Carroll Orlagh U, Bidulka Patrick, Basu Anirban, Adler Amanda I, O'Neill Stephen, Briggs Andrew H, Lugo-Palacios David G, Khunti Kamlesh, Grieve Richard
Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK.
Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Diabetes Obes Metab. 2025 Aug;27(8):4181-4191. doi: 10.1111/dom.16447. Epub 2025 May 21.
To compare long-term complications for people with type 2 diabetes mellitus (T2DM) following second-line treatment in routine practice with sulphonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose co-transporter-2 inhibitors (SGLT2i) added to metformin.
We used the RAPIDS microsimulation model to predict diabetes complications over 5 years after second-line treatment initiation. We combined information on 'real-world' treatment duration in England from the Clinical Practice Research Datalink with evidence on treatment effectiveness from Randomised Controlled Trials (RCTs). We estimated between-treatment differences in the probabilities of end-stage kidney disease (ESKD), heart failure hospitalisation (HF), diabetic eye disease, myocardial infarction (MI), and lower-extremity amputation (LEA).
The predicted probabilities of complications within 5 years were lower following second-line treatment with SGLT2i compared to SU and DPP4i. The mean (95% CI) difference (reduction) in the predicted probability of ESKD following SGLT2i versus SU was -0.81% (-0.89, -0.73), and for SGLT2i versus DPP4i the corresponding difference was -0.87% (-0.95, -0.79). The reduction in the probability of HF following SGLT2i versus SU was -0.90% (-1.01, -0.80), and for SGLT2i versus DPP4i it was -0.95% (-1.06, -0.84). The corresponding differences in the probabilities of diabetic eye disease following SGLT2i versus SU were -1.41% (-1.57, -1.26), and for SGLT2i versus DPP4i was -0.44% (-0.59, -0.29). The predicted probabilities of LEA were similar across treatments. Pre-existing CVD did not modify the predicted probabilities of complications.
For a general T2DM population, second-line treatment with SGLT2i rather than SU or DPP4i can reduce the probability of complications within 5 years.
比较2型糖尿病（T2DM）患者在常规治疗中二线治疗加用磺脲类药物（SU）、二肽基肽酶-4抑制剂（DPP4i）或钠-葡萄糖协同转运蛋白-2抑制剂（SGLT2i）后长期并发症的情况。
我们使用RAPIDS微观模拟模型来预测二线治疗开始后5年内的糖尿病并发症。我们将来自临床实践研究数据链的英国“真实世界”治疗时长信息与随机对照试验（RCT）的治疗有效性证据相结合。我们估计了终末期肾病（ESKD）、心力衰竭住院（HF）、糖尿病眼病、心肌梗死（MI）和下肢截肢（LEA）发生概率的治疗组间差异。
与SU和DPP4i相比，SGLT2i二线治疗后5年内并发症的预测概率更低。SGLT2i与SU相比，ESKD预测概率的平均（95%CI）差异（降低）为-0.81%（-0.89，-0.73），SGLT2i与DPP4i相比，相应差异为-0.87%（-0.95，-0.79）。SGLT2i与SU相比，HF发生概率的降低为-0.90%（-1.01，-0.80），SGLT2i与DPP4i相比为-0.95%（-1.06，-0.84）。SGLT2i与SU相比，糖尿病眼病发生概率的相应差异为-1.41%（-1.57，-1.26），SGLT2i与DPP4i相比为-0.44%（-0.59，-0.29）。各治疗组间LEA的预测概率相似。既往心血管疾病并未改变并发症的预测概率。
对于一般T2DM人群，SGLT2i二线治疗而非SU或DPP4i可降低5年内并发症的发生概率。
