Purpose of reviewThe metabolic signature associated with obesity is characterized by a decrease in plasma glycine concentration, a feature closely associated with insulin resistance and highly predictive of the risk of developing chronic metabolic diseases. This review presents recent advances in understanding the causes of decreased glycine availability and in targeting strategies to replenish the glycine pool and especially to improve insulin resistance.Recent resultsRecent literature has made progress in understanding host and gut microbiota mechanisms in determining circulating glycine levels. It has also explored new clinical pathways to restore circulating glycine levels and insulin resistance in obesity-related metabolic diseases.Recent findings suggest that glycine metabolism must now be considered in close interaction with branched-chain amino acid (BCAA) metabolism. Thus, strategies that decrease BCAAs seem to be the best to restore glycine. Furthermore, recent literature has confirmed that lifestyle strategies aimed at inducing weight loss are effective in replenishing the glycine pool. It also confirms that correcting the dysbiosis of the gut microbiota associated with obesity may be a valuable means of achieving this goal. However, it remains unclear whether dietary glycine is an effective strategy for correcting cardiometabolic disorders in obesity.