Klein Klara R, Abrahamsen Trine J, Kahkoska Anna R, Alexander G Caleb, Chute Christopher G, Haendel Melissa, Hong Stephanie S, Mehta Hemalkumar, Moffitt Richard, Stürmer Til, Kvist Kajsa, Buse John B
Division of Endocrinology and Metabolism, Department of Medicine, University of North Carolina School of Medicine, Campus Box #7172, 8072 Burnett Womack, 160 Dental Circle, Chapel Hill, NC, 27599, USA.
Novo Nordisk A/S, Søborg, Denmark.
Diabetes Ther. 2024 May;15(5):1169-1186. doi: 10.1007/s13300-024-01562-1. Epub 2024 Mar 27.
People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24 months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14 days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE).
Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56-0.72) and SGLT-2i (OR 0.62, 95% CI 0.57-0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81-1.05 and OR 0.88, 95% CI 0.76-1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone.
Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article.
2型糖尿病患者感染新型冠状病毒肺炎（COVID-19）后出现严重后果的风险更高，包括住院、入住重症监护病房和死亡。本研究旨在探讨病前使用胰高血糖素样肽-1受体激动剂（GLP-1RA）单药治疗、钠-葡萄糖协同转运蛋白-2抑制剂（SGLT-2i）单药治疗以及GLP-1RA/SGLT-2i联合治疗对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染患者结局严重程度的影响。
利用截至2022年9月的国家COVID队列协作组织的观察性数据，我们比较了78806例在SARS-CoV-2聚合酶链反应（PCR）检测呈阳性后24个月内开具GLP-1RA和SGLT-2i处方的患者与开具二肽基肽酶4抑制剂（DPP-4i）处方的患者的结局。我们还比较了GLP-1RA/SGLT-2i联合治疗与GLP-1RA和SGLT-2i单药治疗。主要结局是自检测阳性日期起的60天死亡率。次要结局包括14天内的急诊室就诊、住院和机械通气。采用超级学习方法并考虑基线特征，通过目标最大似然估计（TMLE）估计的比值比（OR）对关联进行量化。
与使用DPP-4i相比，使用GLP-1RA（OR 0.64，95%置信区间[CI] 0.56 - 0.72）和SGLT-2i（OR 0.62，95% CI 0.57 - 0.68）与60天死亡率的较低比值相关。此外，使用GLP-1RA和SGLT-2i时急诊室就诊和住院的OR也同样降低。与单独使用GLP-1RA或SGLT-2i相比，联合使用GLP-1RA/SGLT-2i时60天死亡率的比值相似（分别为OR 0.92，95% CI 0.81 - 1.05和OR 0.88，95% CI 0.76 - 1.01）。然而，与单独使用SGLT-2i相比，联合使用GLP-1RA/SGLT-2i时所有次要结局的OR均较低。
在SARS-CoV-2检测呈阳性的成年人中，与DPP-4i相比，病前使用GLP-1RA或SGLT-2i与较低的死亡几率相关。此外，与单独使用SGLT-2i相比，联合使用GLP-1RA和SGLT-2i与其他严重COVID-19结局的较低几率相关，包括急诊室就诊、住院和机械通气。本文提供图形摘要。
