Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
J Gen Intern Med. 2023 Jan;38(1):107-114. doi: 10.1007/s11606-022-07726-8. Epub 2022 Jul 13.
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) are increasingly recommended in type 2 diabetes. Hypoglycemia is a serious adverse effect of glucose-lowering agents. Real-world comparison of hypoglycemic risks among SGLT2i, GLP1RA, dipeptidyl peptidase-4 inhibitor (DPP4i), and sulfonylureas is limited.
Quantify the risk of hypoglycemia associated with SGLT2i, GLP1RA, DPP4i, and sulfonylureas (the primary reference group).
Retrospective cohort study conducted using electronic health records from Geisinger Health, Pennsylvania (2015-2019).
A total of 10,713 patients with type 2 diabetes who newly received SGLT2i (n=1487), GLP1RA (n=1241), DPP4i (n=2938), or sulfonylureas (n=5047). Propensity score-based inverse probability of treatment weighting was used to balance patient characteristics across four treatment groups simultaneously.
Hypoglycemia was defined as capillary blood glucose <70 mg/dL; severe hypoglycemia was defined as capillary blood glucose <54 mg/dL. A weighted Cox proportional hazards regression model was used to estimate the risk of outcomes for pairwise comparisons of SGTL2i, GLP1RA, DPP4i, and sulfonylureas.
Median follow-up was 21.3 months. Compared with sulfonylureas, the risk of hypoglycemia was lower with SGLT2i (hazard ratio 0.60 [95% confidence interval 0.48-0.75]), GLP1RA (0.49 [0.34-0.69]), and DPP4i (0.60 [0.48-0.78]). The risk of severe hypoglycemia was also lower with SGLT2i (0.43 [0.35-0.74]), GLP1RA (0.50 [0.28-0.87]), and DPP4i (0.64 [0.46-0.90]) compared to sulfonylureas. The risks of hypoglycemia and severe hypoglycemia were similar across the SGLT2i, GLP1RA, and DPP4i groups (SGLT2i vs. DPP4i: 0.95 [0.67-1.34]; GLP1RA vs. DPP4i: 0.81 [0.55-1.19]; SGLT2i vs. GLP1RA: 1.17 [0.76-1.82] for hypoglycemia).
SGLT2i and GLP1RA confer a lower risk of hypoglycemia compared with sulfonylureas and similar risk compared with DPP4i. Given the known cardiovascular benefits associated with SGLT2i and GL1PRA, our results suggesting the safety of SGLT2i and GL1PRA further support their use.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）和胰高血糖素样肽-1 受体激动剂（GLP1RA）在 2 型糖尿病中的应用日益广泛。低血糖是降糖药物的严重不良反应。SGLT2i、GLP1RA、二肽基肽酶-4 抑制剂（DPP4i）和磺酰脲类药物之间低血糖风险的真实世界比较有限。
量化 SGLT2i、GLP1RA、DPP4i 和磺酰脲类药物（主要参考组）相关低血糖风险。
利用宾夕法尼亚州盖辛格健康中心（2015-2019 年）的电子健康记录进行回顾性队列研究。
共纳入 10713 名新接受 SGLT2i（n=1487）、GLP1RA（n=1241）、DPP4i（n=2938）或磺酰脲类药物（n=5047）的 2 型糖尿病患者。采用基于倾向评分的逆概率治疗加权法同时平衡四组治疗患者的特征。
低血糖定义为毛细血管血糖<70mg/dL；严重低血糖定义为毛细血管血糖<54mg/dL。采用加权 Cox 比例风险回归模型估计 SGTL2i、GLP1RA、DPP4i 和磺酰脲类药物两两比较的结局风险。
中位随访时间为 21.3 个月。与磺酰脲类药物相比，SGLT2i（风险比 0.60 [95%置信区间 0.48-0.75]）、GLP1RA（0.49 [0.34-0.69]）和 DPP4i（0.60 [0.48-0.78]）降低低血糖风险。SGLT2i（0.43 [0.35-0.74]）、GLP1RA（0.50 [0.28-0.87]）和 DPP4i（0.64 [0.46-0.90]）降低严重低血糖风险。SGLT2i、GLP1RA 和 DPP4i 组低血糖（SGLT2i 与 DPP4i：0.95 [0.67-1.34]；GLP1RA 与 DPP4i：0.81 [0.55-1.19]；SGLT2i 与 GLP1RA：1.17 [0.76-1.82]）和严重低血糖（SGLT2i 与 DPP4i：0.96 [0.66-1.40]；GLP1RA 与 DPP4i：0.80 [0.52-1.25]；SGLT2i 与 GLP1RA：1.18 [0.77-1.81]）风险相似。
SGLT2i 和 GLP1RA 与磺酰脲类药物相比低血糖风险较低，与 DPP4i 相比低血糖风险相似。鉴于 SGLT2i 和 GL1PRA 与已知的心血管获益相关，我们的研究结果表明 SGLT2i 和 GL1PRA 具有安全性，这进一步支持了它们的应用。
