This paper reports a case of a patient with type 2 diabetes mellitus (T2DM) who had poor blood-glucose control. Based on the previous oral administration of metformin, acarbose, and glimepiride, semaglutide and ertugliflozin were added. After the first injection of semaglutide, the patient presented with symptoms such as anorexia, nausea, and fatigue. After the second injection of semaglutide, the anorexia and fatigue worsened, and new symptoms including nausea, vomiting, acid reflux, abdominal distension, and muscle soreness emerged. Laboratory findings revealed severe acidosis (pH 6.698), markedly reduced serum bicarbonate (2.4 mmol·L^-1), elevated blood glucose (15.54 mmol·L^-1), significantly elevated blood ketones (HI), and urine ketones (+++), leading to a diagnosis of severe diabetic ketoacidosis (DKA). Considering the medical and medication history, it was considered that these were adverse reactions caused by semaglutide and ertugliflozin. After discontinuing these two drugs and providing insulin-based hypoglycemic treatment and symptomatic supportive treatment, the patient's condition improved. During the six-month follow-up period, no DKA-related symptoms reappeared. Using the Naranjo's Assessment Scale, the association was deemed "probable" for semaglutide and ertugliflozin-induced DKA. Severe anorexia caused by semaglutide likely led to insufficient carbohydrate intake, exacerbated by ertugliflozin’s glucosuric effect, precipitating profound energy deficit and DKA. This case alerts medical staff to inform patients of the possible DKA risk when using semaglutide and ertugliflozin in combination for the treatment of T2DM. During the treatment, blood glucose, ketone bodies and other indicators should be regularly monitored. Once ketoacidosis is suspected, the drugs should be immediately discontinued and treatment should be initiated.

1.王思骅, 汪盛, 王岩, 等. 司美格鲁肽治疗2型糖尿病的快速卫生技术评估[J]. 中国药房, 2023, 34(12): 1503-1508. [Wang SH, Wang S, Wang Y, et al. Semaglutide in the treatment of type 2 diabetes mellitus: rapid health technology assessment[J]. China Pharmacy, 2023, 34(12): 1503-1508.] DOI: 10.6039/j.issn.1001-0408.2023.12.18.

2.蒋王艳, 刘少华, 郭洁茹, 等. 基于美国FAERS数据库的司美格鲁肽不良事件信号挖掘[J]. 药物流行病学杂志, 2022, 31(3): 167-172, 197. [Jiang WY, Liu SH, Guo JR, et al. Data mining for adverse drug events of semaglutide based on FAERS database[J]. Chinese Journal of Pharmacoepidemiology, 2022, 31(3): 167-172, 197.] DOI: 10.19960/j.cnki.issn1005-0698.2022. 03.005.

3.程钱, 邹舒鹏, 孙明辉. 新一代钠-葡萄糖共转运体-2抑制剂艾托格列净在糖尿病及特殊人群中的治疗价值[J]. 中国新药杂志, 2023, 32(11): 1099-1107. [Cheng Q, Zou SP, Sun MH. Clinical therapeutic value of a new generation of sodium-glucose cotransporter-2 inhibitor ertugliflozin in patients with diabetes and special populations[J]. Chinese Journal of New Drugs, 2023, 32(11): 1099-1107.] DOI: 10.3969/j.issn.1003-3734. 2023.11.004.

4.胡燕红, 付薇. 艾托格列净联合司美格鲁肽治疗2型糖尿病合并心衰患者的临床疗效观察[J]. 药品评价, 2024, 21(1): 68-71. [Hu YH, Fu W. Clinical efficacy of ertugliflozin combined with semaglutide in the treatment of type 2 diabetes patients with heart failure[J]. Drug Evaluation, 2024, 21(1): 68-71.] DOI: 10.19939/j.cnki.1672-2809.2024.01.16.

5.Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions[J]. Clin Pharmacol Ther, 1981, 30(2): 239-245. DOI: 10.1038/clpt.1981.154.

6.国家药品监督管理局.关于发布个例药品不良反应收集和报告指导原则的通告[EB/OL]. (2018-12-19)[2023-04-06]. https://www.nmpa.gov.cn/xxgk/ggtg/ypggtg/ypqtggtg/ 20181221172901438.html.

7.Bhanushali KB,Asnani HK,Nair A,et al.Pharmacovigilance study for SGLT 2 inhibitors-safety review of real-world data & randomized clinical trials[J]. Curr Probl Cardiol, 2024, 49(9): 102664. DOI: 10.1016/j.cpcardiol.2024.102664.

8.李杰, 蒋志涛, 张月婵, 等. 钠-葡萄糖共转运蛋白2抑制剂致酮症酸中毒的风险分析[J]. 临床药物治疗杂志, 2022, 20(1): 53-56. [Li J, Jiang ZT, Zhang YC, et al. Analysis of ketoacidosis caused by sodium-glucose cotransporter 2 inhibitors[J]. Clinical Medication Journal, 2022, 20(1): 53-56.] DOI: 10.3969/j.issn.1672-3384.2022.01.006.

9.Wu T, Zhang Y, Shi Y, et al. Safety of glucagon-like peptide-1 receptor agonists: a real-world study based on the US FDA Adverse Event Reporting System Database[J]. Clin Drug Investig, 2022, 42(11): 965-975. DOI: 10.1007/s40261-022-01202-1.

10.赵雪, 李凡, 张彦丽, 等. 度拉糖肽和恩格列净联用致糖尿病酮症酸中毒[J]. 药物不良反应杂志, 2022, 24(3): 147-149. [ Zhao X, Li F, Zhang YL, et al. Diabetic ketoacidosis induced by combination use of dulaglutide and empagliflozin[J]. Adverse Drug Reactions Journal, 2022, 24(3): 147-149.] DOI: 10.3760/cma.j.cn114015-20210401-00399.

11.刘敏, 苏娜, 徐珽. 钠-葡萄糖共转运蛋白2抑制剂引发糖尿病酮症酸中毒机制的研究进展[J]. 中国医院药学杂志, 2018, 38(3): 330333. [Liu M, Su N, Xu T. Advances in mechanisms of diabetic ketoacidosis induced by SGLT2 inhibitors[J]. Chinese Journal of Hospital Pharmacy, 2018, 38(3): 330333.] DOI: 10.13286/j.cnki.chinhosppharmacyj.2018.03.27.

12.严颐丹, 施芳红. SGLT2抑制剂引起酮症酸中毒的机制及处理[J]. 中国医院药学杂志, 2018, 38(14): 15631565. [Yan YD, Shi FH. Basic mechanisms and management of ketoacidosis induced by SGLT2 inhibitors[J]. Chinese Journal of Hospital Pharmacy, 2018, 38(14): 15631565.] DOI: 10.13286/j.cnki.chinhosppharmacyj.2018.14.27.

13.Blundell J, Finlayson G, Axelsen M, et al. Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity[J]. Diabetes Obes Metab, 2017, 19(9): 1242-1251. DOI: 10.1111/dom.12932.

14.蔡俊, 崔雯霞, 高蕾, 等. 钠-葡萄糖共转运蛋白2抑制剂致围术期非高血糖型酮症酸中毒文献病例分析[J]. 药物不良反应杂志, 2020, 22(9): 505510. [Cai J, Cui WX, Gao L, et al. Literature case analysis of perioperative euglycemic diabetic ketoacidosis induced by sodium-glucose cotransporter 2 inhibitors[J]. Adverse Drug Reactions Journal, 2020, 22(9): 505510.] DOI: 10.3760/cma.j.cn114015-20191120-00928.

15.Kovacich N, Chavez B. Ertugliflozin (Steglatro): a new option for SGLT2 inhibition[J]. PT., 2018, 43(12): 736-742. https://pubmed.ncbi.nlm.nih.gov/30559584/.

16.齐艳霞, 张冬燕, 冯静, 等.钠-葡萄糖共转运蛋白2抑制剂相关酮症/酮症酸中毒的文献分析[J]. 河南医学研究, 2023, 32(14): 2510-2512. [Qi YX, Zhang DY, Feng J, et al. Literature analysis of sodium-glucose cotransporter 2 inhibitor related ketosis/ketoacidosis[J]. Henan Medical Research, 2023, 32(14): 2510-2512.] DOI: 10.3969/j.issn.1004-437X.2023.14.004.

17.Chandrakumar HP, Chillumuntala S, Singh G, et al. Postoperative euglycemic ketoacidosis in type 2 diabetes associat ed with sodium-glucose cotransporter 2 inhibitor: insights into pathogenesis and management strategy[J]. Cureus, 2021, 13(6): e15533. DOI: 10.7759/cureus.15533.

18.司海娇, 肇丽梅, 蔡爽, 等. 胰高血糖素样肽1受体激动剂类药物用药指导（2023版）[J]. 中国药房, 2023, 34(11): 1281-1292. [Si HJ, Zhao LM, Cai S, et al.Medication guidelines for glucagon-like peptide-1 receptor agonist (2023 edition)[J]. China Pharmacy, 2023, 34(11): 1281-1292.] DOI: 10.6039/j.issn.1001- 0408.2023.11.01.

19.中华医学会糖尿病学分会.中国2型糖尿病防治指南（2020年版）（上）[J]. 中国实用内科杂志, 2021, 41(8): 668-695. [Chinese Diabetes Society. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition) (Part  1)[J]. Chinese Journal of Practical Internal Medicine, 2021, 41(8): 668-695.] DOI: 10.19538/j.nk2021080106.

20.中华医学会内分泌学分会, 中华医学会糖尿病学分会. 胰高糖素样肽-1(GLP-1)受体激动剂用于治疗2型糖尿病的临床专家共识[J]. 中华内科杂志, 2020, 59(11): 836-846. [Chinese Society of Endocrinology, Chinese Diabetes Society. Consensus recommendations on utilizing glucagon-like peptide-1(GLP-1) receptor agonists in the treatment of type 2 diabetes mellitus[J]. Chinese Journal of Internal Medicine, 2020, 59(11): 836-846.]DOI: 10.3760/cma.j.cn112138-20200704-00646.