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GLP-1 Not As Effective after Roux-en-Y Gastric Bypass

Researchers compared glucose and hormonal responses to a liquid meal test in 20 obese participants with T2 who underwent RYGB or nonsurgical intensive lifestyle modification…

Rapid glycemic improvements following Roux-en-Y gastric bypass (RYGB) are frequently attributed to the enhanced GLP-1 response, but causality remains unclear. To determine the role of GLP-1 in improved glucose tolerance after surgery, the study compared glucose and hormonal responses to a liquid meal test in 20 obese participants with type 2 diabetes mellitus who underwent RYGB or nonsurgical intensive lifestyle modification (ILM) (n = 10 per group) before and after equivalent short-term weight reduction.

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The GLP-1 receptor antagonist exendin(9-39)-amide (Ex-9) was administered, in random order and in double-blinded fashion, with saline during two separate visits after equivalent weight loss.

Despite the markedly exaggerated GLP-1 response after RYGB, changes in postprandial glucose and insulin responses did not significantly differ between groups, and glucagon secretion was paradoxically augmented after RYGB. Hepatic insulin sensitivity also increased significantly after RYGB.
With Ex-9, glucose tolerance deteriorated similarly from the saline condition in both groups, but postprandial insulin release was markedly attenuated after RYGB compared with ILM. GLP-1 exerts important insulinotropic effects after RYGB and ILM, but the enhanced incretin response plays a limited role in improved glycemia shortly after surgery. Instead, enhanced hepatic metabolism, independent of GLP-1 receptor activation, may be more important for early postsurgical glycemic improvements.

Practice Pearls:

  • Researchers compared 20 patients with obesity and type 2 diabetes who underwent Roux-en-Y gastric bypass (RYGB) or intensive lifestyle modification to determine the association of GLP-1 with glucose tolerance.
  • Differences in postprandial glucose and insulin responses were not observed between groups even though GLP-1 response was increased after RYGB. RYGB was also associated with increased hepatic insulin sensitivity.
  • Researchers suggest that glycemic improvements often observed following RYGB may be explained by improved hepatic metabolism rather than GLP-1 receptor activation.

ML Vetter. Diabetes 2015 Feb 01;64(2)434-446