Abstract Antipsychotic drugs exert their therapeutic effects through dopamine D 2 -like receptor blockade but are also associated with clinically significant dysglycaemia. Whether these metabolic effects reflect consistent actions on peripheral dopaminergic targets, including pancreatic β-cell D 2 -like receptors, remains uncertain. We conducted a systematic review and meta-analysis of preclinical in vitro and ex vivo studies examining the effects of dopamine, D 2 -like receptor agonists and antagonists on insulin secretion in isolated pancreatic islets or β-cell lines. PubMed, Embase, and PsycINFO were searched from inception to Sept 22, 2025. Two reviewers independently screened studies, extracted data, and performed random-effects meta-analyses with subgroup and meta-regression analyses assessing glucose concentration, compound type, and dose. 39 studies met inclusion criteria, with 37 included in the metanalysis. Dopamine and D 2 -like receptor agonists showed no significant effect under low-glucose conditions but robustly inhibited glucose-stimulated insulin secretion (GSIS) in rodent and rabbit models (g = –2.36; 95% CI: –2.77 to –1.96; P < 0.0001 95% CI − 2.88 to −1.09; p < 0.0001 respectively), with greater GSIS suppression at higher glucose concentrations and dopamine doses. Though D 2 -like receptor antagonists alone had no significant effect (g = –0.25, 95% CI –0.68 to 0.18, P = 0.25), these drugs blocked GSIS inhibiton by co-administered dopamine (g = 1.59 0.76 to 2.42; p = 0.0002). These findings demonstrate that D 2 -like receptor activation inhibits pancreatic β-cell insulin secretion in a glucose- and dose-dependent manner, whereas receptor blockade reverses this effect, identifying a peripheral dopaminergic mechanism that may contribute to antipsychotic drug-associated dysglycaemia independent of weight gain. Together, these findings highlight the need for metabolic monitoring beyond weight alone in response to treatment with antipsychotic medications.
Al‐Hasani et al. (Mon,) studied this question.