The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China.
The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
BMJ. 2024 Oct 15;387:e080122. doi: 10.1136/bmj-2024-080122.
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.
Multicentre, open label, randomised trial.
15 hospitals in China between December 2017 and December 2020.
412 patients with newly diagnosed type 2 diabetes and significant hyperglycaemia (HbA ≥8.5%).
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.
The primary outcome was the percentage of participants achieving HbA <7.0% at week 48 after SIIT. Secondary outcomes included glycaemic control, β cell function, and variations in insulin sensitivity.
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 HbA 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 HbA <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 HbA <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 HbA <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.
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.
ClinicalTrials.gov NCT03194945.
评估强化简化策略（包括短期强化胰岛素治疗[SIIT]，随后使用口服降糖药物）是否可以改善新诊断的 2 型糖尿病伴严重高血糖患者的长期血糖控制。
多中心、开放标签、随机试验。
2017 年 12 月至 2020 年 12 月中国的 15 家医院。
412 例新诊断的 2 型糖尿病且血糖显著升高（HbA≥8.5%）的患者。
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 5mg/天、二甲双胍 1000mg/天、利格列汀联合二甲双胍或单独生活方式改变（对照组）治疗 48 周。
主要结局是 SIIT 后第 48 周 HbA<7.0%的参与者比例。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 例患者被随机分组。基线时，平均年龄为 46.8（标准差 11.2）岁，平均体重指数为 25.8（2.9），平均 HbA 为 11.0%（1.9%）。在第 48 周，利格列汀+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）的患者达到 HbA<7.0%，而对照组为 60%（56/93）（总体 P=0.02；利格列汀+二甲双胍组与对照组比较 P=0.003；利格列汀组与对照组比较 P=0.12；二甲双胍组与对照组比较 P=0.09）。此外，利格列汀+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）的患者达到 HbA<6.5%，而对照组为 48%（45/93）（总体 P=0.005；利格列汀+二甲双胍组与对照组比较 P=0.005；利格列汀组与对照组比较 P=0.01；二甲双胍组与对照组比较 P=0.008；均为调整多重比较后的显著差异）。因此，与对照组相比，利格列汀+二甲双胍组患者在第 48 周时更有可能达到 HbA<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+二甲双胍组在空腹血糖和β细胞功能指数方面的改善最为显著。所有治疗均耐受良好。
SIIT 后采用后续口服治疗的强化简化策略，尤其是利格列汀+二甲双胍联合治疗，可持续改善新诊断的 2 型糖尿病伴严重高血糖患者的血糖控制和β细胞功能。这种方法为 2 型糖尿病的临床管理决策提供了一个有前景的方向。
ClinicalTrials.gov NCT03194945。
