Diabetes Care. 2018 Jan;41(1):39-48. doi: 10.2337/dc17-0476. Epub 2017 Nov 9.
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).
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.
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.
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.
二肽基肽酶 4 抑制剂沙格列汀的心血管安全性与其他降血糖治疗相比尚不清楚。我们前瞻性地研究了沙格列汀的使用与急性心肌梗死（AMI）之间的关系。
我们使用来自 18 个 Mini-Sentinel 数据合作伙伴的数据，从沙格列汀于 2009 年获得批准之日起，确定了年龄≥18 岁的患者，并持续至 2014 年 8 月。我们使用疾病风险评分（DRS）分层和倾向评分（PS）匹配，对每个配对比较分别将沙格列汀与西格列汀、吡格列酮、第二代磺酰脲类药物和长效胰岛素进行了七次连续评估，以调整潜在的混杂因素。连续测试使每个两两比较的假阳性信号的总体机会保持在 0.05（单侧）以下。
我们确定了 82264 名沙格列汀使用者和每个比较药物的使用者的 1.5 倍以上。在监测结束时，DRS 分层风险比（HR）（95%CI）分别为与西格列汀比较为 1.08（0.90-1.28），与吡格列酮比较为 1.11（0.87-1.42），与磺酰脲类药物比较为 0.79（0.64-0.98），与长效胰岛素比较为 0.57（0.46-0.70）。相应的 PS 匹配 HR 也相似。在 168 项分析中，只有一项中期分析符合安全性信号标准：第五次连续分析中 PS 匹配的沙格列汀-吡格列酮比较，其 HR 为 1.63（1.12-2.37）。这种关联在随后的分析中减弱了。
在沙格列汀获得美国食品和药物管理局批准后的前 5 年，与其他选定的降血糖药物相比，我们没有发现使用沙格列汀的患者 AMI 风险更高。
