Effectiveness and safety of combining SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 2 diabetes: a systematic review and meta-analysis of cohort studies.

However, the effect of combining these drugs remains uncertain.

然而，联合使用这些药物的效果仍不确定。

This systematic reviewaimed to evaluate the potential effectiveness and safety of combination therapy compared with monotherapy in individuals with type 2 diabetes.

本系统评价旨在评估与单一疗法相比，联合疗法在2型糖尿病患者中的潜在有效性和安全性。

method

We systematically searched PubMed and Embase from inception to 1 May 2025 for cohort studies comparing the effect of combination therapy with SGLT2 inhibitor or GLP-1 RA monotherapy on (cardiovascular) mortality and cardiovascular or kidney endpoints in individuals with type 2 diabetes.

我们从建库开始至2025年5月1日，系统性地在PubMed和Embase中检索了比较联合疗法与SGLT2抑制剂或GLP-1 RA单一疗法在2型糖尿病患者中对（心血管）死亡率以及心血管或肾脏终点事件影响的队列研究。

Studies enrolling individuals with type 1 diabetes or a maximum follow-up of less than 1 year were excluded.

排除了招募1型糖尿病患者或最大随访期少于1年的研究。

The primary outcome was a composite of major adverse cardiovascular events (MACE).

主要结果是重大不良心血管事件（MACE）的复合指标。

Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalisation for heart failure, a kidney composite endpoint and serious adverse events.

次要结果包括全因死亡率、心血管死亡率、因心力衰竭住院、肾脏复合终点事件和严重不良事件。

Risk of bias was assessed with ROBINS-I.

使用ROBINS-I评估偏倚风险。

Risk ratios (RRs) and 95% CIs were pooled in random effects meta-analyses.

通过随机效应的荟萃分析，合并了风险比（RRs）和95%置信区间（CIs）。

Certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE).

使用推荐、评估、发展和评估的证据质量（GRADE）方法评估了证据的确定性。

Results

We included 18 cohort studies (1,164,774 participants).

我们纳入了18项队列研究（共1,164,774名参与者）。

In cohort studies, combination therapy was associated with a lower risk of MACE (RR 0.56 [95% CI 0.43, 0.71]; low certainty of evidence) and the kidney composite endpoint (RR 0.48 [95% CI 0.32, 0.73]; very low certainty of evidence) relative to SGLT2 inhibitor or GLP-1 RA monotherapy.

在队列研究中，联合治疗与单一使用SGLT2抑制剂或GLP-1 RA相比，主要心血管不良事件（MACE）的风险较低（相对风险0.56 [95%置信区间0.43, 0.71]；证据确定性低）以及肾脏复合终点事件的风险较低（相对风险0.48 [95%置信区间0.32, 0.73]；证据确定性非常低）。

Combination therapy was also associated with a lower risk of all-cause mortality (RR 0.50 [95% CI 0.40, 0.63]; low certainty of evidence), cardiovascular mortality (RR 0.26 [95% CI 0.16, 0.43]; low certainty of evidence) and hospitalisation for heart failure (RR 0.67 [95% CI 0.64, 0.71]; moderate certainty of evidence).

联合治疗还与较低的全因死亡风险相关（RR 0.50 [95% CI 0.40, 0.63]；证据确定性低），心血管死亡风险（RR 0.26 [95% CI 0.16, 0.43]；证据确定性低）以及因心力衰竭住院风险（RR 0.67 [95% CI 0.64, 0.71]；证据确定性中等）。

Although safety data could not be pooled due to lack of events, no differences were observed in the risk of severe hypoglycaemia, diabetic ketoacidosis, genitourinary infections and gastrointestinal side effects.

尽管由于缺乏事件而无法汇总安全性数据，但在严重低血糖、糖尿病酮症酸中毒、泌尿生殖系统感染和胃肠道副作用的风险方面未观察到差异。

No data were reported on the risk of serious adverse events or major adverse limb events.

没有报告关于严重不良事件或主要下肢不良事件风险的数据。

conclusions/interpretation

Observational studies suggest that combining an SGLT2 inhibitor and a GLP-1 RA in type 2 diabetes may lower the risk of MACE, all-cause and cardiovascular mortality, hospitalisation for heart failure and kidney composite endpoints compared with monotherapy with either drug.

观察性研究表明，在2型糖尿病中，联合使用SGLT2抑制剂和GLP-1 RA可能比单独使用任一药物更能降低MACE、全因和心血管死亡率、心力衰竭住院和肾脏复合终点的风险。

Of course, residual confounding cannot be overcome but results support the need for future randomised trials of combined vs monotherapy.

当然，无法克服残余混杂因素，但结果支持未来进行联合治疗与单一治疗比较的随机试验的需要。

registration

PROSPERO registration no.

PROSPERO注册号：

CRD42024532383.

CRD42024532383。