OBJECTIVE The cardiovascular safety of saxagliptin, a dipeptidyl-peptidase 4 inhibitor, compared with other antihyperglycemic treatments is not well understood. We prospectively examined the association between saxagliptin use and acute myocardial infarction (AMI).

RESEARCH DESIGN AND METHODS We identified patients aged ≥18 years, starting from the approval date of saxagliptin in 2009 and continuing through August 2014, using data from 18 Mini-Sentinel data partners. We conducted seven sequential assessments comparing saxagliptin separately with sitagliptin, pioglitazone, second-generation sulfonylureas, and long-acting insulin, using disease risk score (DRS) stratification and propensity score (PS) matching to adjust for potential confounders. Sequential testing kept the overall chance of a false-positive signal below 0.05 (one-sided) for each pairwise comparison.

RESULTS We identified 82,264 saxagliptin users and more than 1.5 times as many users of each comparator. At the end of surveillance, the DRS-stratified hazard ratios (HRs) (95% CI) were 1.08 (0.90–1.28) in the comparison with sitagliptin, 1.11 (0.87–1.42) with pioglitazone, 0.79 (0.64–0.98) with sulfonylureas, and 0.57 (0.46–0.70) with long-acting insulin. The corresponding PS-matched HRs were similar. Only one interim analysis of 168 analyses met criteria for a safety signal: the PS-matched saxagliptin-pioglitazone comparison from the fifth sequential analysis, which yielded an HR of 1.63 (1.12–2.37). This association diminished in subsequent analyses.

CONCLUSIONS We did not find a higher AMI risk in saxagliptin users compared with users of other selected antihyperglycemic agents during the first 5 years after U.S. Food and Drug Administration approval of the drug.

目的与其他降糖药相比，沙格列汀（一种二肽基肽酶4抑制剂）在心血管方面的安全性尚不清楚。我们前瞻性地检查了沙格列汀的使用与急性心肌梗死（AMI）之间的关联。

研究设计和方法我们使用18个Mini-Sentinel数据合作伙伴的数据，从2009年沙格列汀的批准日期开始一直持续到2014年8月，确定年龄≥18岁的患者。我们进行了七项连续评估，分别使用沙格列汀，西格列汀，吡格列酮，第二代磺酰脲类和长效胰岛素进行比较，并使用疾病风险评分（DRS）分层和倾向评分（PS）进行匹配，以调整潜在的混杂因素。对于每个成对比较，顺序测试使假阳性信号的总体机会保持在0.05（单侧）以下。

结果我们确定了82,264名沙格列汀使用者，并且是每个比较者使用者的1.5倍以上。在监测结束时，与西他列汀相比，DRS分层风险比（HRs）（95％CI）为1.08（0.90–1.28），吡格列酮为1.11（0.87–1.42），磺酰脲类为0.79（0.64–0.98） ，长效胰岛素为0.57（0.46-0.70）。相应的PS匹配的HR相似。168项分析中仅有一项中期分析符合安全信号标准：第五次连续分析中PS匹配的沙格列汀-吡格列酮比较得出的HR为1.63（1.12-2.37）。这种联系在随后的分析中减弱了。

结论在美国食品和药物管理局批准该药物后的头5年内，与其他选定的降糖药使用者相比，沙格列汀使用者的AMI风险没有更高。