Metformin in the management of antipsychotic-induced weight gain in adults with psychosis: development of the first evidence-based guideline using GRADE methodology.

Background: Adjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin's place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication.

Objective: To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology.

Methods: A list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be 'adopted or adapted' from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008-2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Findings: We confirmed that no published guideline-of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs.

Conclusion: All 11 recommendations and 7 supporting good practice developed here were formulated de novo.

Clinical implications: These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.