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Native Oxyntomodulin Has Significant Glucoregulatory Effects Independent of Weight Loss in Obese Humans With and

Sudha S Shankar1, R Ravi Shankar2, Lori A Mixson2

  • 1Merck & Co., Inc., Kenilworth, NJ sudhashankar@comcast.net.

Diabetes
|March 17, 2018
PubMed

Insights

Oxyntomodulin (OXM) boosts insulin secretion and improves glucose control in obese individuals with and without type 2 diabetes. This hormone shows potential for managing hyperglycemia through enhanced insulin release and weight loss.

Area of Science:

  • Endocrinology
  • Metabolism
  • Pharmacology

Background:

  • Oxyntomodulin (OXM) is an enteroendocrine hormone known for appetite suppression and weight loss effects.
  • Its impact on glucose homeostasis and insulin secretion requires further elucidation.
  • Obesity and type 2 diabetes mellitus (T2DM) are associated with significant metabolic dysregulation.

Purpose of the Study:

  • To investigate the acute effects of native Oxyntomodulin (OXM) on insulin secretion rates (ISRs) and glycemic excursion.
  • To compare OXM's efficacy with placebo and a GLP-1 analog (liraglutide) in obese subjects with and without T2DM.

Main Methods:

  • Two randomized, placebo-controlled, single-dose crossover trials were conducted.
  • Intravenous infusion of native OXM during a graded glucose infusion (GGI) procedure.
  • Measurements included ISR and glycemic excursion in overweight/obese subjects without diabetes and obese subjects with T2DM.

Main Results:

  • Native OXM significantly increased ISR and blunted glycemic excursion in both obese groups compared to placebo.
  • In T2DM subjects, OXM's effects were comparable to liraglutide, restoring beta-cell responsiveness.
  • These effects were observed acutely and were independent of weight loss.

Conclusions:

  • Native OXM acutely augments glucose-dependent insulin secretion in obese individuals, with or without diabetes.
  • OXM demonstrates potential for improving hyperglycemia through enhanced insulin secretion and weight loss.
  • Its efficacy is comparable to pharmacologic GLP-1 receptor activation.

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