Objective: To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%.
Methods: We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded.
Results: Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-β (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ≤3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients.
Conclusions: Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve β-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.
目的: 观察二甲双胍、沙格列汀、达格列净三联口服短期强化降糖治疗在9%≤HbA1c≤12%的新诊断2型糖尿病患者中的疗效及安全性。
方法: 共纳入新诊断的2型糖尿病患者58例，在糖尿病饮食和运动的基础上，给予二甲双胍+沙格列汀+达格列净口服治疗；治疗疗程为12周，记录患者治疗期间的指尖血糖，以及治疗前后下述效应指标改变值：糖化血红蛋白（HbA1c）、空腹血糖（FBG）/餐后2 h血糖（2 hPBG）、空腹胰岛素（FINS）/餐后2 h胰岛素（2 hPINS）、空腹C肽（F-CP）/餐后2 hC肽（2 hP-CP）、体质量（WT），并记录发生低血糖的次数以及不良事件。
结果: 12周治疗后，所有患者FBG、2 hPBG、HbA1c、HOMA-β、HOMAIR均较治疗前明显改善（P < 0.001），HbA1c下降值为（4.19±1.07）%，HbA1c < 7.0%的达标率达到83.33%；HbA1c下降的程度与FBG（r=0.487，P=0.000）、2 hPBG（r=0.310，P=0.023）、HOMA-β（r=-0.398，P=0.003）相关。治疗后体质量下降2.47±3.38 kg（P < 0.001），体质量指数（BMI）下降0.90±1.18 kg/m（2 P < 0.001），减重效果与患者基础体质量（r=0.678，P=0.000）、BMI（r=0.818，P=0.000）、F-CP（r=0.282，P=0.039）、HOMA-IR（r=0.297，P=0.029）相关。有8人发生低血糖症状10次（14.81%），确诊为低血糖症（血糖≤3.9 mmol/L）为3人，发生次数3次，低血糖发生率5.56%；无严重低血糖事件发生；无泌尿系及生殖系感染发生；2例因胃肠道反应不能耐受而退出实验；另2例患者因取药途径不便而退出实验；最后入组人数54例，男34例，女20例。
结论: 二甲双胍、沙格列汀、达格列净三联口服短期强化降糖方案在治疗新诊断的2型糖尿病患者（9%≤HbA1c≤12%）中可有效降糖，并有减重优势，低血糖风险小，以及有效改善β细胞胰岛素分泌功能，适合血糖较高的新诊断2型糖尿病患者临床应用。
Keywords: dapagliflozin; intensive treatment; sagliptin; triple regimen; type 2 diabetes.