Fighting fire with fire: the need to use metformin to combat antipsychotic-induced weight gain and metabolic complications

Background:

Second-generation antipsychotics (SGAs) are moderately effective treatments for psychotic disorders but are associated with significant weight gain and metabolic complications. These contribute to a nearly 20-year reduction in life expectancy for individuals with enduring psychotic illness. Weight gain can also negatively impact adherence, increase relapse risk, and worsen psychosocial outcomes.

Aims:

To highlight the mechanisms underlying antipsychotic-induced weight gain (AIWG), examine pharmacological strategies for its prevention and treatment, and argue for the early use of metformin.

Method:

This perspective article synthesises current evidence on the pathophysiology of AIWG and evaluates the role of metformin in mitigating these effects.

Conclusions:

Weight gain can occur rapidly after initiating antipsychotic treatment, particularly in young people and those prescribed antipsychotics for non-psychotic indications. Presentation and response to interventions vary. Of all pharmacological strategies, metformin has the most robust evidence for both prevention and treatment of AIWG. It is a well-tolerated, low-cost antihyperglycaemic agent with an established safety profile. Metformin should be considered early in the course of antipsychotic treatment for all individuals, regardless of diagnosis, to prevent clinically significant weight gain and reduce long-term health risks. Early intervention may improve adherence, reduce relapse, and enhance overall quality of life.