METFORMIN AND WEIGHT REDUCTION: A NARRATIVE REVIEW OF CONTEMPORARY EVIDENCE (2024–2025)

Abstract

Background:
Metformin, the cornerstone therapy for type 2 diabetes mellitus (T2DM), has demonstrated consistent weight-modulating properties beyond its glucose-lowering effects. Recent research (2024–2025) has expanded understanding of its metabolic and hormonal mechanisms influencing adiposity and insulin resistance.

Objective:
This review synthesizes recent randomized controlled trials (RCTs) and meta-analyses examining the efficacy, mechanisms, and safety of metformin in weight reduction among diabetic, prediabetic, and non-diabetic populations.

Methods:
A narrative synthesis was performed using systematic literature searches across PubMed, Scopus, ScienceDirect, and SpringerLink from January 2024 to November 2025. Studies were included if they were peer-reviewed RCTs or quasi-experimental trials evaluating metformin monotherapy or combination therapy for ≥12 weeks, with quantitative outcomes on body weight, BMI, or metabolic parameters. Fifteen studies, encompassing more than 2,000 participants, met inclusion criteria.

Results:
Metformin monotherapy achieved an average weight reduction of 3–5% (≈3.4 kg), while combination therapy with GLP-1 or SGLT2 inhibitors yielded superior outcomes (≈5–7 kg). Mechanistically, metformin activates AMPK, modulates gut microbiota—particularly Akkermansia muciniphila—and influences hypothalamic GLP-1 signaling to enhance satiety and lipid metabolism. The therapy was well tolerated, with gastrointestinal symptoms as the most frequent mild adverse event.

Conclusion:
Metformin remains a safe, cost-effective, and multi-mechanistic pharmacologic option for managing obesity and metabolic disorders. Its synergistic efficacy in combination regimens underscores its evolving role in modern metabolic and precision medicine.