In a major new narrative review, researchers reveal how changes in gut hormones affect people with obesity and type 2 diabetes (T2DM). The review shows that the gastrointestinal system plays a powerful role in weight, appetite and blood sugar control. This could reshape how doctors treat metabolic diseases worldwide.
The study, “Gut Peptide Alterations in Type 2 Diabetes and Obesity: A Narrative Review”, was published on 23 January 2026 in Current Obesity Reports and is freely available online. It explains how hormones from the gut influence metabolism and outlines why future therapies could focus more on hormonal regulation than on diet alone.
Most people think of the gut as simply breaking down food. But research shows it also acts as a major endocrine organ. It produces hormones, called gut peptides, that help regulate metabolism, hunger and blood glucose levels. In healthy bodies, these peptides balance energy use and appetite. However, in obesity and T2DM, this balance shifts. That fuels metabolic dysfunction.
For example, glucagon-like peptide-1 (GLP-1) is a hormone that helps insulin release, slows digestion and curbs appetite. In people with obesity or T2DM, the gut still produces GLP-1, but bodily response is weaker. Glucose-dependent insulinotropic polypeptide (GIP), another hormone, also loses effectiveness in these conditions.
As a result, even after eating, the signals that should prompt satiety and insulin release do not work well. Consequently, blood sugar stays high and hunger persists. This explains why people with T2DM and obesity often struggle to manage weight and glucose levels through lifestyle changes alone.
The review looked not only at well-known hormones like GLP-1 and GIP. It also examined others such as oxyntomodulin, glicentin, peptide YY (PYY), cholecystokinin (CCK), secretin, amylin, ghrelin and obestatin. These lesser-studied peptides also influence appetite, digestion speed and energy use.
For instance, PYY normally rises after meals to signal fullness. In obesity, this response weakens. Ghrelin, known as the “hunger hormone,” often drops in individuals with obesity, yet they still feel hungry. That paradox highlights just how complex metabolic signalling can be.
This hormonal picture helps explain why certain modern treatments succeed. Medications that mimic GLP-1 effects, called GLP-1 receptor agonists, have transformed diabetes care in recent years. They boost insulin production, reduce appetite and support weight loss. Newer drugs combine GLP-1 and GIP actions, offering further benefits.
The review suggests that treatments targeting multiple hormones might deliver even better outcomes. However, researchers stress that fully understanding how these hormones interact remains a priority. They argue that clinicians should not only treat high glucose and excess weight.
They should also aim to correct the hormonal signals that contribute to metabolic diseases.
The researchers examined hormone levels both when fasting and after meals. They compared mixed-meal tests (MMTs) with oral glucose tolerance tests (OGTTs). These tests show how hormone responses differ depending on what is eaten. For example, a carbohydrate-rich drink triggers different hormonal responses than a full meal. Such insights may influence future clinical testing and diagnosis.
Crucially, the article highlights that hormone alterations in people with T2DM or obesity are not uniform. Some hormones show increased levels, but their action may be impaired. Others show diminished release after eating. These patterns emphasise why a “one size fits all” approach to treatment often fails.
Despite the advances, the authors note significant gaps in understanding. Many hormones remain poorly studied, especially outside laboratory settings.
Researchers must standardise measurement methods so that studies are comparable. They also need bigger clinical trials to test new therapies based on gut peptides.
For example, oxyntomodulin and glicentin could offer dual benefits by promoting satiety and increasing energy expenditure. Yet only a handful of studies have looked at their clinical impact. Meanwhile, hormones like secretin and amylin appear to have complex and stage-dependent roles that warrant deeper investigation.
The faces high rates of obesity and T2DM, mirroring global trends. According to global health data, obesity has reached epidemic levels worldwide, driven by high-calorie diets and sedentary lifestyles. Many adults in Europe now live with overweight or obesity, increasing risks of diabetes, heart disease and other chronic conditions.
Understanding gut hormone dysregulation could help clinicians personalise treatment. It could also guide public health policy by clarifying which interventions are most effective. For example, drugs that target multiple gut peptides could become more widely recommended alongside lifestyle support.
This narrative review elevates the importance of gut hormones in managing obesity and T2DM. By showing just how deeply metabolic diseases intertwine with hormonal signalling, it paves the way for more precise treatments. The evidence suggests that future care will combine pharmaceutical, behavioural and possibly even peptide-based therapies to improve outcomes.
Sources:
- Tzeravini, E., Simati, S., Anastasiou, I. A., Dalamaga, M., & Kokkinos, A. (2026). Gut peptide alterations in type 2 diabetes and obesity: A narrative review. Current Obesity Reports. https://doi.org/10.1007/s13679-026-00687-7
- World Health Organization. (2024). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight (PubMed)
- Ng, M., Fleming, T., Robinson, M., et al. (2024). Obesity: prevalence, causes, consequences, management, preventive strategies and future research directions. Journal of Public Health. (PubMed)
