Non-nutritive Sweeteners for Diabetes Mellitus

Author(s): Lohner S, Kuellenberg de Gaudry D, Toews I, Ferenci T, Meerpohl JJ
Publication name: Cochrane Database of Systematic Reviews 2020 May 25;5:CD012885. doi: 10.1002/14651858.CD012885.pub2
Publication year: 2020


Background: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown.
Objectives: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus.
Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions.
Selection criteria: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups.
Data collection and analysis: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane ‘Risk of bias’ tool and the certainty of evidence using the GRADE approach.
Main results: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all ’Risk of bias’ domains; most of the included trials did not report the method of randomisation.
Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events.
Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence).
One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events.
The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects.
Authors’ conclusions: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.


The present systematic review by Lohner et al, supported by the World Health Organization (WHO), found no adverse effect on glycaemic control or on any other health outcome from the consumption of low/no calorie sweeteners in people with diabetes. However, the authors assess the available evidence as of very low quality and therefore conclude that there is inconclusive evidence regarding the effects of sweeteners’ consumption on clinically relevant benefit or harm for diabetes.

However, this work did not assess the evidence indicating the significant benefit of low/no calorie sweeteners compared with caloric sweeteners such as sugar on post-prandial (i.e. after-eating) blood glucose levels. The literature of published clinical studies exploring the short-term benefit of low/no calorie sweeteners on blood glucose levels post-prandially, when used instead of sugars, represent the vast majority of randomised controlled trials looking into effects of sweeteners on glycaemia. By excluding the wealth of clinical studies investigating the acute effect of low/no calorie sweeteners on blood glucose levels, this study by Lohner et al cannot provide a thorough evaluation of the beneficial role of low/no calorie sweeteners in diabetes. Also, a methodological limitation of this study is the lack of subgroup analysis by type of sweetener or by type of diabetes.

Compared to sugar or other carbohydrates, low/no calorie sweeteners cause a lower rise in blood glucose levels post-prandially. This assertion is supported by comprehensive systematic reviews of the literature as well as by the European Food Safety Authority (EFSA), which concluded in a scientific opinion that: “Consumption of foods containing intense sweeteners instead of sugar induces a lower blood glucose rise after their consumption compared to sugar-containing foods”. This is an authorised health claim in the EU as stated in the Commission Regulation (EU) N°432/2012.

A critical appraisal of the review by Lohner et al. is available on the ISA website by clicking here.

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