Evaluating iPSC-based interventions for diabetes: a systematic review and meta-analysis.

Abstract

Background: Diabetes mellitus (DM) is characterized by progressive β-cell dysfunction, and current therapies improve glycemic control without restoring endogenous β-cell mass. Induced pluripotent stem cell (iPSC)-based approaches offer a potential regenerative strategy. This systematic review and meta-analysis evaluates the efficacy and safety of iPSC-based interventions for diabetes in preclinical models.

Methods: A comprehensive literature search was conducted in PubMed, ScienceDirect, and Web of Science for studies published up to November 2025. Studies assessing iPSC-based therapies in diabetic models were systematically reviewed and quantitatively synthesized.

Result: Thirty-one preclinical studies involving 424 animals were included. iPSC-based interventions were associated with reduced mortality (odds ratio [OR] 0.14) and reductions in blood glucose across 21 studies (mean difference [MD]  -267.36). Glucose-lowering effects were observed under fasting, non-fasting, and glucose-challenge conditions and were accompanied by increased insulin and C-peptide levels. Improvements were also reported in several diabetes-related complications, including cardiac dysfunction, impaired wound healing, neuropathy, and retinopathy.

Conclusion: iPSC-based therapies show potential to improve glycemic control and diabetes-related complications in preclinical models, likely through a combination of endocrine replacement and paracrine-mediated regenerative mechanisms. However, substantial heterogeneity across outcome assessments, reliance on short- to mid-term follow-up, and limitations of experimental disease models constrain the interpretation and generalizability of these findings. Immune compatibility, long-term safety, and scalable manufacturing remain key challenges for clinical translation.