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Glucose-Dependent Insulinotropic Polypeptide and Glucagon After Weight Loss Induced by Diet or Bariatric Surgery

Amanda Finn¹, Yenni Cedillo¹, Marthe Aukan²

¹Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Obesity (Silver Spring, Md.)

|September 30, 2025

Abstract

Objective:

This study compared the effects of a very low-energy diet (VLED), alone or combined with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB), on glucose-dependent insulinotropic polypeptide (GIP) and glucagon concentrations, hormones likely to play a role in weight loss maintenance.

Methods:

Participants with severe obesity underwent 10 weeks of VLED alone (n = 15) or combined with SG (n = 15) or RYGB (n = 14). Plasma concentrations of glucagon and GIP (fasting and the first 60 min of a meal), insulin sensitivity, respiratory quotient, and resting energy expenditure (REE) were measured at pre- and post-intervention. Differences in hormone concentrations between groups at follow-up and associations between hormones and metabolic outcomes were evaluated.

Results:

Fasting glucagon concentrations were higher, while postprandial GIP concentrations were lower, after RYGB compared to SG. An increase in postprandial glucagon was associated with a decrease in Matsuda index in the RYGB group and with an increase in REE in all groups. An increase in fasting GIP was correlated with an increase in HOMA-IR.

Conclusions:

RYGB was associated with lower postprandial GIP and greater glucagon concentrations compared with other groups. These hormonal changes are likely to impact REE, as well as insulin sensitivity, potentially modulating the likelihood of weight loss maintenance.

Trial Registration:

ClinicalTrials.gov identifier NCT04051190.

Keywords:

GIP bariatric surgery glucagon obesity

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