Expert Consensus on the Clinical Use of the Dapagliflozin–Pioglitazone Fixed-Dose Combination in Adults with Type 2 Diabetes Mellitus in India: PRO-3 Study
Mathew John, Vijay K. Panikar, Krishna G. Seshadri, Mithun Bhartia, Ameya Joshi, Dakshata Padhye, Nitin Kapoor, Usha Ayyagari, I. Periyandavar, G. Vijayakumar, A. Shanmugam, Vijaya Bhaskar Reddy, N. K. Narayanan, M. V. Vimal, T. S. Boochandran, Thamburaj AnthuvanAbstract
Background:
Type 2 diabetes mellitus (T2DM) in Indian populations is characterized by early onset, progressive beta-cell dysfunction, marked insulin resistance, and a high burden of cardiometabolic comorbidities. While sodium–glucose cotransporter-2 inhibitors and thiazolidinediones offer complementary mechanisms targeting these defects, evidence guiding the clinical use of their fixed-dose combination (FDC) remains limited. The PRO-3 expert consensus was developed to provide evidence-informed, practice-oriented guidance for clinical use in India.
Objective:
We aimed to develop expert consensus on the clinical positioning of the dapagliflozin–pioglitazone combination in adults with T2DM.
Materials and Methods:
A structured, multi-phase modified Delphi approach was employed. Draft statements were developed through literature review and expert input. A national panel of 111 multidisciplinary experts evaluated 24 statements using an anonymized 5-point Likert scale. Consensus was predefined as ≥80% agreement. Statements not meeting consensus were revised and reevaluated in a second round, followed by final validation. Supporting evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation framework.
Results:
All 24 statements met the predefined consensus threshold; 21 achieved consensus in the initial round, whereas 3 required revision and re- evaluation. The recommendations address clinical rationale, patient selection, therapeutic positioning, comorbidity-specific considerations, safety, dose selection, monitoring, and integration with other glucose-lowering therapies. The panel supported a pathophysiology-oriented approach integrating insulin sensitization and organ-protective mechanisms, with consideration in individuals requiring treatment intensification and those with metabolic comorbidities, including overweight or obesity and metabolic dysfunction-associated steatotic liver disease.
Conclusions:
This India-specific expert consensus provides practical guidance on the clinical positioning of the dapagliflozin–pioglitazone FDC in the management of T2DM. In appropriately selected individuals, this combination may be considered as part of a treatment strategy that addresses both glycemic control and the underlying metabolic dysfunction associated with T2DM. However, further clinical and real-world evidence is needed to strengthen the evidence base and define its optimal role in clinical practice.