Type 2 diabetes (T2D) is characterized by insulin resistance (IR) and dysregulated insulin secretion. Glucagon-like peptide-1 receptor agonist liraglutide promotes insulin secretion, whereas thiazolidinedione-pioglitazone decreases IR. This study aimed to compare the efficacies of increasing insulin secretion vs decreasing IR strategies for improving myocardial perfusion, energetics, and function in T2D via an open-label randomized crossover trial. Forty-one patients with T2D (age 63 years [95% CI: 59-68 years], 27 [66%] male, body mass index 27.8 kg/m) [95% CI: 26.1-29.5 kg/m)]) without cardiovascular disease were randomized to liraglutide or pioglitazone for a 16-week treatment followed by an 8-week washout and a further 16-week treatment with the second trial drug. Participants underwent rest and dobutamine stress phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance for measuring the myocardial energetics index phosphocreatine to adenosine triphosphate ratio, myocardial perfusion (rest, dobutamine stress myocardial blood flow, and myocardial perfusion reserve), left ventricular (LV) volumes, systolic and diastolic function (mitral in-flow E/A ratio), before and after treatment. The 6-minute walk-test was used for functional assessments. Pioglitazone treatment resulted in significant increases in LV mass (96 g [95% CI: 68-105 g] to 105 g [95% CI: 74-115 g]; 0.003) and mitral-inflow E/A ratio (1.04 [95% CI: 0.62-1.21] to 1.34 [95% CI: 0.70-1.54]; 0.008), and a significant reduction in LV concentricity index (0.79 mg/mL [95% CI: 0.61-0.85 mg/mL] to 0.73 mg/mL [95% CI: 0.56-0.79 mg/mL]; = 0.04). Liraglutide treatment increased stress myocardial blood flow (1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min] to 2.08 mL/g/min [95% CI: 1.57-2.24 mL/g/min]; = 0.01) and myocardial perfusion reserve (2.40 [95% CI: 1.55-2.68] to 2.90 [95% CI: 1.83-3.18]; = 0.01). Liraglutide treatment also significantly increased the rest (1.47 [95% CI: 1.17-1.58] to 1.94 [95% CI: 1.52-2.08]; 0.00002) and stress phosphocreatine to adenosine triphosphate ratio (1.32 [95% CI: 1.05-1.42] to 1.58 [95% CI: 1.19-1.71]; = 0.004) and 6-minute walk distance (488 m [95% CI: 458-518 m] to 521 m [95% CI: 481-561 m]; 0.009). Liraglutide treatment resulted in improved myocardial perfusion, energetics, and 6-minute walk distance in patients with T2D, whereas pioglitazone showed no effect on these parameters (Lean-DM [Targeting Beta-cell Failure in Lean Patients With Type 2 Diabetes]; )

中文翻译：

---

利拉鲁肽改善 2 型糖尿病患者的心肌灌注、能量和运动耐量


2 型糖尿病 (T2D) 的特点是胰岛素抵抗 (IR) 和胰岛素分泌失调。胰高血糖素样肽 1 受体激动剂利拉鲁肽可促进胰岛素分泌，而噻唑烷二酮-吡格列酮可降低 IR。本研究旨在通过开放标签随机交叉试验，比较增加胰岛素分泌与减少 IR 策略对改善 T2D 心肌灌注、能量和功能的功效。 41 名 T2D 患者（年龄 63 岁 [95% CI：59-68 岁]，27 名 [66%] 男性，体重指数 27.8 kg/m）[95% CI：26.1-29.5 kg/m）]）没有心血管疾病的患者被随机接受利拉鲁肽或吡格列酮治疗，接受 16 周的治疗，然后进行 8 周的清除，并用第二种试验药物进一步进行 16 周的治疗。参与者接受休息和多巴酚丁胺应激磷磁共振波谱和心血管磁共振，以测量心肌能量学指数磷酸肌酸与三磷酸腺苷的比率、心肌灌注（休息、多巴酚丁胺应激心肌血流量和心肌灌注储备）、左心室（LV）容量、治疗前后的收缩和舒张功能（二尖瓣流入 E/A 比）。 6 分钟步行测试用于功能评估。吡格列酮治疗导致左心室质量（96 g [95% CI: 68-105 g]）显着增加至 105 g [95% CI: 74-115 g]；0.003）和二尖瓣流入 E/A 比（1.04 [95 % CI：0.62-1.21] 至 1.34 [95% CI：0.70-1.54]；0.008），左心室同心度指数显着降低（0.79 mg/mL [95% CI：0.61-0.85 mg/mL] 至 0.73 mg） /mL [95% CI：0.56-0.79 毫克/mL] = 0.04）。利拉鲁肽治疗使应激性心肌血流量增加（1.62 mL/g/min [95% CI: 1.19-1.75 mL/g/min]）至 2.08 mL/g/min [95% CI: 1.57-2。24毫升/克/分钟]； = 0.01) 和心肌灌注储备 (2.40 [95% CI: 1.55-2.68] 至 2.90 [95% CI: 1.83-3.18]; = 0.01)。利拉鲁肽治疗还显着增加了其余部分（1.47 [95% CI：1.17-1.58]至1.94 [95% CI：1.52-2.08]；0.00002）和应激磷酸肌酸与三磷酸腺苷的比率（1.32 [95% CI：1.05-1.42]）至 1.58 [95% CI: 1.19-1.71]；= 0.004) 和 6 分钟步行距离（488 m [95% CI: 458-518 m] 至 521 m [95% CI: 481-561 m]；0.009） 。利拉鲁肽治疗改善了 2 型糖尿病患者的心肌灌注、能量和 6 分钟步行距离，而吡格列酮对这些参数没有影响（Lean-DM [针对瘦身 2 型糖尿病患者的 Beta 细胞衰竭]；）