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

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.To produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology.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.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.All 11 recommendations and 7 supporting good practice developed here were formulated de novo.These recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.