策提供了一个有前景的方向。

附：英文原文

Title: Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial

Author: Liehua Liu, Weijian Ke, Hai Li, Fangping Li, Guanjie Fan, Jian Kuang, Jianhua Ma, Xiuwei Zhang, Bing Ji, Shu Li, Yinghong Du, Yaoming Xue, Zhaohui Lyu, Leili Gao, Shen Qu, Yongquan Shi, Li Yan, Wanping Deng, Chaoyan Xu, Peiji Dai, Lijuan Xu, Juan Liu, Xuesi Wan, Guohong Wei, Shuang Yu, Shubin Hong, Pengyuan Zhang, Zhimin Huang, Xiaopei Cao, Zhihong Liao, Haipeng Xiao, Yiming Mu, Yehuda Handelsman, Yanbing Li

Issue&Volume: 2024/10/15

Abstract:

Objective To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia.

Design Multicentre, open label, randomised trial.

Setting 15 hospitals in China between December 2017 and December 2020.

Participants 412 patients with newly diagnosed type 2 diabetes and significant hyperglycaemia (HbA1c ≥8.5%).

Interventions All randomised participants initially received SIIT for 2-3 weeks, followed by linagliptin 5 mg/day, metformin 1000 mg/day, combination linagliptin plus metformin, or lifestyle modification alone (control) for 48 weeks.

Main outcome measures The primary outcome was the percentage of participants achieving HbA1c <7.0% at week 48 after SIIT. Secondary outcomes included glycaemic control, β cell function, and variations in insulin sensitivity.

Results 412 participants were randomised. At baseline, the mean age was 46.8 (standard deviation 11.2) years, mean body mass index was 25.8 (2.9), and mean HbA1c was 11.0% (1.9%). At week 48, 80% (78/97), 72% (63/88), and 73% (69/95) of patients in the linagliptin plus metformin, linagliptin, and metformin groups, respectively, achieved HbA1c <7.0%, compared with 60% (56/93) in the control group (P=0.02 overall; P=0.003 for linagliptin plus metformin versus control; P=0.12 for linagliptin versus control; P=0.09 for metformin versus control). Additionally, 70% (68/97), 68% (60/88), and 68% (65/95) of patients in the linagliptin plus metformin, linagliptin, and metformin group, respectively, achieved HbA1c <6.5% compared with 48% (45/93) in the control group (P=0.005 overall; P=0.005 for linagliptin plus metformin versus control; P=0.01 for linagliptin versus control; P=0.008 for metformin versus control; all were significant after adjustment for multiple comparisons). Thus, compared with the control group, participants in the linagliptin plus metformin group were more likely to achieve HbA1c <7.0% at week 48 (odds ratio 2.78, 95% confidence interval 1.37 to 5.65; P=0.005). Moreover, the linagliptin plus metformin group showed the most significant improvement in fasting plasma glucose and β cell function indices. All treatments were well tolerated.

Conclusions The intense simplified strategy using subsequent oral therapies post-SIIT, especially the linagliptin plus metformin combination, sustainably improved glycaemic control and β cell function in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia. This approach offers a promising direction for decision making in the clinical management of type 2 diabetes mellitus.

DOI: 10.1136/bmj-2024-080122

Source: https://www.bmj.com/content/387/bmj-2024-080122