Metabolic effects of GLP-1 and GLP-2 across fed, fasting, and starvation states: A systematic review with structured narrative synthesis
Aime Patrick Niyomugabo, Leopold Ntakirutimana, Pelagie Izabayo, Clenie Isingizwe, Olufunke Onaadepo, Abdullateef Isiaka AlagbonsiBackground
GLP-1 and GLP-2 are co-secreted gut-derived peptides that regulate glucose homeostasis, appetite, nutrient handling, and intestinal adaptation. Their physiological effects vary across nutritional states, with evidence strongest for the fed (postprandial) state and remaining limited for prolonged fasting and starvation.
Objective
This study systematically evaluated and compared the metabolic effects of endogenous and experimentally manipulated GLP-1 and GLP-2 across fed, fasting, and starvation conditions, while distinguishing human clinical evidence from animal and mechanistic studies.
Design
This systematic review was reported in accordance with the PRISMA 2020 guidelines, using a structured narrative synthesis.
Data Sources and Methods
PubMed/MEDLINE, Scopus, Wiley Online Library, and African Journals Online were searched for primary human, animal, and relevant in vitro studies published from January 1, 1990 through December 31, 2025. Thirty-six studies met the inclusion criteria and were included in the review. Evidence was stratified by hormone, nutritional state, model, exposure type, and outcome domain. Risk of bias was assessed using design-appropriate tools.
Results
Most studies focused on the fed state. GLP-1 primarily improves postprandial glucose regulation and satiety, whereas GLP-2 promotes intestinal growth, nutrient absorption, and lipid metabolism. Evidence during prolonged fasting or starvation was limited and largely derived from animal studies, suggesting possible adaptive roles in maintaining metabolic homeostasis.
Conclusion
GLP-1 and GLP-2 play complementary roles in regulating glucose homeostasis, energy balance, and intestinal function, with the strongest evidence supporting their actions in the fed state. Although they are promising therapeutic targets for metabolic and gastrointestinal disorders, further standardized human studies are needed to clarify their roles during prolonged fasting and starvation.