Data from more than 720,000 adults suggest that long-term consumption of artificial sweeteners may not be metabolically neutral, although researchers caution that the observational evidence remains of low certainty.

Study: The longitudinal association between artificial sweetener intake and the risk of type 2 diabetes among adults aged 18 years and older: a systematic review and meta-analysis. Image Credit: Anastassiya Bezhekeneva / Shutterstock
A recent meta-analysis published in the journal Frontiers in Nutrition suggests that higher intake of artificial sweeteners is associated with an increased risk of type 2 diabetes (T2D) among adults.
Based on the findings, clinicians and nutrition professionals should consider that artificial sweeteners may not be metabolically neutral or completely risk-free alternatives to sugar while developing nutritional strategies.
Health bodies should also consider the potential metabolic effects of artificial sweeteners when designing dietary policies and recommendations aimed at reducing excessive sugar and calorie intake to support long-term weight management and metabolic health.
The increasing prevalence of T2D worldwide and associated health and economic burden highlights an urgent need for strategies to reduce excessive sugar and overall energy intake.
Artificial sweeteners are frequently consumed in dairy products, processed foods, and beverages by people with excess body weight or metabolic conditions. This is because these sweeteners provide sweetness with little or no caloric content and are often used as a strategy to reduce overall energy intake and support weight or glycemic management.
While high sugar intake is known to increase T2D risk, there is ongoing debate about whether artificial sweetener intake could increase T2D risk in the long term.
While randomized controlled trials (RCTs) assessing short-term artificial sweetener intake have generally not detected significant adverse metabolic effects, prospective observational studies evaluating long-term intake have reported positive associations with T2D.
About the meta-analysis
In the present systematic review and meta-analysis, researchers investigated whether artificial sweetener consumption was longitudinally associated with the risk of T2D among adults.
The team included prospective observational and original population-based studies identified through Embase, PubMed, China National Knowledge Infrastructure (CNKI), and Web of Science from inception through March 2025. As part of data screening, they also manually screened the reference lists of the included studies to identify any additional relevant records. The team excluded commentaries, reviews, and conference abstracts from the review.
In the included studies, T2D was diagnosed using the World Health Organization (WHO) 1999 or American Diabetes Association (ADA) criteria. The team identified diabetic cases through participants’ self-reports and subsequently confirmed them using medical records, national registries, and clinically standardized criteria. Using food frequency questionnaires (FFQs), researchers assessed participants' artificial sweetener intake across all included studies.
Two researchers independently reviewed all relevant articles. After removing 12 duplicates, they initially screened titles and abstracts for 96 records, followed by full-text assessment of 34 articles. Disagreements were resolved by a third researcher.
The Newcastle–Ottawa Scale (NOS) helped the researchers evaluate study quality, with scores of seven or higher considered high quality. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, they determined the overall certainty of evidence in the included studies.
Random-effects models were used to calculate the pooled hazard ratios (HRs) for statistical analysis. The I2 statistic indicated heterogeneity between the studies. The researchers reanalyzed the results by sequentially excluding each study to assess the robustness of the findings and evaluated publication bias using Egger’s regression test and funnel plots.
Results and discussion
In total, the meta-analysis included six cohort studies with a mean follow-up of 10.1 years and 721,003 individuals from the United States (US), Japan, and Europe. The researchers drew on information from the NutriNet-Santé and EPIC-InterAct cohorts, the Multi-Ethnic Study of Atherosclerosis (MESA), the Japanese Public Health Center-based (JPHC) study, and the Health Professionals Follow-up Study (HPFS). The meta-analysis also included data from the Nurses’ Health Study (NHS) and NHS II. Based on NOS scores of 7-8, all the included records were of high quality.
During the follow-up period, there were 38,445 T2D cases, with a crude incidence of nearly 5.3 cases per 1,000 person-years. Compared with adults with low or no artificial sweetener intake, higher intake was associated with greater T2D risk (pooled HR, 1.31). Despite considerable heterogeneity across studies (I2 = 86%), there was no significant evidence of publication bias, and the sensitivity analysis yielded largely similar results.
Interestingly, heterogeneity between studies was reduced to about 69% when exposure variables were restricted to diet soda and artificially sweetened beverages, suggesting that differences in exposure definitions contributed substantially to the heterogeneity. The overall certainty of evidence, however, was graded as low, reflecting the observational evidence base, limited number of studies, and substantial between-study heterogeneity.
The authors discussed several proposed mechanisms that could potentially explain the observed association. Artificial sweeteners have been increasingly linked to changes in the composition and function of the gut microbiome. Such changes may disturb the balance of gut bacteria and affect insulin responsiveness, while also altering the integrity of the intestinal epithelial barrier.
The resulting changes in microbial activity and barrier function could promote inflammation and metabolic disturbances. Artificial sweeteners may also affect the neural and hormonal pathways that regulate appetite and energy balance.
Conclusion
The analysis found that higher intake of artificial sweeteners was associated with a greater risk of T2D. The findings raise questions about the long-term metabolic neutrality of artificial sweeteners when used as sugar substitutes. However, the results need to be viewed with caution.
All six studies were observational, and residual confounding, as well as preferential artificial sweetener use among people already at elevated metabolic risk, cannot be fully excluded. Exposure was also self-reported, introducing the possibility of recall bias.
The studies differed considerably in their populations, exposure definitions, intake categories, and covariate adjustment, contributing to significant heterogeneity and low certainty of evidence.
Journal reference:
- Lu, S., Lu, Y., Xu, R., Hou, W., Xu, T., & Tang, W. (2026). The longitudinal association between artificial sweetener intake and the risk of type 2 diabetes among adults aged 18 years and older: A systematic review and meta-analysis. Frontiers in Nutrition, 13, 1886458. DOI: 10.3389/fnut.2026.1886458, https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2026.1886458/full