University of Liverpool, Liverpool, UK.
London School of Hygiene and Tropical Medicine, London, UK.
BMC Med. 2018 Jul 16;16(1):116. doi: 10.1186/s12916-018-1085-8.
Intensification of metformin monotherapy with additional glucose-lowering drugs is often required in patients with type 2 diabetes (T2D). This study evaluated changes in HbA1c and weight, as well as treatment persistence, associated with different second-line therapies used in UK clinical practice.
The UK Clinical Practice Research Datalink was used to identify patients with T2D who initiated second-line therapy after metformin monotherapy between 1 August 2013 and 14 June 2016. Treatment persistence and changes in HbA1c and weight were assessed at 6-month intervals up to 18 months.
In total, 9097 patients (mean age 61.2 years, 57.2% men, mean [standard deviation] HbA1c 9.0% [1.8]/ 75 mmol/mol [19.7]) were included in the analysis, with a median 2.3 years between initiating metformin monotherapy and initiating second-line therapy. Patients were stratified according to second-line therapy: metformin in combination with sulfonylurea (SU; n = 4655 [51.2%]), a dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor; n = 2899 [31.9%]), or a sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor; n = 441 [4.9%]) or other therapies (all other second-line treatments; n = 1102 [12.1%]). At 18 months, the cumulative proportion of patients changing treatment was lowest for those who received metformin plus an SGLT-2 inhibitor (42.3%), followed by patients on metformin plus SU or metformin plus a DPP-4 inhibitor (46.8%). HbA1c reductions were seen with all second-line therapies, with an overall mean (standard error) reduction of -1.23% (0.05)/-13.4 mmol/mol (0.5). Changes were directly, but not linearly, related to baseline HbA1c and were greater in those with higher HbA1c at baseline. Weight loss from baseline was greatest in patients treated with metformin plus either an SGLT-2 inhibitor (-4.2 kg) or a DPP-4 inhibitor (-1.5 kg). The highest proportion of patients who achieved the composite outcome of HbA1c reduction ≥ 0.5%, body weight loss ≥ 2.0 kg and treatment persistence for 18 months was observed in those receiving metformin plus an SGLT-2 inhibitor (36.5%).
In this population-based cohort, all second-line therapies added to metformin monotherapy improved glycaemic control, but the lowest treatment change/discontinuation rate and most sustained weight loss was seen with patients receiving metformin plus an SGLT-2 inhibitor.
2 型糖尿病（T2D）患者常需要将二甲双胍单药治疗强化，联合使用其他降糖药物。本研究评估了在英国临床实践中使用的不同二线治疗方法与 HbA1c 和体重的变化以及治疗的持久性之间的关系。
利用英国临床实践研究数据链接，确定了 2013 年 8 月 1 日至 2016 年 6 月 14 日期间，在接受二甲双胍单药治疗后开始二线治疗的 T2D 患者。每 6 个月评估一次治疗的持久性以及 HbA1c 和体重的变化，直至 18 个月。
共纳入 9097 例患者（平均年龄 61.2 岁，57.2%为男性，平均[标准差]HbA1c 9.0%[1.8]/75mmol/mol[19.7]），在开始二甲双胍单药治疗和开始二线治疗之间的中位时间为 2.3 年。根据二线治疗方案将患者分层：二甲双胍联合磺酰脲类药物（SU；n=4655[51.2%]）、二肽基肽酶-4 抑制剂（DPP-4 抑制剂；n=2899[31.9%]）、钠-葡萄糖共转运蛋白 2 抑制剂（SGLT-2 抑制剂；n=441[4.9%]）或其他治疗（所有其他二线治疗；n=1102[12.1%]）。在 18 个月时，接受二甲双胍加 SGLT-2 抑制剂治疗的患者中，改变治疗方案的累积比例最低（42.3%），其次是接受二甲双胍加 SU 或二甲双胍加 DPP-4 抑制剂治疗的患者（46.8%）。所有二线治疗均能降低 HbA1c，总体平均（标准误差）降幅为-1.23%（0.05）/-13.4mmol/mol（0.5）。HbA1c 的降低与基线 HbA1c 呈直接但非线性关系，且基线 HbA1c 较高的患者降幅更大。与基线相比，体重减轻最多的是接受二甲双胍加 SGLT-2 抑制剂（-4.2kg）或 DPP-4 抑制剂（-1.5kg）治疗的患者。接受二甲双胍加 SGLT-2 抑制剂治疗的患者中，达到 HbA1c 降低≥0.5%、体重减轻≥2.0kg 和治疗持续 18 个月的复合结局的患者比例最高（36.5%）。
在本基于人群的队列研究中，联合二甲双胍单药治疗的所有二线治疗均改善了血糖控制，但治疗变化/停药率最低和体重持续下降的患者是接受二甲双胍加 SGLT-2 抑制剂治疗的患者。
