Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA1c Levels.
Comparing Effectiveness and Safety of SGLT2 Inhibitors vs DPP-4 Inhibitors in Patients With Type 2 Diabetes and Varying Baseline HbA1c Levels.
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DOI：
10.1001/jamainternmed.2022.6664
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发表时间：
2023-03-01
影响因子：
39
通讯作者：
Patorno, Elisabetta
中科院分区：
文献类型：
--
作者：
D'Andrea, Elvira;Wexler, Deborah J.;Kim, Seoyoung C.;Paik, Julie M.;Alt, Ethan;Patorno, Elisabetta
钠-葡萄糖协同转运蛋白2抑制剂（SGLT 2 i）与二肽基肽酶4抑制剂（DPP-4 i）在总体和不同基线血红蛋白A1 c（HbA 1c）水平的2型糖尿病（T2 D）患者中的有效性和安全性是否存在差异？在这项大型新使用者比较有效性和安全性研究中，纳入了87274例倾向评分匹配的T2 D成人患者，与DPP-4 i治疗启动者相比，SGLT 2 i治疗启动者的主要心血管事件、心力衰竭和急性肾损伤风险降低，生殖器感染和糖尿病酮症酸中毒风险增加，无论基线HbA 1c水平如何。尽管担心在较高HbA 1c水平下使用SGLT 2 i会导致过度风险，但本研究的结果表明，无论血糖控制如何，T2 D患者均可从使用SGLT 2 i中获益，与DPP-4 i相比，具有预期的不良反应特征，在HbA 1c水平升高的患者中没有额外的不良反应风险。钠-葡萄糖协同转运蛋白2抑制剂（SGLT 2 i）治疗与心血管获益和少数不良事件相关;然而，比较有效性和安全性特征是否随基线血红蛋白A1 c（HbA 1c）水平的差异而变化尚不清楚。比较SGLT 2 i与二肽基肽酶4抑制剂（DPP-4 i）治疗2型糖尿病（T2 D）成人患者的心血管有效性和安全性（1）总体和（2）不同基线HbA 1c水平。在144614名开始接受SGLT 2 i或DPP-4 i治疗的商业保险成人中进行了一项新使用者疗效和安全性比较研究，这些成人在基线时记录了T2 D诊断，并在治疗开始前3个月内记录了至少1次HbA 1c实验室检查结果。干预包括开始SGLT 2 i或DPP-4 i治疗。主要结局为心肌梗死、卒中或全因死亡（改良主要不良心血管事件[MACE]）和因心力衰竭住院（HHF）的复合终点。安全性结局为低血容量、骨折、福尔斯、生殖器感染、糖尿病酮症酸中毒（DKA）、急性肾损伤（阿基）和下肢截肢。控制128个协变量，估计每1000人-年的发病率（IR）、风险比（HR）和率差（RD）及其95% CI。144614名合资格成年人（平均[SD]年龄，62 [12.4]岁; 54%为男性受试者）开始接受SGLT 2 i治疗的T2 D患者（n = 60 523）或DPP-4 i（n = 84 091）; 44 099例HbA 1c基线值小于7.5%，52 986例介于7.5%和9%之间，47 529例大于9%。总体而言，87274例合格患者的倾向评分为1：1匹配：24052例HbA 1c低于7.5%; 32290例HbA 1c介于7.5%和9%之间; 30932例HbA 1c大于9%（将总血红蛋白百分比转换为总血红蛋白比例，乘以0.01）。开始SGLT 2 i与DPP-4 i相比与改良MACE风险降低相关（每1000人年的IR分别为17.13 vs 20.18; HR，0.85; 95% CI，0.75-0.95; RD，-3.02; 95% CI，−5.23至-0.80）和HHF（每1000人年的IR分别为3.68 vs 8.08; HR为0.46; 95% CI为0.35 - 0.57; RD为-4.37;平均随访8个月，95% CI，−5.62至−3.12），没有证据表明HbA 1c水平之间存在治疗效应异质性。与DPP-4 i相比，SGLT 2 i治疗显示生殖器感染和DKA风险增加，阿基风险降低。不同HbA 1c水平的结果一致，但与SGLT 2 i相关的生殖器感染风险更显著，HbA 1c水平为7.5%-9%（IR/1000人-年分别为68.5 vs 22.8; HR，3.10; 95% CI，2.68-3.58; RD，46.22; 95% CI，40.54-51.90）。在这项在T2 D成人患者中进行的有效性和安全性比较研究中，SGLT 2 i与DPP-4 i治疗启动者相比，改良MACE和HHF的风险降低，生殖器感染和DKA的风险增加，阿基的风险降低，与基线HbA 1c无关。这项有效性比较研究评价了SGLT 2抑制剂与DPP-4抑制剂在总体和不同基线HbA 1c水平的2型糖尿病成人患者中的心血管有效性和安全性。
Does the effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i) differ from that of dipeptidyl peptidase 4 inhibitors (DPP-4i) in patients with type 2 diabetes (T2D) overall and at varying baseline hemoglobin A1c (HbA1c) levels? In this large new-user comparative effectiveness and safety research study including 87 274 propensity-scored matched adults with T2D, SGLT2i treatment initiators had a reduced risk of major cardiovascular events, heart failure, and acute kidney injury and an increased risk of genital infections and diabetic ketoacidosis compared with DPP-4i treatment initiators, regardless of their baseline HbA1c level. Despite concern that use of SGLT2i at higher HbA1c levels would cause excess risk, the findings of this study suggest that patients with T2D can benefit from the use of SGLT2i regardless of glycemic control, with the expected adverse effect profile when compared with DPP-4i, with no additional risk of adverse effects in patients with elevated HbA1c levels. Sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy has been associated with cardiovascular benefits and a few adverse events; however, whether the comparative effectiveness and safety profiles vary with differences in baseline hemoglobin A1c (HbA1c) levels is unknown. To compare cardiovascular effectiveness and safety of treatment with SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP-4i) in adults with type 2 diabetes (T2D) (1) overall and (2) at varying baseline HbA1c levels. A new-user comparative effectiveness and safety research study was conducted among 144 614 commercially insured adults, initiating treatment with SGLT2i or DPP-4i and with a recorded T2D diagnosis at baseline and at least 1 HbA1c laboratory result recorded within 3 months before treatment initiation. The intervention consisted of the initiation of treatment with SGLT2i or DPP-4i. Primary outcomes were a composite of myocardial infarction, stroke, or all-cause death (modified major adverse cardiovascular events [MACE]) and hospitalization for heart failure (HHF). Safety outcomes were hypovolemia, fractures, falls, genital infections, diabetic ketoacidosis (DKA), acute kidney injury (AKI), and lower-limb amputation. Incidence rate (IR) per 1000 person-years, hazard ratios (HR) and rate differences (RD) with their 95% CIs were estimated controlling for 128 covariates. A total of 144 614 eligible adults (mean [SD] age, 62 [12.4] years; 54% male participants) with T2D initiating treatment with a SGLT2i (n = 60 523) or a DPP-4i (n = 84 091) were identified; 44 099 had an HbA1c baseline value of less than 7.5%, 52 986 between 7.5% and 9%, and 47 529 greater than 9%. Overall, 87 274 eligible patients were 1:1 propensity score–matched: 24 052 with HbA1c less than 7.5%; 32 290 with HbA1c between 7.5% and 9%; and 30 932 with HbA1c greater than 9% (to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01). The initiation of SGLT2i vs DPP-4i was associated with a reduction in the risk of modified MACE (IR per 1000 person-years 17.13 vs 20.18, respectively; HR, 0.85; 95% CI, 0.75-0.95; RD, −3.02; 95% CI, −5.23 to –0.80) and HHF (IR per 1000 person-years 3.68 vs 8.08, respectively; HR, 0.46; 95% CI, 0.35 to 0.57; RD −4.37; 95% CI, −5.62 to −3.12) over a mean follow-up of 8 months, with no evidence of treatment effect heterogeneity across the HbA1c levels. Treatment with SGLT2i showed an increased risk of genital infections and DKA and a reduced AKI risk compared with DPP-4i. Findings were consistent by HbA1c levels, except for a more pronounced risk of genital infections associated with SGLT2i for HbA1c levels of 7.5% to 9% (IR per 1000 person-years 68.5 vs 22.8, respectively; HR, 3.10; 95% CI, 2.68-3.58; RD, 46.22; 95% CI, 40.54-51.90). In this comparative effectiveness and safety research study among adults with T2D, SGLT2i vs DPP-4i treatment initiators had a reduced risk of modified MACE and HHF, an increased risk of genital infections and DKA, and a lower risk of AKI, regardless of baseline HbA1c. This comparative effectiveness study evaluates cardiovascular effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in adults with type 2 diabetes overall and at varying baseline HbA1c levels.
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影响因子：
8.2
作者：
Lin, Donna Shu-Han;Lee, Jen-Kuang;Chen, Wen-Jone
通讯作者：
Chen, Wen-Jone
影响因子：
4
作者：
Bobo WV;Cooper WO;Epstein RA Jr;Arbogast PG;Mounsey J;Ray WA
通讯作者：
Ray WA
影响因子：
7.2
作者：
Newton, KM;Wagner, EH;Davis, C
通讯作者：
Davis, C
影响因子：
24
作者：
Berg, David D.;Jhund, Pardeep S.;Sabatine, Marc S.
通讯作者：
Sabatine, Marc S.
DOI：
10.1136/bmj.m3342
发表时间：
2020-09-23
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Filion KB;Lix LM;Yu OH;Dell'Aniello S;Douros A;Shah BR;St-Jean A;Fisher A;Tremblay E;Bugden SC;Alessi-Severini S;Ronksley PE;Hu N;Dormuth CR;Ernst P;Suissa S;Canadian Network for Observational Drug Effect Studies (CNODES) Investigators
通讯作者：
Canadian Network for Observational Drug Effect Studies (CNODES) Investigators