Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA.
Curr Med Res Opin. 2012 Aug;28(8):1281-7. doi: 10.1185/03007995.2012.703134. Epub 2012 Jul 6.
In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA(1c) value.
Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA(1c) value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects.
Over the full range of HbA(1c) levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005).
The actual time between the HbA(1c) measurement and the hypoglycemic event was variable and not controlled for in the analysis.
In pre-specified analyses adjusting for the most recently measured HbA(1c) value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.
在之前发表的一项研究中，在接受二甲双胍治疗的 2 型糖尿病（T2DM）患者中，加用西格列汀或格列吡嗪治疗，52 周后 HbA（1c）均有相似程度的改善（两组均为-0.7%）。与格列吡嗪（584 例患者中 32%）相比，西格列汀（588 例患者中 5%）发生症状性低血糖的患者显著减少。血糖疗效和患者特征可能影响低血糖事件的发生。本分析通过校正最近测量的 HbA（1c）值，评估了西格列汀或格列吡嗪发生低血糖的风险。
本分析的数据来自上述 52 周、随机、双盲、阳性对照研究。主要终点为确诊低血糖（即症状性低血糖，同时伴有指尖血糖≤70mg/dL[3.9mmol/L]）；次要终点为严重低血糖（需要医疗或非医疗协助，或出现神经低血糖症状）。采用包含治疗、最近测量的 HbA（1c）值、时间（即随机化后天数）、性别和年龄（<65 岁或≥65 岁）的互补对数-log 回归随机效应模型，评估校正后的个体治疗效果。
在整个 HbA（1c）水平和随访时间范围内，与格列吡嗪相比，西格列汀发生确诊低血糖事件的风险较低（31 例 vs. 448 例；校正后的危害比[HR]为 0.05[95%CI：0.03，0.09]，p<0.001）。与格列吡嗪相比，西格列汀在年轻（HR 为 0.06[95%CI：0.03，0.12]，p<0.001）和年长（HR 为 0.02[0.01，0.08]，p<0.001）患者中发生低血糖的风险也较低。严重低血糖事件（2 例 vs. 22 例）的风险也较低（HR 为 0.08[95%CI：0.01，0.47]；p=0.005）。
HbA（1c）测量值与低血糖事件之间的实际时间不定，且在分析中未加以控制。
在根据最近测量的 HbA（1c）值进行的预先指定分析中，与加用二甲双胍治疗的患者加用格列吡嗪相比，西格列汀治疗可显著降低确诊低血糖的风险。在接受西格列汀治疗的年轻和年长患者中，确诊低血糖的风险非常低。
