Jones Nigel P, Curtis Paula S, Home Philip D
GlaxoSmithKline, 1-3 Iron Bridge Road, Stockley Park West, Uxbridge, UB11 1BT, UK,
Acta Diabetol. 2015 Jun;52(3):539-46. doi: 10.1007/s00592-014-0691-y. Epub 2014 Dec 19.
The RECORD study evaluated the effects of rosiglitazone on cardiovascular outcomes. A 4-year observational follow-up was added to the study to monitor the occurrence of cancer and bone fractures. We present the cancer and bone fracture data aggregated across the main study and its observational follow-up.
RECORD was a multicentre, open-label trial in people with type 2 diabetes on metformin or sulfonylurea monotherapy randomly assigned to addition of rosiglitazone (n = 2,220) or to a combination of metformin and sulfonylurea (n = 2,227). At the end of the main study, patients stopped study drug and were invited to enter the observational follow-up during which glucose-lowering treatment was selected by the patient's physician. Serious adverse events of cancer and serious and non-serious events of bone fracture were recorded. The study is registered with ClinicalTrials.gov, number NCT00379769.
Of the 4,447 patients comprising the intent-to-treat population, 2,546 entered the observational follow-up (1,288 rosiglitazone, 1,258 metformin/sulfonylurea) and added 9,336 patient-years experience to the main RECORD study, making an aggregate of 33,744 patient-years. Based on the totality of follow-up, malignancies were reported in 179 of 2,220 patients (8.1 %) in the group originally randomised to rosiglitazone and in 195 of 2,227 patients (8.8 %) in the group allocated metformin/sulfonylurea [relative risk, RR, 0.92 (95 % CI 0.76-1.12)]. More patients reported bone fractures in the rosiglitazone group (238, 10.7 %) than in the metformin/sulfonylurea control [151, 6.8 %; RR 1.58 (1.30-1.92)]. For women, the corresponding figures were rosiglitazone 156 (14.5 %), metformin/sulfonylurea 91 (8.5 %), RR 1.71 (1.34-2.18), and for men, the corresponding figures were rosiglitazone 82 (7.2 %), metformin/sulfonylurea 60 (5.2 %), RR 1.37 (0.99-1.90). Potentially high-morbidity fractures (hip, pelvis, femur, and spine) occurred in the same number of patients (31, 1.4 %) in the two treatment groups.
We conclude that data from a 4-year observational follow-up, combined with the main RECORD study data, do not suggest an increased risk of cancer in patients randomised to rosiglitazone combination use compared with those randomised to metformin/sulfonylurea. Consistent with the main study, rosiglitazone is associated with an increased risk of peripheral bone fracture in women, and probably in men, but the combined data do not suggest an increase in potentially high-morbidity (hip, pelvis, femur, and spine) fractures.
“RECORD研究”评估了罗格列酮对心血管结局的影响。该研究增加了4年的观察性随访，以监测癌症和骨折的发生情况。我们展示了在主要研究及其观察性随访中汇总的癌症和骨折数据。
“RECORD研究”是一项多中心、开放标签试验，纳入接受二甲双胍或磺脲类单药治疗的2型糖尿病患者，将其随机分配至加用罗格列酮组（n = 2220）或二甲双胍与磺脲类联合治疗组（n = 2227）。在主要研究结束时，患者停用研究药物，并受邀进入观察性随访阶段，在此期间降糖治疗由患者的医生选择。记录癌症的严重不良事件以及骨折的严重和非严重事件。该研究已在ClinicalTrials.gov注册，注册号为NCT00379769。
在构成意向性治疗人群的4447例患者中，2546例进入观察性随访（罗格列酮组1288例，二甲双胍/磺脲类组1258例），为“RECORD主要研究”增加了9336患者年的经验，总计33744患者年。基于全部随访情况，最初随机分配至罗格列酮组的2220例患者中有179例（8.1%）报告发生恶性肿瘤，分配至二甲双胍/磺脲类组的2227例患者中有195例（8.8%）报告发生恶性肿瘤[相对危险度（RR）为0.92（95%置信区间0.76 - 1.12）]。罗格列酮组报告骨折的患者（238例，10.7%）多于二甲双胍/磺脲类对照组[151例，6.8%；RR为1.58（1.30 - 1.92）]。对于女性，相应数据为罗格列酮组156例（14.5%），二甲双胍/磺脲类组91例（8.5%），RR为1.71（1.34 - 2.18）；对于男性，相应数据为罗格列酮组82例（7.2%），二甲双胍/磺脲类组60例（5.2%），RR为1.37（0.99 - 1.90）。两个治疗组中发生潜在高致残性骨折（髋部、骨盆、股骨和脊柱）的患者数量相同（31例，1.4%）。
我们得出结论，4年观察性随访数据与“RECORD主要研究”数据相结合，未提示随机接受罗格列酮联合治疗的患者比随机接受二甲双胍/磺脲类治疗的患者患癌风险增加。与主要研究一致，罗格列酮与女性外周骨折风险增加相关，男性可能也如此，但综合数据未提示潜在高致残性（髋部、骨盆、股骨和脊柱）骨折增加。
