Yi Lin,1,* Jianxia Shi,1,* Xuemei Yu,2 Jiao Sun,3 Suo Lixia,4 Jiaqing Dou,5 Min Zhang,6 Xiaohua Li,7 Zhufang Tian,8 Hongyan Deng,9 Bo Feng,10 Qing Su,11 Yongde Peng1 

1Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Central Hospital of Fengxian District, Shanghai, People’s Republic of China; 3Huadong Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 4Shanghai Jiading Central Hospital, Shanghai Jiading Central Hospital, Shanghai, People’s Republic of China; 5Chaohu Hospital of Anhui Medical University, Chaohu, People’s Republic of China; 6Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, People’s Republic of China; 7Seventh People’s Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 8Xi‘an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 9Wuhan Fourth Hospital, Wuhan, People’s Republic of China; 10Dongfang Hospital Affiliated to Tongji University, Shanghai, People’s Republic of China; 11Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yongde Peng, Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, 100 haining Road, Shanghai, 200080, People’s Republic of China, Tel +86-13386259649, Email pengyongde0908@126.com

Aim: The aim of this study was to compare the efficacy and safety of fixed-dose combination (FDC) of pioglitazone and metformin supplemented with dapagliflozin (test group) with those of basal insulin supplemented with metformin (control group) in patients with inadequately controlled type 2 diabetes mellitus (T2DM).
Methods: This 16-week, prospective, randomized, open-label study enrolled patients aged 18– 75 years with glycated hemoglobin (HbA1c) levels between ≥ 8% and ≤ 11%. The primary endpoint was the proportion of patients who achieved HbA1c < 7% at week 16 without hypoglycemia or weight gain. The secondary endpoints included blood glucose, lipid profile, body weight, body mass index, inflammatory markers, bone Gla-protein, liver enzymes, and patient satisfaction.
Results: Among the full analysis set of 147 participants, no significant difference was observed in the primary endpoint between the test group and the control group. However, the test group had a higher percentage of patients who achieved HbA1c < 7% at week 16 without hypoglycemia and experienced a weight loss of ≥ 3% (31.51% vs 13.51%, P=0.009). Patients in the test group whose BMI≥ 24 kg/m2 also achieved a substantial achievement rate (36.73% vs 15.79%, P=0.014). The test group also exhibited a greater reduction in body weight and improvements in 2-hour postprandial glucose level, systolic blood pressure, and lipid profile. Notably, combination therapy did not increase the risk of hypoglycemia or weight gain. Patients in the test group were more satisfied than those in the control group with continuing to accept pioglitazone/metformin FDC combined with dapagliflozin.
Conclusion: In the absence of contraindications, pioglitazone/metformin FDC supplemented with dapagliflozin may serve as a safe and effective alternative to basal insulin combined with metformin for rectifying inadequate glucose control, as the former enables metabolic improvements without compromising safety.
Chinese Clinical Trial Registry Number: CHiCTR 2000036076. https://www.chictr.org.cn/showproj.html?proj=58825.

Keywords: dapagliflozin, pioglitazone/metformin FDC, type 2 diabetes, metformin, insulin