Adding pioglitazone to metformin and an SGLT2 inhibitor may significantly improve glycaemic control in people with inadequately controlled type 2 diabetes mellitus (T2DM), according to a randomised clinical trial.
The phase 3 study included 249 patients with T2DM who were receiving metformin and dapagliflozin but had suboptimal glycaemic control. Participants received either pioglitazone 15 mg daily or placebo for 24 weeks.
At 24 weeks, HbA1c fell from 7.80% to 7.27% in the pioglitazone group, compared with a smaller reduction from 7.79% to 7.69% with placebo. The corrected between-group difference was −0.42 percentage points (p<0.001).
Greater Improvement in Glycaemic Targets
Moreover, 39.5% of patients receiving pioglitazone achieved an HbA1c below 7%, compared with 20.5% in the placebo group. Pioglitazone also reduced fasting plasma glucose and post-load glucose levels and improved insulin sensitivity.
As reported by Medical Dialogues, the findings suggest that pioglitazone could provide an additional option for patients who do not achieve adequate glycaemic control with metformin and an SGLT2 inhibitor.
Metabolic Benefits and Weight Gain
The treatment also increased adiponectin levels and improved certain lipid and liver-related parameters. However, patients receiving pioglitazone experienced modest weight gain. Body weight increased by approximately 1.37 kg over 24 weeks, while the placebo group experienced a reduction.
Overall, the researchers concluded that adding pioglitazone to metformin and dapagliflozin improved glycaemic and metabolic outcomes, with no significant difference in overall adverse events compared with placebo. However, the potential for weight gain should be considered when selecting therapy for individual patients.