Patra Vasavi, Yella Venkata Ramana, Konda Venu Gopal Rao, Sayana Suresh Babu, Siripuram Chandu, Konka Srujana, Kandimalla Ramesh
Department of Pharmacology, Neelima Institute of Medical Sciences, Hyderabad, IND.
Department of Pharmacology, Government Medical College and General Hospital, Bhadradri Kothagudem, IND.
Cureus. 2025 Jun 18;17(6):e86310. doi: 10.7759/cureus.86310. eCollection 2025 Jun.
Background Type 2 diabetes mellitus (T2DM) significantly increases the risk of atherosclerotic cardiovascular disease (ASCVD), and optimal lipid control is essential for reducing major adverse cardiovascular events (MACE). However, despite the widespread use of statins, many high-risk diabetic patients fail to reach target low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as effective adjunctive agents for lipid lowering. This study was conducted to evaluate the effect of PCSK9 inhibitors on lipid profile and cardiovascular outcomes in high-risk diabetic patients. Methods A prospective, observational study was conducted at Kakatiya Medical College/Mahatma Gandhi Memorial (MGM) Hospital Warangal over 18 months. A total of 100 patients with T2DM (age, 40-75 years), having established ASCVD or multiple cardiovascular risk factors and LDL-C >100 mg/dL despite maximal statin therapy, were included. All participants received proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab 75 mg or evolocumab 140 mg subcutaneously every two weeks) in addition to standard care. Lipid profile parameters were assessed at baseline, three months, and 12 months. MACE (non-fatal myocardial infarction, stroke, or cardiovascular death) was recorded and compared with a matched historical control group (n = 100) on statin therapy alone. Results At the end of 12 months, the PCSK9 inhibitor group (n = 100) showed a significant reduction in mean LDL-C from 138.5 ± 17.6 mg/dL to 64.3 ± 12.9 mg/dL (p < 0.001). An increase in high-density lipoprotein cholesterol (HDL-C) was observed from 40.8 ± 5.3 mg/dL to 45.1 ± 5.6 mg/dL (p = 0.04), and triglycerides reduced from 178.7 ± 25.2 mg/dL to 149.5 ± 19.8 mg/dL (p < 0.01). MACE occurred in seven out of 100 patients (7%) in the PCSK9 group, compared to 16 out of 100 patients (16%) in the control group (HR: 0.41; 95% CI: 0.17-0.98; p = 0.044). Specifically, non-fatal myocardial infarction occurred in three (3%) vs. seven (7%), stroke in two (2%) vs. five (5%), and cardiovascular death in two (2%) vs. four (4%) in the PCSK9 and control groups, respectively. No serious adverse drug reactions were reported among the PCSK9 users. Conclusion PCSK9 inhibitors significantly improve lipid parameters and reduce cardiovascular event rates in high-risk diabetic patients who are inadequately controlled with statins alone. These findings support their role as an effective and safe adjunctive therapy for secondary cardiovascular prevention in diabetes.
背景 2 型糖尿病（T2DM）显著增加动脉粥样硬化性心血管疾病（ASCVD）的风险，而优化血脂控制对于降低主要不良心血管事件（MACE）至关重要。然而，尽管他汀类药物广泛使用，但许多高危糖尿病患者仍无法达到目标低密度脂蛋白胆固醇（LDL-C）水平。前蛋白转化酶枯草溶菌素/kexin 9 型（PCSK9）抑制剂已成为有效的降脂辅助药物。本研究旨在评估 PCSK9 抑制剂对高危糖尿病患者血脂谱和心血管结局的影响。
方法 在卡凯提亚医学院/瓦朗加尔圣雄甘地纪念（MGM）医院进行了一项为期 18 个月的前瞻性观察性研究。纳入 100 例 T2DM 患者（年龄 40 - 75 岁），这些患者已确诊 ASCVD 或有多种心血管危险因素，且尽管接受了最大剂量他汀治疗，LDL-C 仍>100 mg/dL。所有参与者除接受标准治疗外，还接受前蛋白转化酶枯草溶菌素/kexin 9 型（PCSK9）抑制剂（阿利西尤单抗 75 mg 或依洛尤单抗 140 mg，每两周皮下注射一次）。在基线、3 个月和 12 个月时评估血脂谱参数。记录 MACE（非致命性心肌梗死、中风或心血管死亡），并与仅接受他汀治疗的匹配历史对照组（n = 100）进行比较。
结果 在 12 个月结束时，PCSK9 抑制剂组（n = 100）的平均 LDL-C 从 138.5 ± （此处原文可能有误，推测为17.6）mg/dL 显著降至 64.3 ± （此处原文可能有误，推测为12.9）mg/dL（p < 0.001）。高密度脂蛋白胆固醇（HDL-C）从 40.8 ± 5.3 mg/dL 升至 45.1 ± 5.6 mg/dL（p = 0.04），甘油三酯从 178.7 ± 25.2 mg/dL 降至 149.5 ± 19.8 mg/dL（p < 0.01）。PCSK9 组 100 例患者中有 7 例（7%）发生 MACE，而对照组 100 例患者中有 16 例（16%）发生 MACE（风险比：0.41；95%置信区间：0.1七、0.98；p = 0.044）。具体而言，PCSK9 组和对照组中，非致命性心肌梗死分别为 3 例（3%）对 7 例（7%），中风分别为 2 例（2%）对 5 例（5%），心血管死亡分别为 2 例（2%）对 4 例（4%）。PCSK9 使用者中未报告严重不良药物反应。
结论 PCSK9 抑制剂可显著改善高危糖尿病患者的血脂参数，并降低仅用他汀治疗控制不佳的患者的心血管事件发生率。这些发现支持其作为糖尿病二级心血管预防的有效且安全的辅助治疗药物的作用。
