Patel Shrita, Hickman Anne, Frederich Robert, Johnson Susan, Huyck Susan, Mancuso James P, Gantz Ira, Terra Steven G
Merck & Co., Inc., Kenilworth, NJ, USA.
Pfizer Inc., Groton, CT, USA.
Diabetes Ther. 2020 Jun;11(6):1347-1367. doi: 10.1007/s13300-020-00803-3. Epub 2020 May 5.
The sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin is approved for the treatment of adults with type 2 diabetes mellitus (T2DM). This analysis was conducted on safety data pooled from phase 3 studies using ertugliflozin 5 mg or 15 mg versus placebo or an active comparator.
The placebo pool (n = 1544) comprised data from three similarly designed 26-week placebo-controlled studies. The broad pool (n = 4849) comprised these three placebo-controlled studies plus four placebo- or active-controlled studies with treatment durations of up to 104 weeks.
In the placebo pool, there were no notable differences across groups in the incidence of adverse events (AEs), serious AEs, or AEs resulting in discontinuation from study medication, while associations were observed with genital mycotic infection in both females (3.0%, 9.1%, and 12.2% in the placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg groups, respectively) and males (0.4%, 3.7%, 4.2%), thirst (0.2%, 1.3%, 1.0%), and increased urination (1.0%, 2.7%, 2.4%). In the broad pool, volume depletion was increased with ertugliflozin in patients with estimated glomerular filtration rate < 60 ml/min/1.73 m, aged ≥ 65 years, or who were taking diuretics. Ertugliflozin was not associated with increased urinary tract infection, fracture, hypoglycemia, pancreatitis, renal or hepatic injury, hypersensitivity, malignancy, or venous thromboembolism. Small numbers of patients were reported with lower limb amputation [0.1% (non-ertugliflozin group), 0.2% (ertugliflozin 5 mg), 0.5% (ertugliflozin 15 mg)]. There were three cases of ketoacidosis (all ertugliflozin 15 mg) and no cases of Fournier's gangrene.
This pooled analysis showed that ertugliflozin was generally well tolerated in a large population of patients with T2DM with and without moderate renal impairment who were taking a range of background diabetes medications including insulin and insulin secretagogs, with results that are generally consistent with those for other SGLT2 inhibitors.
Clinicaltrials.gov indentifier, NCT02033889, NCT01958671, NCT02036515, NCT01986855, NCT02099110, NCT02226003, NCT01999218.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂依鲁格列净已被批准用于治疗成年2型糖尿病（T2DM）患者。本分析基于3期研究汇总的安全性数据进行，这些研究比较了5毫克或15毫克依鲁格列净与安慰剂或活性对照药。
安慰剂组（n = 1544）的数据来自三项设计相似的为期26周的安慰剂对照研究。广泛组（n = 4849）的数据包括这三项安慰剂对照研究以及四项治疗时长最长达104周的安慰剂或活性对照研究。
在安慰剂组中，各治疗组在不良事件（AE）、严重AE或导致停用研究药物的AE发生率方面无显著差异，但观察到女性（安慰剂组、依鲁格列净5毫克组和依鲁格列净15毫克组的发生率分别为3.0%、9.1%和12.2%）和男性（0.4%、3.7%、4.2%）的生殖器真菌感染、口渴（0.2%、1.3%和1.0%）以及尿量增加（1.0%、2.7%和2.4%）之间存在关联。在广泛组中，估计肾小球滤过率<60 ml/min/1.73 m²、年龄≥65岁或正在服用利尿剂的患者使用依鲁格列净后血容量减少增加。依鲁格列净与尿路感染、骨折、低血糖、胰腺炎、肾或肝损伤、超敏反应、恶性肿瘤或静脉血栓栓塞的增加无关。报告有少数患者发生下肢截肢[0.1%（非依鲁格列净组）、0.2%（依鲁格列净5毫克组）、0.5%（依鲁格列净15毫克组）]。有3例酮症酸中毒（均为依鲁格列净15毫克组），无福尼尔坏疽病例。
这项汇总分析表明，在大量T2DM患者中，无论有无中度肾功能损害，且正在服用包括胰岛素和胰岛素促泌剂在内的多种背景糖尿病药物，依鲁格列净总体耐受性良好，结果与其他SGLT2抑制剂的结果基本一致。
Clinicaltrials.gov标识符，NCT02033889、NCT01958671、NCT02036515、NCT01986855、NCT02099110、NCT02226003、NCT01999218。
