Iqbal Nayyar, Allen Elsie, Öhman Peter
Bristol-Myers Squibb, Princeton, NJ, USA.
AstraZeneca, Wilmington, DE, USA.
Clin Interv Aging. 2014 Sep 4;9:1479-87. doi: 10.2147/CIA.S68193. eCollection 2014.
Treatment decisions for older patients with type 2 diabetes mellitus must balance glycemic control and adverse event risk. The objective of this study was to evaluate the long-term safety and tolerability of saxagliptin 5 mg as add-on therapy to common antihyperglycemic drugs in patients aged ≥ 65 years and <65 years.
Pooled adverse event data from three placebo-controlled trials of 76-206 weeks' duration in older (≥ 65 years) and younger (<65 years) patients receiving saxagliptin 5 mg or matching placebo added to metformin, glyburide, or a thiazolidinedione were analyzed. Measurements were calculated from day of first dose to specified event or last dose and included time at risk for adverse events, treatment-related adverse events, serious adverse events, adverse events leading to discontinuation, and events of special interest. Weighted incidence rates (number of events/total time) and incidence rate ratios (saxagliptin/placebo) with 95% confidence intervals were calculated (Mantel-Haenszel test).
A total of 205 older (mean age 69 years; saxagliptin, n=99; placebo, n=106) and 1,055 younger (mean age 52 years; saxagliptin, n=531; placebo, n=524) patients were assessed. Regardless of age category, the adverse event incidence rates were generally similar between treatments, with confidence intervals for incidence rate ratios bridging 1. Treatment-related adverse events occurred in 36 older patients receiving saxagliptin versus 32 receiving placebo (incidence rate 34.1 versus 27.1 per 100 person-years) and in 150 younger patients in both treatment groups (incidence rate 24.0 versus 27.8 per 100 person-years). With saxagliptin versus placebo, serious adverse events occurred in eight versus 14 older (incidence rate 5.7 versus 9.9 per 100 person-years) and 49 versus 44 younger patients (incidence rate 6.5 versus 6.6 per 100 person-years). There were two deaths (one patient ≥ 65 years) with saxagliptin and six (none aged ≥ 65 years) with placebo. Older patients rarely experienced symptomatic confirmed hypoglycemia (fingerstick glucose ≤ 50 mg/dL; saxagliptin, n=1; placebo, n=2).
Saxagliptin add-on therapy was generally well tolerated in older patients aged ≥ 65 years with type 2 diabetes mellitus, with a long-term safety profile similar to that of placebo.
老年2型糖尿病患者的治疗决策必须在血糖控制和不良事件风险之间取得平衡。本研究的目的是评估5mg沙格列汀作为≥65岁和<65岁患者常用降糖药物的附加疗法的长期安全性和耐受性。
分析了三项安慰剂对照试验的汇总不良事件数据，这些试验持续76 - 206周，纳入了接受5mg沙格列汀或匹配安慰剂加二甲双胍、格列本脲或噻唑烷二酮的老年（≥65岁）和年轻（<65岁）患者。测量从首次给药日到特定事件或末次给药计算，包括不良事件的风险时间、治疗相关不良事件、严重不良事件、导致停药的不良事件以及特殊关注事件。计算加权发病率（事件数/总时间）和发病率比（沙格列汀/安慰剂）及其95%置信区间（Mantel-Haenszel检验）。
共评估了205例老年患者（平均年龄69岁；沙格列汀组，n = 99；安慰剂组，n = 106）和1055例年轻患者（平均年龄52岁；沙格列汀组，n = 531；安慰剂组，n = 524）。无论年龄组如何，各治疗组之间的不良事件发生率总体相似，发病率比的置信区间跨越1。接受沙格列汀的36例老年患者与接受安慰剂的32例老年患者发生治疗相关不良事件（发病率分别为每100人年34.1例和27.1例），两个治疗组的150例年轻患者也发生了治疗相关不良事件（发病率分别为每100人年24.0例和27.8例）。与安慰剂相比，沙格列汀组有8例老年患者和49例年轻患者发生严重不良事件，安慰剂组分别为14例老年患者和44例年轻患者（发病率分别为每100人年5.7例和9.9例，以及每100人年6.5例和6.6例）。沙格列汀组有2例死亡（1例≥65岁患者），安慰剂组有6例死亡（无≥65岁患者）。老年患者很少发生症状性确诊低血糖（指尖血糖≤50mg/dL；沙格列汀组，n = 1；安慰剂组，n = 2）。
对于≥65岁的老年2型糖尿病患者，沙格列汀附加疗法总体耐受性良好，长期安全性与安慰剂相似。
