Pleiotropic effects of liraglutide in patients with type 2 diabetes and moderate renal impairment: Individual effects of treatment

Liraglutide has pleiotropic effects favouring cardiovascular and renal risks. We investigated individual responses to liraglutide in six cardio-renal risk factors to examine whether responses in one risk factor are associated with changes in other risk factors (cross-dependency). We performed secondary analysis of the LIRA-RENAL trial (n = 279) in type 2 diabetes. HbA1c, body weight, systolic blood pressure (SBP)_, low density lipoprotein (LDL)-cholesterol, urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were measured at baseline and after 26 weeks of liraglutide/placebo treatment: “Good responders” had a change within the best quartile. In the liraglutide-treated group, good HbA1c responders showed similar changes in other risk factors analysed to low responders (P ≥ 0.17). Good body weight responders had a larger reduction in HbA1c than low body weight responders (−1.6 ± 0.94 vs. –1.0 ± 0.82%; P = 0.003), but similar changes in the other risk factors (P ≥ 0.11). Good and low responders in SBP, UACR, LDL-cholesterol or eGFR showed similar changes in other risk factors (P ≥ 0.07). Treatment response to liraglutide is largely individual; aside from an association between body weight and HbA1c reduction, there are no obvious cross-dependencies in risk factor response.     

Fixed combination of insulin and a glucagon-like peptide-1 analog for the treatment of type 2 diabetes,exemplified by insulin degludec and liraglutide

Insulin therapy in the management of Type 2 diabetes is often postponed and/or not adequately intensified to maintain glycemic control because of the risk of weight gain and hypoglycemia. A fixed combination of the long-acting insulin degludec and liraglutide has recently been accepted by the EMA for the management of Type 2 diabetes. The incentive for this combination is to exploit the advantages of each of the drugs while counterbalancing the side effects. Insulin degludec effectively reduces fasting plasma glucose, but carries the risk of hypoglycemia and body weight gain. Liraglutide, on the other hand, exerts glycemic control with a minimal risk of hypoglycemia and, at the same time, reduces appetite and body weight.     

Overview of new antiobesity drugs

A short overview of new drugs approved for the treatment of obesity (lorcaserin, phentermine/topiramate combination) as well as those with a perspective for approval as antiobesity drugs (cetilistat, naltrexone/bupropion combination, liraglutide) is presented. All these drugs produce significant weight loss accompanied by reductions in cardiometabolic health risks. Although the adverse events were rather rare and tended to decrease with the duration of treatment with most of these medications, the drug-specific safety concerns should be seriously considered. In order to ensure an appropriate, efficient and safe implementation of novel antiobesity drugs into the comprehensive treatment of obesity, it will be necessary to establish a network of physicians and other health-care providers well educated in obesity management.     

Efficacy and safety of liraglutide,a once‐daily human glucagon‐like peptide‐1 analogue,in Latino/Hispanic patients with type 2 diabetes: post hoc analysis of data from four phase III trials

The aim of the present analysis was to evaluate the efficacy of the glucagon‐like peptide‐1 receptor agonist liraglutide in Latino/Hispanic individuals with type 2 diabetes, in addition to comparing its treatment effects with those observed in non‐Latino/Hispanic individuals. Analyses were performed on patient‐level data from a subset of individuals self‐defined as Latino/Hispanic from four phase III studies, the LEAD‐3, LEAD‐4, LEAD‐6 and 1860‐LIRA‐DPP‐4 trials. Endpoints included change in glycated haemoglobin (HbA1c) and body weight from baseline. In Latino/Hispanic patients (n = 505; 323 treated with liraglutide) after 26 weeks, mean HbA1c reductions were significantly greater with both liraglutide 1.2 and 1.8 mg versus comparator or placebo in the LEAD‐3 and LEAD‐4 studies, and with 1.8 mg liraglutide in the 1860‐LIRA‐DPP‐4 trial. In LEAD‐3 both doses led to significant differences in body weight change among Latino/Hispanic patients versus the comparator. With 1.8 mg liraglutide, difference in weight change was significant only in the 1860‐LIRA‐DPP‐4 trial versus sitagliptin. For both endpoints Latino/Hispanic and non‐Latino/Hispanic patients responded to liraglutide similarly. In summary, liraglutide is efficacious for treatment of type 2 diabetes in Latino/Hispanic patients, with a similar efficacy to that seen in non‐Latino/Hispanic patients.     

利拉鲁肽对 2 型糖尿病阿尔茨海默病样三重转基因小鼠学习记忆的影响

目的 研究 2 型糖尿病 （T2DM） 对阿尔茨海默病 （AD） 样 APP/PS1/Tau 三重转基因 （3×Tg） 小鼠学习记忆能力的影响和利拉鲁肽 （LIR） 对此模型神经保护作用的相关机制。方法 将 1 月龄 C57BL/6 小鼠设为正常对照 （WT）组, 1 月龄 3×Tg 小鼠分为对照（Tg）组、 单纯利拉鲁肽（Tg+LIR）组、 Tg+T2DM 组、 T2DM+利拉鲁肽（Tg+T2DM+LIR）组。T2DM 造模方法为喂 2 个月高脂高糖饲料, 然后腹腔注射链脲佐菌素（STZ）, 空腹血糖大于 7 mmol/L 为造模成功, 腹腔注射 LIR 治疗 2 个月。5 月龄时测体质量、 空腹血糖。Morris 水迷宫检测空间学习记忆能力, Western blotting 检测 Tau、 神经丝 （NFs） 和胰岛素受体底物 （IRS） 磷酸化水平。ELISA 检测转入的人 APP 基因表达的人β淀粉样蛋白（Aβ） 42, 检测 LIR 对 Aβ的影响。结果 与 Tg 组比较, Tg+T2DM 组小鼠质量、 空腹血糖、 逃避潜伏期、 pT231、pT181、 SMI31、 Aβ42 增加, 穿越隐匿平台次数及 pIRS 减少。LIR 能减轻高脂高糖饮食及 T2DM 造成的体质量和血糖的增加, 能缓解 T2DM 对 3×Tg 小鼠空间学习记忆能力的损伤, 改善 T2DM 对 3×Tg 小鼠 Tau、 NFs 及 IRS 蛋白磷酸化的影响, 减少 3×Tg 小鼠的 Aβ沉积。结论 T2DM 会加重 3×Tg 小鼠的 AD样症状, 而 LIR 对其有保护作用。