Summary: In adults with inadequately controlled type 2 diabetes (HbA1c 8 to 11 percent), a fixed-dose combination of pioglitazone/metformin plus dapagliflozin was compared with basal insulin plus metformin over 16 weeks. The primary endpoint, the proportion reaching HbA1c below 7 percent without hypoglycaemia or weight gain, did not differ significantly (43.84 percent versus 37.84 percent). Secondary metabolic measures favoured the oral regimen.
PICO Summary
| Element | Detail |
|---|---|
| Population | 147 adults (full analysis set), aged 18 to 75 years, with type 2 diabetes inadequately controlled (HbA1c 8 to 11 percent); 16-week, prospective, randomised, open-label, multicentre trial in China (CHiCTR2000036076). |
| Intervention | Fixed-dose pioglitazone/metformin supplemented with dapagliflozin (test group). |
| Comparison | Basal insulin supplemented with metformin (control group). |
| Outcome | Primary (not met): proportion achieving HbA1c below 7 percent at week 16 without hypoglycaemia or weight gain, 43.84 percent (test) versus 37.84 percent (control), no significant between-group difference. Secondary: a composite of target HbA1c without hypoglycaemia plus weight loss of 3 percent or more favoured the test group (31.51 percent versus 13.51 percent, p=0.009), as did the subgroup with BMI 24 or higher (36.73 percent versus 15.79 percent, p=0.014). The test group also showed greater reductions in body weight, 2-hour postprandial glucose, systolic blood pressure and lipids, without increased hypoglycaemia or weight gain. No 95 percent CI, absolute risk reduction or number needed to treat were reported in the abstract. |
Pio/Met + Dapagliflozin vs Basal Insulin
RCT · type 2 diabetes · 16 weeks
The oral pioglitazone/metformin plus dapagliflozin regimen did not beat basal insulin plus metformin on the primary glycaemic target without hypoglycaemia or weight gain. Secondary metabolic measures favoured the oral combination but are hypothesis-generating.
Expert Commentary
This trial should be read as a negative study on its own terms. The pre-specified primary endpoint was not met: the oral pioglitazone/metformin plus dapagliflozin regimen did not significantly outperform basal insulin plus metformin for the composite of glycaemic target without hypoglycaemia or weight gain. The favourable secondary findings, including the composite incorporating weight loss and the reductions in postprandial glucose, blood pressure and lipids, are biologically coherent and consistent with the known weight-neutral-to-favourable profile of this oral combination, but they are secondary and hypothesis-generating rather than confirmatory. The most important limitation is the open-label design, which is highly susceptible to bias in patient-reported satisfaction and in management decisions, and is compounded by a short 16-week horizon and modest sample. Can I use this with my patients? Cautiously, for a patient with type 2 diabetes inadequately controlled on metformin who is reluctant to start or intensify insulin and who has no contraindication to pioglitazone, this offers reassurance that an oral intensification path is a reasonable alternative, though it is not shown to be superior. Larger, blinded, longer trials with cardiovascular and durability endpoints are needed before this is positioned as a preferred strategy over insulin.
References
Lin Y, Shi J, Yu X, Sun J, Lixia S, Dou J, et al. Enhancing diabetes treatment: comparing pioglitazone/metformin with dapagliflozin versus basal insulin/metformin in type 2 diabetes. Drug Des Devel Ther. 2025;19:1795-1808. doi:10.2147/DDDT.S512872