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Background: Adverse associations of low- and no-calorie sweetened beverages (LNCSB) with cardiometabolic outcomes in observational studies may be explained by reverse causality and residual confounding.Purpose: To address these limitations we used change analyses of repeated measures of intake and substitution analyses to synthesize the association of LNCSB with cardiometabolic outcomes.Data Sources: MEDLINE, Embase, and the Cochrane Library were searched up to 10 June 2021 for prospective cohort studies with ≥1 year of follow-up duration in adults.Study Selection: Outcomes included changes in clinical measures of adiposity, risk of overweight/obesity, metabolic syndrome, type 2 diabetes (T2D), cardiovascular disease, and total mortality.Data Extraction: Two independent reviewers extracted data, assessed study quality, and assessed certainty of evidence using GRADE. Data were pooled with a random-effects model and expressed as mean difference (MD) or risk ratio (RR) and 95% CI.Data Synthesis: A total of 14 cohorts (416,830 participants) met the eligibility criteria. Increase in LNCSB intake was associated with lower weight (5 cohorts, 130,020 participants; MD -0.008 kg/year [95% CI -0.014, -0.002]). Substitution of LNCSB for sugar-sweetened beverages (SSB) was associated with lower weight (three cohorts, 165,579 participants; MD, -0.12 [-0.14, -0.10,] kg/y) and lower incidence of obesity (OB) (one cohort, 15,765 participants; RR 0.88 [95% CI 0.88, 0.89]), coronary heart disease (six cohorts, 233,676 participants; 0.89 [0.81, 0.98]), cardiovascular disease mortality (one cohort, 118,363 participants; 0.95 [0.90, 0.99]), and total mortality (one cohort, 118,363 participants; 0.96 [0.94, 0.98]) with no adverse associations across other outcomes. Substitution of water for SSB showed lower weight (three cohorts, 165,579 participants; MD -0.10 kg/year [-0.13, -0.06]), lower waist circumference (one cohort, 173 participants; -2.71 cm/year [-4.27, -1.15]) and percent body fat (one cohort, 173 participants; -1.51% per year [-2.61, -0.42]), and lower incidence of OB (one cohort, 15,765 participants; RR 0.85 [0.75, 0.97]) and T2D (three cohorts, 281,855 participants; 0.96 [0.94, 0.98]). Substitution of LNCSB for water showed no adverse associations.Limitations: The evidence was low to very low certainty owing to downgrades for imprecision, indirectness, and/or inconsistency.Conclusions: LNCSB were not associated with cardiometabolic harm in analyses that model the exposure as change or substitutions. The available evidence provides some indication that LNCSB in their intended substitution for SSB may be associated with cardiometabolic benefit, comparable with the standard of care, water. [ABSTRACT FROM AUTHOR]

Background: Whether changes in consumption of sugary beverages or artificially sweetened beverages (ASBs) are associated with type 2 diabetes (T2D) risk has never been evaluated. Objective: We evaluated the association of changes in sugary beverage and ASB consumption over a 4-year period with subsequent 4-year risk of T2D among U.S. women and men. Methods: We followed-up 78,357 women in the Nurses' Health Study (1986-2012), 82,937 women in the Nurses' Health Study II (1991-2013) and 35,148 men in the Health Professionals Follow-up Study (1986-2012). Beverage intakes were assessed using validated food frequency questionnaires every 4 years. Cox proportional regression models were used to calculate hazard ratios (HRs) for T2D regarding 4-year changes in beverage consumption, adjusted for initial beverage intake and BMI. Results of the 3 cohorts were pooled using an inverse variance-weighted, fixed-effect meta-analysis. Results: During 2,849,389 person-years of follow-up, we documented 12,007 incident cases of T2D. Increasing sugary beverage intake by >0.5 serving/day over a 4-year period was associated with a 14% (95% CI: 7%, 21%) higher T2D risk compared with maintaining a stable consumption. Both beverages with added sugars (e.g., soft drinks) and 100% fruit juices were associated with higher T2D risk. Increasing ASB consumption by >0.5 serving/day was associated with a 19% (95% CI: 12%, 27%) higher T2D risk. Substituting ASB for sugary beverages was not associated with subsequent T2D risk (HR: 0.99, 95% CI: 0.96, 1.02). However, decreasing sugary beverage consumption and increasing water, coffee or tea intake by 1 serving/day was associated with a 3% to 11% lower risk of T2D. Conclusion: Increasing consumption of sugary beverages or ASBs was associated with a higher risk of T2D compared with maintaining a stable consumption of these beverages. Substituting water, coffee or tea but not ASB for sugary beverages was associated with lower T2D risk. Disclosure: J. Drouin-Chartier: Other Relationship; Self; Dairy Farmers of Canada. Y. Zheng: None. Y. Li: None. V. Malik: None. A. Pan: None. J.E. Manson: None. W.C. Willett: None. F. Hu: None. Funding: National Institutes of Health (UM1CA186107, UM1CA176726, UM1CA167552, DK112940, HL60712, HL118264); Canadian Institutes of Health Research (BPF-156628) [ABSTRACT FROM AUTHOR]