Blonde Lawrence, Pencek Richard, MacConell Leigh
Department of Endocrinology, Ochsner Medical Center, 1514 Jefferson Highway, 70121, New Orleans, LA, USA.
Bristol-Myers Squibb/AstraZeneca, San Diego, CA, USA.
Cardiovasc Diabetol. 2015 Feb 3;14:12. doi: 10.1186/s12933-014-0171-2.
Overweight or obesity contributes to the development of type 2 diabetes mellitus (T2DM) and increases cardiovascular risk. Exenatide, a glucagon-like peptide-1 receptor agonist, significantly reduces glycated hemoglobin (A1C) and body weight and improves cardiovascular risk markers in patients with T2DM. As weight loss alone has been shown to reduce A1C and cardiovascular risk markers, this analysis explored whether weight loss contributed importantly to clinical responses to exenatide once weekly.
A pooled analysis from eight studies of exenatide once weekly was conducted. Patients were distributed into quartiles from greatest weight loss (Quartile 1) to least loss or gain (Quartile 4). Parameters evaluated for each quartile included A1C, fasting plasma glucose (FPG), blood pressure (BP), heart rate, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, and the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
The median changes from baseline in body weight in Quartiles 1-4 were -6.0, -3.0, -1.0, and +1.0 kg, respectively. All quartiles had reductions in A1C (median changes -1.6, -1.4, -1.1, and -1.2%, respectively) and FPG (-41, -40, -31, and -25 mg/dL, respectively), with the greatest decreases in Quartiles 1 and 2. Most cardiovascular risk markers (except diastolic BP) and liver enzymes improved in Quartiles 1 through 3 and were relatively unchanged in Quartile 4. Higher rates of gastrointestinal adverse events and hypoglycemia were observed in Quartile 1 compared with Quartiles 2 through 4.
Exenatide once weekly improved glycemic parameters independent of weight change, although the magnitude of improvement increased with increasing weight loss. The greatest trend of improvement in glycemic parameters, cardiovascular risk factors including systolic BP, LDL-C, total cholesterol, and triglycerides, and in liver enzymes, was seen in the patient quartiles with the greatest reductions in body weight.
超重或肥胖会促使2型糖尿病（T2DM）的发展，并增加心血管疾病风险。艾塞那肽是一种胰高血糖素样肽-1受体激动剂，可显著降低糖化血红蛋白（A1C）和体重，并改善T2DM患者的心血管疾病风险指标。由于仅体重减轻就已显示可降低A1C和心血管疾病风险指标，因此本分析探讨了体重减轻是否对每周一次使用艾塞那肽的临床反应有重要贡献。
对八项每周一次使用艾塞那肽的研究进行了汇总分析。患者按体重减轻最多（第1四分位数）至体重减轻最少或体重增加（第4四分位数）分为四个四分位数。对每个四分位数评估的参数包括A1C、空腹血糖（FPG）、血压（BP）、心率、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇、甘油三酯以及肝酶丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）。
第1 - 4四分位数的体重相对于基线的中位数变化分别为-6.0、-3.0、-1.0和+1.0 kg。所有四分位数的A1C（中位数变化分别为-1.6%、-1.4%、-1.1%和-1.2%）和FPG（分别为-41、-40、-31和-25 mg/dL）均有所降低，第1和第2四分位数下降幅度最大。第1至第3四分位数的大多数心血管疾病风险指标（除舒张压外）和肝酶均有所改善，第4四分位数相对未变。与第2至第4四分位数相比，第1四分位数观察到更高的胃肠道不良事件和低血糖发生率。
每周一次使用艾塞那肽可改善血糖参数，且与体重变化无关，尽管改善幅度随体重减轻增加而增大。在体重减轻最多的患者四分位数中，血糖参数、包括收缩压、低密度脂蛋白胆固醇、总胆固醇和甘油三酯在内的心血管疾病风险因素以及肝酶的改善趋势最为明显。
