Two Gut Peptides May Predict Who Loses the Most Weight After Bariatric Surgery

This was a prospective study of 42 adults with severe obesity (32 RYGB, 10 SG). Postprandial responses of five gastrointestinal peptides — glicentin, oxyntomodulin, GLP-1, PYY, and ghrelin — were measured before and 6 months after surgery using meal tests. Food preferences and energy intake were assessed using a buffet meal test at both timepoints. Weight loss was measured at 18 months post-surgery.

Bariatric surgery doesn't work equally well for everyone, and doctors currently can't predict who will have the best outcomes. If oxyntomodulin and glicentin levels measured after surgery can identify patients who may struggle with weight loss, clinicians could provide earlier, more targeted support. These findings also shift attention from GLP-1 — the most-studied gut hormone — to two related but underappreciated peptides.

The GLP-1 drug revolution has focused attention on one gut hormone, but the gut produces many peptides that work together. This study suggests oxyntomodulin and glicentin — both derived from the same proglucagon gene as GLP-1 — may be more important for bariatric surgery outcomes than GLP-1 itself. This has implications for drug development, as oxyntomodulin-based therapies (like the dual agonist approach) could offer advantages over pure GLP-1 drugs.

The sample size was small (42 patients) with an unbalanced design (32 RYGB vs 10 SG), limiting the power to compare surgery types. The study was observational, so it cannot prove causation between hormone changes and weight loss. The 18-month follow-up may not capture long-term weight trajectory. The authors note these findings need replication.