Laboratory of Cardiovascular Prevention, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Centro Cardiologico Monzino IRCCS, Milan, Italy.
Diabetes Obes Metab. 2021 Jul;23(7):1484-1495. doi: 10.1111/dom.14361. Epub 2021 Mar 15.
To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy.
An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks.
After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency.
Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.
在意大利伦巴第和普利亚地区的大型未选择人群中，比较胰高血糖素样肽-1 受体激动剂（GLP-1RA）和钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂与其他抗高血糖药物（AHAs）在疗效和安全性方面的差异。
对 2010 年至 2018 年首次使用 GLP-1RA、SGLT2 抑制剂或其他 AHA 的患者进行了一项观察性队列研究。采用条件 Cox 模型在倾向评分匹配人群中评估死亡和心血管（CV）事件。计算了每个地区和汇总风险的调整后的危险比（HR）及其 95%置信区间（CI）。
在倾向评分匹配后，伦巴第队列包括 18716 名和 11683 名患者，普利亚队列分别包括 GLP-1RA 和 SGLT2 抑制剂组的 9772 名和 6046 名患者。GLP-1RA 的使用与死亡率降低相关（HR 0.61，CI 0.56-0.65，伦巴第；HR 0.63，CI 0.55-0.71，普利亚）、脑血管疾病和缺血性中风（HR 0.70，CI 0.63-0.79；HR 0.72，CI 0.60-0.87，伦巴第）、外周血管疾病（HR 0.72，CI 0.64-0.82，伦巴第；HR 0.80，CI 0.67-0.98，普利亚）和下肢并发症（HR 0.67，CI 0.56-0.81，伦巴第；HR 0.69，CI 0.51-0.93，普利亚）。与其他 AHAs 相比，SGLT2 抑制剂的使用降低了死亡风险（HR 0.47，CI 0.40-0.54，伦巴第；HR 0.43，CI 0.32-0.57，普利亚）、脑血管疾病（HR 0.75，CI 0.61-0.91，伦巴第；HR 0.72，CI 0.54-0.96，普利亚）和心力衰竭（HR 0.56，CI 0.46-0.70，伦巴第；HR 0.57，CI 0.42-0.77，普利亚）。在汇总队列中，GLP-1RA 也观察到心力衰竭的降低（HR 0.89，95%CI 0.82-0.97）。严重不良事件的发生率相当低。
我们从真实世界实践中获得的发现一致证实了 GLP-1RA 和 SGLT2 抑制剂在这两个地区对死亡和心血管结局的有益影响。因此，这些药物类别应优先考虑在广泛的 2 型糖尿病患者中使用，而不仅仅是在患有心血管疾病的患者中使用。
