Ludwig Maximilian University of Munich, Department of Internal Medicine, Munich, Germany.
Int J Clin Pract. 2013 Apr;67(4):307-16. doi: 10.1111/ijcp.12119.
To compare the long-term safety, tolerability and efficacy of saxagliptin vs. glipizide as add-on therapy to metformin.
Adults with glycated haemoglobin (HbA1c) > 6.5-10% (on stable metformin ≥ 1500 mg/day) were randomised to saxagliptin 5 mg/day (n = 428) or glipizide titrated from 5 to 20 mg/day (mean dose 15 mg/day; n = 430) for 52 weeks with a 52-week extension (NCT00575588). Assessment of the long-term safety, tolerability and efficacy of add-on saxagliptin vs. glipizide after 104 weeks was a tertiary objective of the initial 52-week study.
Saxagliptin was well tolerated during the 104-week period; 67.1% of patients receiving saxagliptin vs. 72.6% receiving glipizide had ≥ 1 adverse event (AE), and few patients (4.9% vs. 5.6%) discontinued owing to AEs. Fewer patients treated with saxagliptin experienced hypoglycaemia (3.5% vs. 38.4% with glipizide; difference, -34.9%, 95% CI, -39.8 to -30.0) or confirmed hypoglycaemia (0 vs. 9.1% with glipizide). Weight loss was observed with saxagliptin (-1.5 kg) vs. weight gain with glipizide (+1.3 kg; between-group difference, -2.8 kg, 95% CI, -3.32 kg to -2.20 kg). Change from baseline in HbA1c was -0.41 ± 0.04% with saxagliptin and -0.35 ± 0.04% with glipizide (between-group difference, -0.05%, 95% CI, -0.17 to 0.06%). A post hoc analysis showed that the proportion of patients with baseline HbA1c ≥ 7% who achieved HbA1c < 7% (observed data) at week 104 was 23.1% for saxagliptin + metformin and 22.7% for glipizide + metformin.
A lower risk of hypoglycaemia and reduced body weight were observed with saxagliptin vs. glipizide. No other clinically significant differences were observed between groups in safety profile. No significant between-group differences were observed for reductions in glycaemic parameters. After week 24, a smaller weekly rise in HbA1c was observed with saxagliptin vs. glipizide as add-on therapy to metformin.
比较沙格列汀与格列吡嗪作为二甲双胍的附加疗法的长期安全性、耐受性和疗效。
糖化血红蛋白（HbA1c）＞6.5-10%（稳定接受二甲双胍≥1500mg/天）的成年人被随机分配接受沙格列汀 5mg/天（n=428）或格列吡嗪起始剂量 5mg/天滴定至 20mg/天（平均剂量 15mg/天；n=430），疗程为 52 周，随后进行 52 周的扩展（NCT00575588）。在初始 52 周研究中，评估添加沙格列汀与格列吡嗪治疗 104 周后的长期安全性、耐受性和疗效是次要目标。
在 104 周期间，沙格列汀的耐受性良好；接受沙格列汀治疗的患者中有 67.1%发生了≥1 次不良事件（AE），而接受格列吡嗪治疗的患者有 72.6%发生了≥1 次不良事件（差异，-34.9%，95%CI，-39.8 至-30.0）；接受沙格列汀治疗的患者中仅有 4.9%因 AE 而停药，而接受格列吡嗪治疗的患者有 5.6%因 AE 而停药。接受沙格列汀治疗的患者发生低血糖（3.5%）和确诊低血糖（0%）的比例低于接受格列吡嗪治疗的患者（低血糖，38.4%；确诊低血糖，9.1%）。与格列吡嗪相比，沙格列汀导致体重减轻（-1.5kg），而格列吡嗪导致体重增加（+1.3kg；组间差异，-2.8kg，95%CI，-3.32kg 至-2.20kg）。与基线相比，沙格列汀治疗使 HbA1c 降低了 0.41±0.04%，格列吡嗪治疗使 HbA1c 降低了 0.35±0.04%（组间差异，-0.05%，95%CI，-0.17 至 0.06）。一项事后分析显示，在基线 HbA1c≥7%的患者中，沙格列汀+二甲双胍组有 23.1%的患者在第 104 周时达到了 HbA1c＜7%（观察数据），格列吡嗪+二甲双胍组有 22.7%的患者达到了这一目标。
与格列吡嗪相比，沙格列汀治疗导致低血糖和体重减轻的风险较低。两组的安全性特征无其他临床意义上的显著差异。两组在降低血糖参数方面无显著差异。与格列吡嗪作为附加疗法相比，沙格列汀治疗后每周 HbA1c 的升高幅度较小。
