Berkovic Maja Cigrovski, Bilic-Curcic Ines, Herman Mahecic Davorka, Gradiser Marina, Grgurevic Mladen, Bozek Tomislav
Department for Endocrinology, Diabetes and Metabolism University Hospital Centre, Sestre Milosrdnice, Zagreb, Croatia.
Department of Pharmacology, Faculty of Medicine, J.J. Strossmayer University Osijek, Clinical Hospital Center Osijek, Osijek, Croatia.
Diabetes Ther. 2017 Dec;8(6):1297-1308. doi: 10.1007/s13300-017-0324-x. Epub 2017 Oct 26.
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are recommended therapy for type 2 diabetes (T2DM) and liraglutide is the most used worldwide. We assessed the glycemic efficacy and extra-glycemic effects of liraglutide during 36 months' follow-up of individuals with poorly regulated T2DM under routine clinical practice and sought to identify the phenotype of treatment responders.
A total of 207 individuals were included. The primary endpoint was the proportion of participants with HbA1c < 7.0% and/or weight reduction. Secondary endpoints included changes in lipids, blood pressure, fasting c-peptide, and antidiabetic treatment during follow-up of 3 years.
Liraglutide was prescribed to 89.8% of participants already on at least two antidiabetic medications and 18% on insulin. Subject's mean age was 53.28 ± 9.42 years with duration of diabetes 8.29 ± 4.89 years. Baseline HbA1c was 8.5 ± 1.3% and body mass index (BMI) was 39 ± 4.5 kg/m. Reduction of HbA1c was observed in 84.4% of participants, and 89.2% experienced average weight reduction of 5 kg. A composite outcome (reduction of HbA1c with any weight loss) was achieved in 76.2% of patients. After 6 months on liraglutide treatment, 38.1% of participants achieved target HbA1c level < 7%. This effect was maintained for 36 months in 50.8% of subjects. Increase in c-peptide was evident after 24 months (p = 0.030). Participants experienced a significant reduction in systolic blood pressure (BP) (p = 0.003), while there was no effect on diastolic BP, lipid profile, or liver enzymes. The number of participants treated with sulfonylurea decreased from 60.8% to 17.5%, while the number treated with insulin and sodium-glucose co-transporter-2 (SGLT-2) inhibitor increased (17.6% to 24.6% and 2.5% to 36.8%, respectively). Independent predictors of durability of HbA1c reduction were initial BMI (p = 0.004), HbA1c (p < 0.001), systolic BP (p = 0.007), and cholesterol (p = 0.020). Moreover, female gender and shorter duration of diabetes were independent predictors for HbA1c reduction.
Liraglutide shows sustained glycemic and extra-glycemic effects when used for treatment of obese poorly regulated individuals with T2DM.
胰高血糖素样肽-1（GLP-1）受体激动剂（RAs）是2型糖尿病（T2DM）的推荐治疗药物，利拉鲁肽是全球使用最广泛的一种。我们在常规临床实践中对血糖控制不佳的T2DM患者进行了36个月的随访，评估了利拉鲁肽的血糖疗效和血糖外效应，并试图确定治疗反应者的表型。
共纳入207名个体。主要终点是糖化血红蛋白（HbA1c）<7.0%和/或体重减轻的参与者比例。次要终点包括3年随访期间血脂、血压、空腹C肽和抗糖尿病治疗的变化。
89.8%已服用至少两种抗糖尿病药物的参与者以及18%使用胰岛素的参与者接受了利拉鲁肽治疗。受试者的平均年龄为53.28±9.42岁，糖尿病病程为8.29±4.89年。基线HbA1c为8.5±1.3%，体重指数（BMI）为39±4.5kg/m²。84.4%的参与者HbA1c有所降低，89.2%的参与者平均体重减轻了5kg。76.2%的患者实现了综合结局（HbA1c降低且伴有体重减轻）。利拉鲁肽治疗6个月后，38.1%的参与者达到了目标HbA1c水平<7%。50.8%的受试者在36个月内维持了这一效果。24个月后C肽明显升高（p=0.030）。参与者的收缩压（BP）显著降低（p=0.003），而对舒张压、血脂谱或肝酶无影响。接受磺脲类药物治疗的参与者人数从60.8%降至17.5%，而接受胰岛素和钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂治疗的人数增加（分别从17.6%增至24.6%和从2.5%增至36.8%）。HbA1c降低持久性的独立预测因素为初始BMI（p=0.004）、HbA1c（p<0.001）、收缩压（p=0.007）和胆固醇（p=0.020）。此外，女性性别和较短的糖尿病病程是HbA1c降低的独立预测因素。
利拉鲁肽用于治疗肥胖且血糖控制不佳的T2DM患者时，显示出持续的血糖和血糖外效应。
