Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.
Eur J Pharmacol. 2021 Jul 15;903:174145. doi: 10.1016/j.ejphar.2021.174145. Epub 2021 May 3.
Increased glucagon level was hypothesized to participate in the ketoacidosis associated with sodium-glucose co-transporter 2 inhibitors (SGLT2i) treatment. However, the effect of SGLT2i on glucagon remains controversial. Hence, we conducted this meta-analysis to assess the overall effect of SGLT2i treatment on plasma fasting glucagon level in patients with diabetes. PubMed/MEDLINE, Embase, and Cochrane databases were searched for studies published before August 2020. Clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus with reports of glucagon changes before and after SGLT2i intervention were included. Eligible trials were analyzed by fixed-effect model, random effect model, and meta-regression analysis accordingly. In total, ten trials were included in this meta-analysis. Compared with the non-SGLT2i treatment group, SGLT2i treatment resulted in increased plasma fasting glucagon levels with significance (WMD, 8.35 pg/ml; 95% CI, 2.17-14.54 pg/ml, P＜0.01) in patients with diabetes mellitus. Besides, when compared with non-SGLT2i control group, the insulin level decreased (WMD, -2.78 μU/ml; 95% CI, -5.11 to -0.46 μU/ml, P = 0.02) and ketone body level increased (WMD, 0.17 mmol/l; 95% CI, 0.09-0.25 mmol/l, P＜0.01) in patients with type 2 diabetes. In conclusion, our result indicated SGLT2i intervention would increase the plasma fasting glucagon level in patients with diabetes mellitus. The increase in plasma fasting glucagon level may be associated with reduced insulin level. The increased glucagon-insulin ratio after the use of SGLT2i may make diabetic patients susceptible to ketosis.
研究假设胰高血糖素水平升高参与了钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）治疗相关的酮症酸中毒。然而，SGLT2i 对胰高血糖素的影响仍存在争议。因此，我们进行了这项荟萃分析，以评估 SGLT2i 治疗对糖尿病患者空腹血浆胰高血糖素水平的总体影响。我们检索了发表于 2020 年 8 月之前的 PubMed/MEDLINE、Embase 和 Cochrane 数据库中的研究。纳入了报告 SGLT2i 干预前后胰高血糖素变化的 1 型和 2 型糖尿病患者的临床试验。相应地，通过固定效应模型、随机效应模型和荟萃回归分析对符合条件的试验进行了分析。本荟萃分析共纳入 10 项试验。与非 SGLT2i 治疗组相比，SGLT2i 治疗使糖尿病患者的血浆空腹胰高血糖素水平显著升高（WMD，8.35pg/ml；95%CI，2.17-14.54pg/ml，P＜0.01）。此外，与非 SGLT2i 对照组相比，胰岛素水平下降（WMD，-2.78μU/ml；95%CI，-5.11 至-0.46μU/ml，P=0.02），酮体水平升高（WMD，0.17mmol/l；95%CI，0.09-0.25mmol/l，P＜0.01）。总之，我们的结果表明 SGLT2i 干预会增加糖尿病患者的血浆空腹胰高血糖素水平。空腹胰高血糖素水平的升高可能与胰岛素水平降低有关。使用 SGLT2i 后胰高血糖素-胰岛素比值增加可能使糖尿病患者易发生酮症。
