Long-Term Effect of Weight Regain Following Behavioral Weight Management Programs on Cardiometabolic Disease Incidence and Risk: Systematic Review and Meta-Analysis

Background: Behavioral weight management programs (BWMPs) enhance weight loss in the short term, but longer term cardiometabolic effects are uncertain as weight is commonly regained. We assessed the impact of weight regain after BWMPs on cardiovascular risk factors, diabetes, and cardiovascular disease. Methods: Trial registries, 11 databases, and forward-citation searching (latest search, December 19) were used to identify articles published in English, from any geographical region. Randomized trials of BWMPs in adults with overweight/obesity reporting cardiometabolic outcomes at ≥12 months at and after program end were included. Differences between more intensive interventions and comparator groups were synthesized using mixed-effects, meta-regression, and time-to-event models to assess the impact of weight regain on cardiovascular disease incidence and risk. Results: One hundred twenty-four trials reporting on ≥1 cardiometabolic outcomes with a median follow-up of 28 (range, 11–360) months after program end were included. Median baseline participant body mass index was 33 kg/m2; median age was 51 years. Eight and 15 study arms (7889 and 4202 participants, respectively) examined the incidence of cardiovascular disease and type 2 diabetes, respectively, with imprecise evidence of a lower incidence for at least 5 years. Weight regain in BWMPs relative to comparators reduced these differences. One and 5 years after program end, total cholesterol/HDL (high-density lipoprotein) ratio was 1.5 points lower at both times (82 studies; 19 003 participants), systolic blood pressure was 1.5 mm mercury and 0.4 mm lower (84 studies; 30 836 participants), and HbA1c (%) 0.38 lower at both times (94 studies; 28 083 participants). Of the included studies, 22% were judged at high risk of bias; removing these did not meaningfully change results. Conclusions: Despite weight regain, BWMPs reduce cardiometabolic risk factors with effects lasting at least 5 years after program end and dwindling with weight regain. Evidence that they reduce the incidence of cardiovascular disease or diabetes is less certain. Few studies followed participants for ≥5 years. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42018105744.

4 and in referenced protocol.

Search strategy
7 Present the full search strategies for all databases, registers and websites, including any filters and limits used.4 and in referenced protocol ( full search strategy for one database only) Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

4-5
Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

4-5
Data items 10a List and define all outcomes for which data were sought.Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

4-5
10b List and define all other variables for which data were sought (e.g.participant and intervention characteristics, funding sources).Describe any assumptions made about any missing or unclear information.
5, and in referenced protocol.

Study risk of bias assessment
11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

5
Effect measures 12 Specify for each outcome the effect measure(s) (e.g.risk ratio, mean difference) used in the synthesis or presentation of results.

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Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g.tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

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13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

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13c Describe any methods used to tabulate or visually display results of individual studies and syntheses.5-6

Item # Checklist item
Location where item is reported 13d Describe any methods used to synthesize results and provide a rationale for the choice(s).If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

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13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g.subgroup analysis, meta-regression).5-6 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results.

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Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).n/a Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome.n/a

Study selection 16a
Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram.

6
16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded.n/a

Study characteristics
17 Cite each included study and present its characteristics.

and supplemental material
Risk of bias in studies 18 Present assessments of risk of bias for each included study.6 and supplemental material

Results of individual studies
19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g.confidence/credible interval), ideally using structured tables or plots.

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Results of syntheses 20a For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies.6-10 and supplemental material 20b Present results of all statistical syntheses conducted.If meta-analysis was done, present for each the summary estimate and its precision (e.g.confidence/credible interval) and measures of statistical heterogeneity.If comparing groups, describe the direction of the effect.
6-10 and supplemental material 20c Present results of all investigations of possible causes of heterogeneity among study results.6-10 and supplemental material 20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results.6-10 and supplemental material Reporting biases 21 Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed.
assessments of certainty (or confidence) in the body of evidence for each outcome assessed.n/a DISCUSSION Discussion 23a Provide a general interpretation of the results in the context of other evidence.10-11 23b Discuss any limitations of the evidence included in the review.10-11