Efficacy and safety of liraglutide 3.0 mg for weight management are similar across races: subgroup analysis across the SCALE and phase II randomized trials

The efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to diet and exercise, was evaluated in racial subgroups. This post hoc analysis of pooled data from five double‐blind randomized, placebo‐controlled trials was conducted in 5325 adults with either a body mass index (BMI) ≥27 kg/m² plus ≥1 comorbidity or a BMI ≥30 kg/m². Statistical interaction tests evaluated possible treatment effect differences between racial subgroups: white (4496, 84.4%), black/African‐American (550, 10.3%), Asian (168, 3.2%) and other (111, 2.1%). Effects of liraglutide 3.0 mg on weight loss, associated metabolic effects and safety profile were generally consistent across racial subgroups. All achieved statistically significant mean weight loss at end‐of‐treatment with liraglutide 3.0 mg versus placebo: white 7.7% versus 2.3%, black/African‐American 6.3% versus 1.4%, Asian 6.3% versus 2.5%, other 7.3% versus 0.49%. Treatment effects on weight and cardiovascular risk markers generally showed no dependence on race (interaction test p > 0.05). Adverse events were similar across racial subgroups.     

Comparative effects of liraglutide 3 mg vs structured lifestyle modification on body weight,liver fat and liver function in obese patients with non‐alcoholic fatty liver disease: A pilot randomized trial

We compared the effects of weight loss induced by the glucagon‐like peptide 1‐agonist liraglutide with a structured lifestyle intervention in obese adults with non‐alcoholic fatty liver disease (NAFLD). Obese (body mass index ≥30 kg/m², mean weight 96.0 ± 16.3 kg) non‐diabetic Asian adults, with NAFLD diagnosed by liver fat fraction (LFF) ≥ 5.5% on magnetic resonance imaging without other causes of hepatic steatosis, were randomized to a supervised program of dieting (restriction by 400 kilocalories/d) plus moderate‐intensity aerobic exercise (~200 min/wk; DE group, n = 12), or liraglutide at the 3 mg daily dose approved for weight loss (LI group, n = 12), for 26 weeks. Both DE and LI groups had significant (P < .01) and similar reductions in weight (?3.5 ± 3.3 vs ?3.5 ± 2.1 kg, respectively, P = .72), LFF (?8.9 ± 13.4 vs ?7.2% ± 7.1%, P = .70), serum alanine aminotransferase (?42 ± 46 vs ?34 ± 27 U/L, P = .52) and aspartate aminotransferase (?23 ± 24 vs ?18 ± 15 U/L, P = .53). In this first randomized study comparing the 2 weight‐loss modalities for improving NAFLD, liraglutide was as effective as structured lifestyle modification.     

Glucagon‐like peptide‐1 receptor agonists and risk of acute pancreatitis in patients with type 2 diabetes

Glucagon‐like peptide‐1 receptor agonist (GLP‐1RAs) labels warn about acute pancreatitis (AP) and impose upon doctors the obligation to inform patients about symptoms of AP. Here we systematically reviewed the risk of AP in randomized placebo‐controlled trials (RCTs) investigating the effect of GLP‐1RAs in type 2 diabetes. We performed a systematic review with meta‐analysis of long‐term (minimum 24 months), placebo‐controlled GLP‐1RA RCTs in which AP was a predefined adverse event and adjudicated by blinded and independent adjudicating committees. Three high‐quality RCTs included a total of 9347 GLP‐1RA‐treated and 9353 placebo‐treated patients with type 2 diabetes. Compared to placebo, treatment with GLP1‐RA was not associated with increased risk of AP (Peto odds ratio 0.745 [95% CI, 0.47‐1.17]). Trial Sequential Analysis suggested that additional evidence is needed. In conclusion, this review found no evidence that treatment with GLP‐1RA increases the risk of AP in patients with type 2 diabetes.     

利拉鲁肽的药理及临床研究进展

 利拉鲁肽是一种酰化胰高血糖素样肽-1（GLP-1）类似物,通过激活GLP-1受体,以葡萄糖依赖性刺激胰岛素分泌并抑制胰高血糖素分泌,临床用于2型糖尿病的二线治疗,可与其他口服降糖药联合使用,但不用于1型糖尿病的治疗。文中通过Medline对利拉鲁肽进行文献检索,并对其药理作用、药动学、临床研究、安全性和药物相互作用等进行综述。     

利拉鲁肽和西格列汀在治疗2型糖尿病中的长期益处对比

目的：比较利拉鲁肽和西格列汀在治疗中国2型糖尿病（T2DM）患者中的长期临床和成本益处。方法：数据来源于一项随机对照试验（NCT02008682）,2型糖尿病患者随机分为注射利拉鲁肽1.2 mg·d^-1和口服西格列汀100 mg·d^-1。根据已发表和验证的CORE糖尿病模型,对临床结果和直接费用进行长期预测。未来成本和临床结果的贴现率为每年0%和5%。并进行敏感性分析。结果：与西格列汀相比,使用利拉鲁肽的预期寿命（14.12年 vs. 13.89年）和健康调整生命年[9.11 vs. 8.91（QALYs）]延长,并通过有效控制血糖,减少了肾病、心血管疾病、眼科、糖尿病足等相关并发症的发生。利拉鲁肽1.2 mg比西他列汀的增量成本效益比增加了72 101元/QALY。敏感性分析结果表明,使用利拉鲁肽的QALY和治疗成本均高于西格列汀,并且改善的血糖控制可能是临床获益的主要影响因素。结论：利拉鲁肽加入二甲双胍单药治疗可以改善健康调整生命年,是治疗T2DM的一种经济有效的方法。     

利拉鲁肽注射液治疗超重及肥胖的2型糖尿病伴微量白蛋白尿患者的临床研究

目的观察利拉鲁肽注射液对超重及肥胖的2型糖尿病(T2DM)伴微量白蛋白尿患者的肾功能及胰岛功能的影响。方法将116例超重及肥胖的T2DM伴微量白蛋白尿患者随机分为对照组和试验组,每组58例。对照组予以二甲双胍每次1.0 g,bid,口服;试验组在对照组治疗的基础上,予以利拉鲁肽,起始剂量每次0.6 mg,1周后加量至每次1.2 mg,qd,皮下注射。2组患者均治疗3个月。比较2组患者的血糖状况[空腹血糖(FPG)、糖化血红蛋白(Hb A1C)、餐后2 h血糖(2 h PG)]、肾功能[24 h尿白蛋白排泄率(UAER)、血清肌酸酐(SCr)、血尿酸(SUA)、尿微量白蛋白/尿肌酸酐(ACR)]、胰岛功能[胰岛素抵抗指数(HOMA-IR)、胰岛β细胞功能指数(HOMA-β)、空腹胰岛素(FINS)]、炎症状态[肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-1],以及药物不良反应的发生情况。结果治疗后,试验组和对照组的FPG分别为(6.27±0.81)和(7.64±1.68)mmol·L^-1,Hb A1C分别为(6.31±0.97)%和(7.18±0.95)%,2 h PG分别为(7.39±1.08)和(8.33±1.56)mmol·L^-1,UAER分别为(101.60±39.55)和(126.64±42.01)mg/24 h,SCr分别为(76.91±21.52)和(94.03±28.41)μmol·L^-1,SUA分别为(222.22±34.10)和(256.69±41.35)μmol·L^-1,ACR分别为(5.30±1.38)和(7.60±2.08)mg·mmol^-1,HOMA-IR分别为3.23±0.54和4.36±0.73,HOMA-β分别为49.21±10.38和32.93±15.75,FINS分别为(9.39±1.47)和(7.68±0.82)μU·mL^-1,TNF-α分别为(40.42±11.40)和(54.09±13.98)pg·m L^-1,IL-6分别为(24.30±9.25)和(30.90±12.43)pg·m L^-1,IL-1分别为(42.34±7.07)和(56.26±8.23)pg·mL^-1,差异均有统计学意义(均P<0.05)。试验组的药物不良反应以胃肠道反应和低血糖为主,对照组的药物不良反应以低血糖为主。试验组和对照组的总药物不良反应发生率分别为20.69%和3.45%,差异有统计学意义(P<0.01)。结论利拉鲁肽注射液有利于改善超重及肥胖的T2DM伴微量白蛋白尿的肾功能和胰岛功能,但胃肠道相关的药物不良反应发生率较高。     

Sgemaglutide in type 2 diabetes – is it the best glucagon-like peptide 1 receptor agonist (GLP-1R agonist)?

Introduction: Glucagon-like peptide-1 (GLP-1) is produced by the gut, and in a glucose-dependent manner stimulates insulin secretion while inhibiting glucagon secretion, reduces appetite and energy intake, and delays gastric emptying. The GLP-1R agonist semaglutide has recently been registered to treat type 2 diabetes.

Area covered: This review is of semaglutide in type 2 diabetes, and considers which properties of this GLP-1R agonist, may be responsible for its clinical outcome benefits .

Expert opinion: The pharmacokinetics of semaglutide make it ideal for once-weekly dosing. SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) showed that semaglutide 0.5 or 1 mg subcutaneously once-weekly reduced cardiovascular outcomes in subjects with type 2 diabetes and cardiovascular disease or risk, mean age 65 years, baseline HbA1c 8.7% and mean body weight of 92 kg. Although, semaglutide may be a useful drug in this population, it increased retinopathy to a small extent and this needs further investigation. Also, it is not known whether semaglutide will improve cardiovascular outcomes in other populations including those with lower ages, HbA1c values, and body weights similar to those included in the unsuccessful clinical outcome trials with the GLP-1R agonists, lixisenatide and exenatide.     

利拉鲁肽对2型糖尿病患者胰岛素抵抗的影响

目的探讨利拉鲁肽联合二甲双胍与单纯使用二甲双胍对2型糖尿病患者胰岛素抵抗的影响。方法收集30例2型糖尿病患者(使用利拉鲁肽联合二甲双胍治疗)为试验组,收集30例2型糖尿病患者(单纯使用二甲双胍治疗)为对照组,比较两组治疗前及治疗后3个月糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)、血清脂联素、一氧化氮(NO)、内皮素(ET)水平变化情况。结果试验组HbA1c、HOMA-IR、NO、ET水平下降程度,以及血清脂联素水平上升程度均较对照组明显,差异均有统计学意义(P0.05)。结论利拉鲁肽较二甲双胍对2型糖尿病患者改善胰岛素抵抗的效果更为明显。