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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...

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Randomized Controlled Trial to Study the Acute Effects of Strength Exercise on Insulin Sensitivity in Obese Adults

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Improved Glucagon Sensitivity Following Weight Loss: A Systematic Review and Meta-Analysis.

Hye-Rin Charlotte Kim¹, Lima Hamidi², Anne Majumdar^1,3

¹Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.

Obesity Reviews : an Official Journal of the International Association for the Study of Obesity

|May 19, 2026

Summary

Weight loss significantly reduces fasting glucagon and alanine levels in individuals with obesity. This indicates improved liver sensitivity to glucagon and a better-regulated liver-alpha-cell axis following weight reduction.

Keywords:

bariatric surgery glucagon obesity weight loss

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Randomized Controlled Trial to Study the Acute Effects of Strength Exercise on Insulin Sensitivity in Obese Adults

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Area of Science:

Metabolic Health
Endocrinology
Obesity Research

Background:

Obesity is linked to glucagon resistance, impacting metabolic regulation.
Fasting plasma glucagon and alanine are key biomarkers for assessing glucagon resistance.
Understanding the effects of weight loss on these biomarkers is crucial for metabolic health.

Purpose of the Study:

To systematically review and meta-analyze the impact of weight loss in obese individuals on fasting plasma glucagon and alanine.
To evaluate the association between the magnitude of weight loss and changes in these biomarkers.

Main Methods:

Comprehensive literature search of Medline and Embase databases.
Inclusion of 47 studies with 2061 participants and 69 interventions.
Application of random-effects meta-analyses, correlation analyses, and risk of bias assessments.

Main Results:

Mean weight loss across studies was -18.23 kg.
Significant reductions observed in fasting glucagon (-4.05 pmol/L) and alanine (-17.9%) post-weight loss.
Weight loss interventions, including surgical, dietary, and pharmacological, all led to glucagon reduction.

Conclusions:

Weight loss is associated with significant decreases in fasting glucagon and alanine.
These findings suggest enhanced hepatic glucagon sensitivity.
Weight loss contributes to the partial restoration of the liver-alpha-cell axis.