Allulose, a rare low-calorie sugar, has attracted interest for its potential metabolic benefits, particularly amongst individuals managing diabetes or taking glucagon-like peptide-1 (GLP-1) receptor agonist medications. Whilst preliminary research suggests allulose may modestly influence blood glucose levels and possibly stimulate endogenous GLP-1 secretion, the evidence remains limited and largely derived from animal studies. This article examines the current understanding of allulose's effects on GLP-1 activity, explores potential metabolic benefits, and provides practical guidance for patients considering allulose alongside GLP-1-based therapies. Understanding the science and safety considerations is essential for informed decision-making.

What Is Allulose and How Does It Work in the Body?

Allulose, also known as D-psicose, is a rare sugar that occurs naturally in small quantities in foods such as wheat, figs, and raisins. Structurally, it is classified as a monosaccharide and is considered an epimer of fructose, meaning it shares the same molecular formula but differs in the spatial arrangement of atoms. Despite its sweet taste—approximately 70% as sweet as sucrose—allulose provides minimal calories, typically around 0.2–0.4 kilocalories per gram compared to the 4 kilocalories per gram found in regular sugar.

The unique metabolic profile of allulose differs from conventional sugars. Approximately 70% of an oral dose is absorbed in the small intestine, minimally metabolised, and excreted unchanged in urine within 24 hours; the remainder reaches the colon and may be fermented or excreted in faeces. Importantly, allulose does not meaningfully raise blood glucose or insulin levels, making it an attractive option for individuals managing diabetes or seeking to reduce caloric intake.

Allulose has gained attention in recent years as a low-calorie sweetener and potential functional food ingredient. In Great Britain, novel food regulations are overseen by the Food Standards Agency (FSA), while Northern Ireland may follow EU rules. Manufacturers must comply with safety assessments before marketing products containing allulose. The mechanism by which allulose exerts its effects involves minimal impact on glycaemic response, which has prompted research into its potential metabolic benefits.

Key characteristics of allulose include:

• Minimal caloric contribution

• Does not meaningfully raise blood glucose or insulin levels

• Substantial absorption with urinary excretion of unchanged allulose

• Natural occurrence in select foods

Understanding these fundamental properties is essential when considering allulose's potential interactions with metabolic pathways, including those involving incretin hormones such as glucagon-like peptide-1 (GLP-1).

Understanding GLP-1 and Its Role in Blood Sugar Control

Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted primarily by enteroendocrine L-cells located in the distal small intestine and colon. This hormone plays a crucial role in glucose homeostasis through multiple mechanisms. Following food intake, GLP-1 is released into the bloodstream, where it stimulates glucose-dependent insulin secretion from pancreatic beta cells, suppresses glucagon release from alpha cells, and slows gastric emptying. These coordinated actions help to regulate postprandial blood glucose levels effectively.

The physiological importance of GLP-1 extends beyond glucose control. The hormone also influences satiety signals in the central nervous system, contributing to reduced appetite and food intake. This multifaceted action has made GLP-1 receptor agonists—medications that mimic the effects of endogenous GLP-1—valuable therapeutic agents for managing type 2 diabetes and, more recently, obesity. Examples of GLP-1 receptor agonists licensed in the UK include semaglutide, dulaglutide, liraglutide, exenatide and lixisenatide.

Endogenous GLP-1 has a very short half-life, typically 1–2 minutes, as it is rapidly degraded by the enzyme dipeptidyl peptidase-4 (DPP-4). This rapid degradation necessitates the development of modified GLP-1 analogues or DPP-4 inhibitors to achieve sustained therapeutic effects. The National Institute for Health and Care Excellence (NICE) provides guidance on the use of GLP-1 receptor agonists in guideline NG28, recommending them for type 2 diabetes in specific contexts, such as when other therapies have proven inadequate, particularly in people with higher BMI or cardiovascular risk factors.

GLP-1's primary functions include:

• Enhancing insulin secretion in response to glucose

• Suppressing inappropriate glucagon release

• Delaying gastric emptying

• Promoting satiety and reducing appetite

Understanding GLP-1's role is fundamental when evaluating whether dietary interventions, such as allulose consumption, might influence incretin hormone activity or complement GLP-1-based therapies.

Potential Benefits of Allulose for Metabolic Health

Emerging research has investigated whether allulose consumption might offer metabolic benefits, particularly regarding glucose regulation and incretin hormone secretion. Several animal studies and preliminary human trials have suggested that allulose may influence postprandial glucose responses and potentially affect GLP-1 secretion, though the evidence base remains limited and requires further validation.

A small number of human studies have examined allulose's effects on glucose metabolism. Some research indicates that consuming allulose (typically 5-10g with meals) alongside carbohydrate-containing meals may modestly attenuate postprandial blood glucose excursions. The proposed mechanisms include inhibition of disaccharidase enzymes in the small intestine, which may slow the breakdown and absorption of other sugars, and potential stimulation of GLP-1 secretion from intestinal L-cells. However, it is important to note that these findings are preliminary, many are based on animal or in vitro studies, and there is no official link established between allulose consumption and clinically significant enhancement of GLP-1 activity in humans.

Animal studies have provided some mechanistic insights. Research in rodent models suggests that allulose may increase GLP-1 secretion, possibly through effects on intestinal glucose transporters or direct stimulation of enteroendocrine cells. Additionally, some studies have reported improvements in insulin sensitivity and reductions in fat accumulation with chronic allulose consumption. Nevertheless, translating these findings to human populations requires caution, as metabolic responses can differ substantially between species.

For individuals taking GLP-1 receptor agonist medications, as of 2025, no controlled human studies assessing allulose with GLP-1 receptor agonists have been identified. There is currently insufficient evidence to determine whether allulose consumption provides additive benefits or interferes with medication efficacy.

Potential metabolic effects of allulose (requiring further research):

• Modest reduction in postprandial glucose levels

• Possible stimulation of endogenous GLP-1 secretion

• Potential improvement in insulin sensitivity

• Reduction in overall caloric intake when substituted for sugar

Patients should discuss any dietary modifications with their healthcare provider, particularly when managing diabetes or taking glucose-lowering medications.

Safety Considerations When Using Allulose

Allulose is generally recognised as well-tolerated when consumed in moderate amounts, though several safety considerations warrant attention. The primary adverse effects reported in clinical studies relate to gastrointestinal symptoms, which occur because a portion of ingested allulose reaches the large intestine. Common symptoms include bloating, abdominal discomfort, loose stools, and diarrhoea, particularly when consumed in quantities exceeding 0.4–0.5 grams per kilogram of body weight per day as a total daily intake.

The gastrointestinal effects of allulose are dose-dependent and vary considerably between individuals. Some people may tolerate larger amounts without difficulty, whilst others experience symptoms at lower doses. These effects are similar to those observed with other poorly absorbed carbohydrates, such as sugar alcohols (polyols). Gradual introduction of allulose into the diet may help minimise gastrointestinal discomfort as the gut microbiome adapts.

In Great Britain, allulose is subject to novel food regulations overseen by the Food Standards Agency (FSA). Manufacturers seeking to market products containing allulose must obtain authorisation demonstrating safety for human consumption. Safety assessments have concluded that allulose is safe for the general population when used as intended, though specific authorisations may vary. Consumers should verify that products comply with UK food safety standards.

Important safety considerations include:

• Gastrointestinal symptoms at higher doses

• Individual tolerance variability

• Potential for hypoglycaemia when combined with insulin or sulphonylureas

• Limited long-term safety data in humans

• Limited data in children and adolescents

Patients with diabetes taking glucose-lowering medications should exercise caution when introducing allulose. The hypoglycaemia risk is primarily with insulin or sulphonylureas, as GLP-1 receptor agonists alone rarely cause hypoglycaemia. However, substituting allulose for sugar whilst maintaining medication doses could theoretically increase hypoglycaemia risk. Blood glucose monitoring should be maintained, and any concerning symptoms—such as dizziness, confusion, sweating, or palpitations—should prompt immediate contact with a healthcare professional. Pregnant or breastfeeding women should consult their GP or midwife before using allulose, as safety data in these populations are limited.

Patients should report any suspected side effects from medicines to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

Practical Guidance on Allulose and GLP-1 Medications

For individuals considering allulose as part of their dietary strategy, particularly those taking GLP-1 receptor agonist medications, several practical considerations can help ensure safe and effective use. Firstly, it is essential to recognise that allulose should not be viewed as a replacement for prescribed medications or established dietary advice. Any changes to diet or medication regimens should be discussed with a GP, diabetes specialist nurse, or registered dietitian.

When introducing allulose, start with small amounts—typically 5–10 grams per day—and gradually increase as tolerated. This approach helps identify individual tolerance thresholds and minimises gastrointestinal side effects. Be aware that allulose may exacerbate GLP-1 receptor agonist-related gastrointestinal symptoms; consider slower titration or dose reduction of allulose if symptomatic. Allulose can be used in beverages, baking, or as a tabletop sweetener, though its properties differ slightly from sucrose in cooking applications. Reading product labels carefully is important, as some commercial products may contain allulose blended with other sweeteners.

For patients taking GLP-1 receptor agonists such as semaglutide or dulaglutide, there is currently no evidence suggesting that allulose interferes with medication efficacy or causes adverse interactions. However, the combination has not been systematically studied. Patients should continue their prescribed medication regimen and maintain regular blood glucose monitoring as advised by their healthcare team. If using allulose to reduce overall sugar intake, this dietary modification may contribute to improved glycaemic control, but medication adjustments should only be made under medical supervision.

Practical recommendations include:

• Discuss dietary changes with your healthcare provider before starting allulose

• Begin with small doses and increase gradually

• Monitor blood glucose levels regularly, especially if taking insulin or sulphonylureas

• Be aware of gastrointestinal symptoms and adjust intake accordingly

• Do not discontinue or alter prescribed medications without medical advice

When to contact your GP:

• Experiencing hypoglycaemia (blood glucose <4 mmol/L)

• Persistent gastrointestinal symptoms affecting quality of life

• Uncertainty about medication interactions

• Difficulty achieving glycaemic targets despite dietary modifications

NICE guidance (NG28) emphasises individualised diabetes management, incorporating dietary modification, physical activity, and appropriate pharmacotherapy. Allulose may serve as one component of a broader dietary strategy, but it should complement—not replace—evidence-based treatments. Regular review with healthcare professionals ensures that any dietary interventions align with overall treatment goals and do not compromise safety or efficacy of prescribed therapies.

Frequently Asked Questions