Type 1 diabetes mellitus (T1DM) is characterized by autoimmune β-cell destruction and absolute insulin deficiency. While insulin remains the cornerstone of treatment, the adjunctive use of oral hypoglycemic agents (OHAs) has been explored, though clinical evidence in T1DM remains sparse. Mitochondrial dysfunction is increasingly recognized in the pathogenesis and complications of T1DM, and some OHAs are known to modulate mitochondrial pathways, primarily studied in type 2 diabetes mellitus. This review aimed to synthesize existing evidence regarding the roles of OHAs in T1DM, with a specific focus on their potential impact on mitochondrial function. Following PRISMA guidelines, eligible studies investigating mitochondrial dysfunction in T1DM or the effects of OHAs on mitochondrial function in T1DM were included. Of 997 articles screened, 24 studies met inclusion criteria. Twenty studies described the mechanisms of mitochondrial dysfunction in T1DM, highlighting oxidative stress, impaired ATP production, disrupted proteostasis, apoptosis, and altered mitochondrial dynamics. Four preclinical studies suggested that metformin and empagliflozin may improve mitochondrial quality control in an adenosine monophosphate-activated protein kinase (AMPK)-dependent manner by enhancing biogenesis and preventing mitochondrial fission in T1DM. Certain OHAs may modulate mitochondrial dysfunction in T1DM, but clinical translation remains speculative and requires further investigation regarding their potential as adjunctive therapy.
Cheng et al. (Wed,) studied this question.