Aims

Patients undergoing insulin-based therapy for type 1 diabetes often experience poor glycemic control characterized by significant fluctuations. This study was undertaken to analyze the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2Is), as an adjunct to insulin, on time in range (TIR) and glycemic variability in patients with type 1 diabetes, using continuous glucose monitoring (CGM). In addition, we examined which type of SGLT2I yielded a superior effect compared to others.

Methods

We conducted a comprehensive search of PubMed, EMBASE, the Cochrane Library, Web of Science, and clinical trial registry websites, retrieving all eligible randomized clinical trials (RCTs) published up until February 2023. We analyzed the mean TIR, mean amplitude of glucose excursions (MAGE), mean daily glucose (MDG), diabetic ketoacidosis (DKA), standard deviation (SD), total insulin dose, and severe hypoglycemia to evaluate the efficacy and safety of SGLT2Is. A random-effects model was also employed.

Results

This study encompassed 15 RCTs. The meta-analysis revealed that the use of SGLT2Is as an adjuvant therapy to insulin led to a significant increase in TIR (MD = 10.78, 95%CI = 9.33–12.23, I² = 42 %, P < 0.00001) and a decrease in SD (MD = −0.38, 95%CI = −0.50 to −0.26, I² = 0 %, P < 0.00001), MAGE (MD = −0.92, 95%CI = −1.17 to −0.67, I² = 19 %, P < 0.00001), MDG(MD = −1.01, 95%CI = −1.32 to −0.70, I² = 48 %, P < 0.00001), and total insulin dose (MD = −5.81, 95%CI = −7.81 to −3.82, I² = 32 %, P < 0.00001). No significant increase was observed in the rate of severe hypoglycemia (RR = 1.04, 95 % CI = 0.76–1.43, P = 0.80). However, SGLT2I therapy was associated with increased DKA occurrence (RR = 2.79, 95 % CI = 1.42–5.48; P = 0.003, I² = 16 %). In addition, the subgroup analyses based on the type of SGLT2Is revealed that dapagliflozin might exhibit greater efficacy compared to other SGLT2Is across most outcomes.

Conclusions

SGLT2Is exhibited a positive effect on improving blood glucose level fluctuations. Subgroup analysis showed that dapagliflozin appeared to have more advantages. However, giving due consideration to preventing adverse effects, particularly DKA, is paramount.

Registration

Prospero CRD42023408276.

中文翻译：

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通过连续血糖监测评估钠-葡萄糖协同转运蛋白 2 抑制剂作为胰岛素辅助药物对 1 型糖尿病患者的影响：系统评价和荟萃分析

目标

接受基于胰岛素的 1 型糖尿病治疗的患者常常会出现血糖控制不佳、波动较大的情况。本研究旨在使用连续血糖监测 (CGM) 来分析钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT2Is) 作为胰岛素的辅助药物对 1 型糖尿病患者的作用时间范围 (TIR) 和血糖变异性的影响。此外，我们还检查了哪种类型的 SGLT2I 与其他类型相比产生了更好的效果。

方法

我们对 PubMed、EMBASE、Cochrane 图书馆、Web of Science 和临床试验注册网站进行了全面搜索，检索了截至 2023 年 2 月发布的所有符合条件的随机临床试验 (RCT)。我们分析了平均 TIR、平均血糖波动幅度(MAGE)、平均每日血糖 (MDG)、糖尿病酮症酸中毒 (DKA)、标准差 (SD)、总胰岛素剂量和严重低血糖来评估 SGLT2Is 的有效性和安全性。还采用了随机效应模型。

结果

这项研究包含 15 项随机对照试验。荟萃分析显示，使用 SGLT2Is 作为胰岛素的辅助治疗导致 TIR 显着增加（MD = 10.78，95%CI = 9.33–12.23，I 2 = 42 %，P < 0.00001）^， 并且TIR 降低SD（MD = -0.38，95%CI = -0.50 至 -0.26，I ²  = 0%，P  < 0.00001），MAGE（MD = -0.92，95%CI = -1.17 至 -0.67，I ²  = 19% ，P  < 0.00001)、MDG(MD = -1.01，95%CI = -1.32 至 -0.70，I ²  = 48 %，P < 0.00001) 和总胰岛素剂量 (MD = -5.81，95%CI = -7.81至-3.82，I ²  = 32%，P < 0.00001）。严重低血糖发生率未观察到显着增加（RR = 1.04，95% CI = 0.76–1.43，P  = 0.80）。然而，SGLT2I 治疗与 DKA 发生率增加相关（RR = 2.79，95 % CI = 1.42–5.48；P  = 0.003，I ²  = 16 %）。此外，基于 SGLT2Is 类型的亚组分析表明，在大多数结果中，与其他 SGLT2Is 相比，达格列净可能表现出更高的疗效。

结论

SGLT2Is 对改善血糖水平波动具有积极作用。亚组分析显示达格列净似乎具有更多优势。然而，适当考虑预防不良反应（尤其是 DKA）至关重要。

登记

普洛斯彼罗 CRD42023408276。