Department of Internal Medicine, University of Manitoba Max Rady College of Medicine, Winnipeg, Manitoba, Canada.
Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada
BMJ Open Diabetes Res Care. 2021 Dec;9(2). doi: 10.1136/bmjdrc-2021-002352.
Metformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control. As the choice of preferred second OHAs is less well defined, we sought to compare the real-world safety of sulfonylureas to other OHAs as add-on therapy to metformin in patients with T2D.
This retrospective cohort study included adults in Manitoba, Canada with T2D from 2006 to 2017. Using a new-user design, we divided patients who started on metformin into two groups: add-on therapy with a sulfonylurea and add-on therapy with a different OHA. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. We calculated propensity scores and applied inverse probability of treatment weights to each individual. We compared groups using Cox proportional hazards regression and explored differences in HRs between pre-2008 (acarbose, meglitinides, and thiazolidinediones) and post-2008 (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose linked transporter-2 inhibitors) OHAs.
Our cohort included 32 576 individuals (28 077 metformin plus sulfonylurea and 4499 metformin plus 'other'). Patients newly prescribed a sulfonylurea in the setting of metformin had a higher risk of all-cause mortality (HR 1.44, 95% CI 1.12 to 1.84, p=0.005) and major hypoglycemic episodes (HR 2.78, 95% CI 1.66 to 4.66, p<0.001) than those prescribed an 'other' OHA. No differences in cardiovascular events were observed (HR 0.99, 95% CI 0.81 to 1.22, p=0.92). In subgroup analyses, mortality and cardiovascular event risk was higher in patients prescribed sulfonylureas versus post-2008 OHAs.
Sulfonylureas as add-on therapy to metformin are associated with increased risk of all-cause mortality and major hypoglycemic episodes compared with 'other' OHAs. Post hoc analysis suggests newer OHAs may be preferred to sulfonylureas as second-line therapy for glycemic control.
二甲双胍是大多数 2 型糖尿病（T2D）患者的首选初始口服降糖药（OHA）。然而，通常需要不止一种药物才能实现最佳血糖控制。由于首选的第二种 OHA 的选择不太明确，我们试图比较磺酰脲类药物与其他 OHA 作为 T2D 患者二甲双胍附加治疗的真实世界安全性。
这项回顾性队列研究纳入了 2006 年至 2017 年期间加拿大马尼托巴省的 T2D 成年患者。使用新用户设计，我们将开始使用二甲双胍的患者分为两组：磺酰脲类药物附加治疗组和其他 OHA 附加治疗组。结局包括全因死亡率、心血管事件和严重低血糖事件。我们计算了倾向评分并为每个个体应用了治疗反概率权重。我们使用 Cox 比例风险回归比较了两组，并探索了 2008 年前（阿卡波糖、米格列醇和噻唑烷二酮）和 2008 年后（二肽基肽酶-4 抑制剂、胰高血糖素样肽-1 受体激动剂和钠-葡萄糖协同转运蛋白-2 抑制剂）OHA 之间 HR 的差异。
我们的队列包括 32576 名患者（28077 名接受二甲双胍加磺酰脲类药物治疗和 4499 名接受二甲双胍加“其他”OHA 治疗）。在接受二甲双胍治疗的情况下新处方磺酰脲类药物的患者全因死亡率（HR 1.44，95%CI 1.12 至 1.84，p=0.005）和严重低血糖事件（HR 2.78，95%CI 1.66 至 4.66，p<0.001）的风险高于接受“其他”OHA 治疗的患者。未观察到心血管事件的差异（HR 0.99，95%CI 0.81 至 1.22，p=0.92）。在亚组分析中，与 2008 年后的 OHA 相比，磺酰脲类药物治疗的患者死亡和心血管事件风险更高。
与其他 OHA 相比，磺酰脲类药物作为二甲双胍的附加治疗与全因死亡率和严重低血糖事件的风险增加相关。事后分析表明，新型 OHA 可能优于磺酰脲类药物作为血糖控制的二线治疗。
