G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Clinical trials have shown that GLP1Ra-based therapy produces substantial weight loss, including 12-15% over one year with semaglutide and weight reductions with tirzepatide comparable to bariatric surgery.

“Indeed, clinical trials demonstrate substantial weight loss achievable with GLP1Ra-based therapy, ranging from 12-15% over a one-year period for semaglutide (6), to weight losses rivaling what is seen with bariatric surgery for tirzepatide (7).”

• cites [6] sourcePartly supported

  The Change in Body Weight section reports 14.9% mean weight loss with semaglutide, within the cited 12–15% range. That result was measured at week 68, not over one year. The tirzepatide comparison is attached to a different citation and is not judged here. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [7] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The meta-analysis was conducted in accordance with PRISMA guidelines.

“This meta-analysis followed the Preferred Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (14).”

• cites [14] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Preclinical studies suggest that GLP1Ra-based therapies may improve bone health by promoting bone formation and reducing bone turnover.

“Interestingly, pre-clinical studies suggest that GLP1Ra-based therapies may positively impact bone health by promoting bone formation and reducing bone turnover; yet, currently available clinical data on effects of GLP1Ras on human bone metabolism are largely neutral (i.e., no consistent changes are observed in bone turnover biomarkers, bone mineral density (BMD), or fracture risk (12)).”

• cites [12] sourcePartly supported

  The Results (3.2, Animal Studies; page not provided) report increased bone formation and decreased bone resorption in treated rats, supporting the proposed preclinical benefit. But the Discussion says most animal studies showed increased bone turnover markers, so the claim that treatment reduces bone turnover is not supported; reduced resorption is more precise. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

The clinical consequences of muscle and bone loss include incident fracture, disability, and death.

“where the clinical consequences of muscle and bone loss (including incident fracture, disability, and even death) are well described (9).”

• cites [9] sourcePartly supported

  The Epidemiological studies section (p. 4) links weight loss with increased fracture risk, while the Body composition section (p. 7) connects muscle mass with physical performance and fall prevention. The paper does not describe disability or death as consequences of muscle and bone loss; its Introduction (p. 3) discusses mortality in relation to weight loss, with a qualification about randomized trials. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

The obesity epidemic continues to negatively affect health in the United States.

“The epidemic of obesity continues to negatively impact health in the United States (1, 2).”

• cites [1]Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [2] sourcePartly supported

  The Clinical context and Conclusions sections say the obesity epidemic continues and that obesity causes substantial morbidity and increased mortality. The Liver section links obesity to a common cause of chronic liver disease in the United States, but the paper does not specifically establish the claim about the epidemic’s overall health impact in the United States. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

A 2019 review reported that 20-50% of total weight lost with GLP1Ra-based therapies is lean mass.

“A 2019 review, which summarizes the effects obesity of GLP1Ra-based therapies on body composition (predominantly assessed via dual energy x-ray absorptiometry, or DXA) reports that 20-50% of total lost weight is attributed to lean mass (LM), warranting attention and potential intervention (10).”

• cites [10] sourcePartly supported

  The Conclusions report that lean body mass or fat-free mass accounted for 20–50% of weight lost in 27 of 43 assessable groups, but those groups included GLP-1 receptor agonist, SGLT2 inhibitor, and combination therapies. The Results section gives several GLP-1 receptor agonist examples in that range, alongside results outside it. The figure is therefore supported as a common finding, not as a general proportion for all GLP-1 receptor agonist treatment. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

Study quality was evaluated with the revised Cochrane risk-of-bias tool for randomized trials, covering five domains.

“The revised Cochrane risk-of-bias tool for randomized trials was used to assess the quality of included studies according to the following five domains (D): D1 – Bias arising from the randomization process; D2 – Bias due to deviations from intended intervention; D3 – Bias due to missing outcome data; D4 – Bias in measurement of the outcome; D5 – Bias in selection of the reported result.”

• cites [15] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Two articles reported lean mass results for a subset rather than the full parent-trial sample.

“with two articles presenting LM outcomes in only a subset of participants from the parent trial (6, 7).”

• cites [6] sourceSupported
• cites [7] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Functional improvements after lifestyle or surgical weight loss are often attributed to fat-loss-associated improvements in muscle quality.

“Functional improvements following lifestyle or surgical weight loss are often attributed to fat-loss associated improvements in muscle quality (38, 39).”

• cites [38] sourceNot checked — no full text of the source
• cites [39] sourcePartly supported

  The Discussion (page unavailable) reports that fat-mass loss predicts improved gait speed and mobility in older adults and identifies muscle quality, rather than muscle quantity, as important to physical performance. It does not establish that improved muscle quality mediates the gains after fat loss, and the studies analyzed did not examine surgical weight loss. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Only two trials reporting BMD outcomes met the inclusion criteria, preventing formal data analysis.

“Only two trials reporting BMD outcomes fit our inclusion criteria ((23, 24); see Table 1), prohibiting formal data analysis; however, they are descriptively summarized here.”

• Also stated in: § Discussion · plain

  “It was unexpected that only two studies meeting our inclusion criteria would be identified that reported on change in DXA-acquired BMD (23, 24), with one showing no change in whole body BMD, despite significant weight loss (24), and the other suggesting increased spine (but not total hip or femoral neck) BMD (23).”

• cites [23] sourceSupported
• cites [24] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Recent data suggest that half of individuals living with obesity will stop taking GLP1Ra medications one year after starting treatment.

“Indeed, recent data on the prevalence of GLP1Ra discontinuation suggest half of individuals living with obesity will stop taking these medications one year following initiation of treatment (54).”

• cites [54] sourcePartly supported

  Table 1 (Results; page not provided) reports 50.3% discontinuation at the 12-month assessment among new users with obesity only. The figure was 34.2% among those with both obesity and type 2 diabetes, so the claim overgeneralizes the roughly half figure to all individuals living with obesity. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

In the Eriksson et al. trial, lumbar spine BMD was higher after exenatide treatment (1.24±0.19 g/cm2) than after placebo (1.12±0.16 g/cm2), with p=0.02.

“Post-intervention, similar and modest weight loss was observed in both groups (i.e. ~2.3 kg; 2% of baseline weight), with higher lumbar spine BMD reported after exenatide treatment (1.24±0.19 g/cm2) as compared to placebo (1.12±0.16 g/cm2); p=0.02.”

• cites [23] sourcePartly supported

  The Results (Effect of Exenatide on Biomarkers of Bone Turnover and Bone Mineral Density; page unavailable) report higher L2–L4 BMD after exenatide and lower BMD after placebo, with a significant time-by-group interaction (p = 0.016, approximately 0.02 when rounded). The passages in our copy do not provide the claimed post-treatment values of 1.24 ± 0.19 and 1.12 ± 0.16 g/cm²; they also identify the p-value as a time-by-group interaction, not a post-treatment between-group comparison. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Weiss et al., despite similar absolute weight loss of about 7%, the percentage of weight lost as lean mass was greatest with caloric restriction alone, lower when exercise was added, and virtually absent with exercise alone.

“Despite achieving similar absolute weight loss (~7% of baseline weight) the percentage of weight lost as LM was greatest in the caloric restriction group (2% of baseline LM, 18% of total weight lost), less when exercise was added to caloric restriction (1% of baseline LM; 6% of total weight lost), and virtually non-existent in the exercise only group (<1% of baseline LM; 2% of total weight lost).”

• cites [26] sourcePartly supported

  The Results (page unavailable) report about 7% weight loss in all three groups, with whole-body lean-mass loss of about 2% under caloric restriction, about 1% with restriction plus exercise, and no detected loss with exercise alone. These findings support the claimed ordering, but the passages do not report the cited proportions of total weight lost as lean mass (18%, 6%, and 2%). (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

Some long-term data from lifestyle-based weight loss interventions suggest that lean mass and BMD may not be recovered with weight regain.

“As some long-term data from lifestyle-based weight loss interventions suggest LM (58) and BMD (59, 60) may not be recovered with weight regain, better understanding of the effects of intermittent use of GLP1Ra-based therapies on long-term change in body composition represents another important area of further inquiry.”

• cites [58] sourceNot checked — no full text of the source
• cites [59] sourceSupported
• cites [60] sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Relying on Covidence machine learning and automation features carries a limitation of possibly missing duplicates and references considered not to report on RCTs.

“Second, although Covidence machine learning and automation features have been reviewed as having a very low and acceptable risk of missing duplicates and references considered as not reporting on RCTs (61), we acknowledge the limitation of relying on those features.”

• cites [61] sourcePartly supported

  The Results (page not available) report that the Cochrane RCT Classifier missed 224 of 44,007 studies with sufficient information for machine classification; the Discussion calls that risk acceptable when records with insufficient information are checked manually. The paper evaluates Cochrane’s classifier, not Covidence’s features, and does not establish a risk of missing duplicates. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In a 2017 study by Weiss et al., 50 middle-aged adults were randomized to achieve 6-8% weight loss over four months through caloric restriction, exercise, or their combination.

“To illustrate, a 2017 publication by Weiss et al. (26), randomized 50 middle-aged adults to achieve 6-8% weight loss over a four-month period via caloric restriction, exercise, or their combination.”

• cites [26] sourcePartly supported

  The Abstract Methods describe adults aged 45–65 assigned to a 6–8% weight-loss goal through calorie restriction, exercise, or both, with measurements about 17 weeks apart. However, Results > Participants says 69 participants were randomly allocated and 52 completed the study and complied with the interventions; it does not support the claim that 50 were randomized. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing).

In the Eriksson et al. trial, both groups had similar and modest weight loss of about 2.3 kg, or 2% of baseline weight.

“Post-intervention, similar and modest weight loss was observed in both groups (i.e. ~2.3 kg; 2% of baseline weight), with higher lumbar spine BMD reported after exenatide treatment (1.24±0.19 g/cm2) as compared to placebo (1.12±0.16 g/cm2); p=0.02.”

• cites [23] sourceSupported

May combine two claims.

In the Eriksson et al. trial, 45 patients with schizophrenia and obesity were randomized to 2.0 mg once-weekly exenatide or placebo, with total hip, femoral neck, and lumbar spine BMD measured at baseline and three months.

“In the three-month trial conducted by Eriksson and colleagues (23), 45 patients living with schizophrenia and obesity were randomized to 2.0 mg once-weekly exenatide or placebo with total hip, femoral neck, and lumbar spine BMD measured at baseline and three months.”

• cites [23] sourceSupported

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

There is likely a threshold at which lean mass loss becomes problematic, and this threshold may vary by individual.

“However, clinical concern remains that there is likely a threshold at which LM loss becomes problematic, which may vary by individual (40).”

• cites [40] sourceCould not verify

  The Introduction (page unavailable) describes individual variation in physical-function responses to weight loss, including null or negative responses. It does not address whether lean-mass loss becomes problematic above a threshold or whether that threshold varies by individual. Searches for lean mass, fat-free mass, and a harmful-loss threshold found no passage establishing the claim. (LLM, conf=0.73)

  Experimental — accuracy not yet measured

May combine two claims.

The same meta-analysis that reported nearly a quarter lean mass loss after bariatric surgery also reported preservation of muscle strength.

“Indeed, the same meta-analysis reporting nearly a quarter lean mass loss secondary to bariatric surgery also reported preservation in muscle strength (28).”

• cites [28] sourcePartly supported

  The Results section reports a 7.4 kg reduction in lean mass and no statistically significant change in handgrip strength after bariatric metabolic surgery. It does not report a loss of nearly a quarter of baseline lean mass. Its figures imply that lean mass accounted for approximately a quarter of the combined lean- and fat-mass loss, but that is a different measure. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Higher dietary protein during weight loss attenuates total lean mass losses; middle-aged and older adults consuming more than 1.0 g/kg/day retain more lean mass than those on normal protein diets.

“As with exercise, higher levels of dietary protein during weight loss also attenuate total LM losses, with meta-analytic data showing that middle-aged and older adults (i.e. 50+ years) who consume higher levels of dietary protein (>1.0 g/kg/d) during weight loss retain more lean mass in comparison with those following normal protein diets (~21% vs ≥30% of total weight lost as LM) (27).”

• cites [27] sourcePartly supported

  The Results and Discussion (p. 8) support the main claim: adults aged 50 and older on higher-protein diets retained more lean mass during weight loss than those on normal-protein diets. But the parenthetical misreads the percentages. The Results (p. 8) report that 21% of higher-protein groups, versus 50% of normal-protein groups, lost at least 30% of body mass as lean mass; they do not report average lean-mass losses of about 21% versus at least 30%. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In Mok et al., total body BMD was unchanged, with an adjusted mean difference of -0.00 g/cm2 (95% CI -0.02 to 0.02).

“From baseline to six months, a greater reduction in body weight was observed in the 3.0 mg liraglutide group compared with the placebo group (adjusted mean difference: −9.16 kg (95% CI, −11.45 to −6.87), yet total body BMD was unchanged (adjusted mean difference: −0.00 g/cm2 (95% CI, −0.02 to 0.02).”

• cites [24] sourcePartly supported

  Table 2 in the Results reports an adjusted bone-density difference of −0.00 (95% CI, −0.02 to 0.02), supporting the claim of no detected difference between groups. However, our copy labels the unit g/m², not the claim’s g/cm². (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

Funnel plots showed a high degree of heterogeneity across articles, but the bidirectional standard errors did not suggest strong publication bias.

“All plots demonstrated a high degree of heterogeneity across articles (as reflected in the wide dispersion of points); however, given the bidirectionality of the standard errors, there does not appear to be strong indication of publication bias.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

At baseline, participants in the lean mass trials had a mean age of 41.7 years (SD 7.6) and 75% were female.

“At baseline, participants were 41.7±7.6 years of age and 75% female, with BMIs ranging from 30-43 kg/m2.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The included trials were published between 2017 and 2023, spanning six years.

“Trials were published over a six-year period (2017-2023) and reported on LM outcomes in a total of 659 participants (GLP1Ra-based therapies: n=419; placebo: n=240).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Target populations varied: two trials enrolled participants with type 1 diabetes, two with polycystic ovary syndrome, one with schizophrenia, and one following gastric bypass with poor weight loss.

“Target populations varied widely, with two trials specifically enrolling participants with type 1 diabetes mellitus (19, 20), two with polycystic ovary syndrome (17, 21), one with schizophrenia (22), and one following gastric bypass resulting in poor weight loss (24).”

Probably not a substantial claim: may not pass S3 (load-bearing).

Seven of the included trials reported total body lean mass outcomes.

“with seven reporting on change in total body LM and two reporting on change in BMD.”

May combine two claims.

Five included articles were judged to have low risk of bias in all domains, and four were judged to have some concerns.

“Briefly, five articles were judged as having a low risk of bias in every domain (6, 7, 18, 20, 22), and four articles were judged to have some concerns (17, 19, 21, 24), attributed to potential bias arising from the randomization process (17), from deviations from intended intervention (19, 21), due to missing outcome data (17, 19), and from measurement of the outcome (21, 24).”

Probably not a substantial claim: may not pass S3 (load-bearing).

The literature search across PubMed and Web of Science returned 2,618 articles.

“A total of 2,618 articles were selected through the implementation of search strategies in PubMed and Web of Science.”

May combine two claims.

Lean mass loss in the GLP1Ra group accounted for 30.8% of total mass lost, or approximately 30% of total weight lost.

“Lean mass loss in the GLP1Ra group constituted 30.8% of total mass lost.”

• Also stated in: § Discussion · plain

  “First, total body LM loss comprises approximately 30% of total weight lost with GLP1Ra-based therapy.”

• Also stated in: § Discussion · plain

  “In conclusion, results from this meta-analysis focused on DXA-acquired outcomes show approximately 30% of total weight lost achieved with GLP1Ra-based treatment is attributed to LM.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The average number of participants per study was 73, with a range of 35 to 160.

“An average of 73 participants/study (range: 35-160) was reported, with two articles presenting LM outcomes in only a subset of participants from the parent trial (6, 7).”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Follow-up duration in the lean mass trials ranged from 12 to 72 weeks, with a mean of 33.5 weeks.

“with follow up times ranging from 12-72 (mean: 33.5) weeks.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Baseline body mass index in the lean mass trials ranged from 30 to 43 kg/m2.

“with BMIs ranging from 30-43 kg/m2.”

Probably not a substantial claim: may not pass S3 (load-bearing).

There was a surprising lack of published data quantifying the effect of GLP1Ra-based therapy on BMD outcomes.

“Second, there was a surprising lack of published data quantifying the effect of GLP1Ra-based therapy on BMD outcomes.”

May combine two claims.

Weight loss was derived mainly from fat mass, with a treatment effect difference of -4.6 kg (95% interval -7.6 to -1.6).

“Loss was derived mainly from FM (treatment effect difference: −4.6 kg (−7.6, −1.6)).”

May combine two claims.

No posterior credible interval indicated a significant difference in weight or body composition by treatment indication, including no significantly increased lean mass loss when GLP1RAs were prescribed at chronic weight management doses.

“None of the posterior credible intervals indicated significant differences in weight or composition by treatment indication.”

• Also stated in: § Discussion · plain

  “Secondary analyses stratifying treatment effects by indication do not show statistically significantly increased LM loss when GLP1Ras are prescribed at doses indicated for chronic weight management.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A sensitivity analysis tested whether findings held when one study's outlying variability estimate was potentially misspecified.

“A sensitivity analysis was performed to ensure the robustness of the results to the possible misspecification of one study’s outlying variability estimate.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Each review phase required two affirmative votes for a study to proceed.

“Two “yes” votes were required per study in each review phase.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Data extraction was performed by two independent extractors, with a third reviewer resolving conflicts and providing consensus.

“Data extraction from relevant studies was facilitated by Microsoft Excel spreadsheet tools and two independent extractors (KMB, TC), with a third reviewer (MCS) enlisted to resolve conflicts and provide consensus, when required.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A more recent review of obesity pharmacotherapy concluded that the percentage of muscle mass lost relative to fat mass was non-significant.

“In contrast, a more recent review evaluating the effects of obesity pharmacotherapy (including newer incretin-memetics) on body composition concludes that a non-significant percentage of muscle mass is lost, relative to fat mass (11).”

• cites [11] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The analyses were considered exploratory because no confirmatory a priori power calculations were performed.

“Statistical comparisons were deemed significant when the 95% CI excluded the null mean difference of zero; however, all analyses are considered exploratory due to the absence of confirmatory a priori power calculations.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Two reviewers independently assessed the included studies for risk of bias.

“Two reviewers (LD, FSM) assessed included studies independently.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Five reviewers independently screened titles and abstracts of relevant citations.

“First, five reviewers (KMB, TC, LD, FSM, and MCS) independently screened titles and abstracts of relevant citations.”

May combine two claims.

The observed proportion of lean mass loss with GLP1Ra-based therapy is on the higher end of what might be expected from lifestyle-based weight loss and more closely resembles what is seen with bariatric surgery.

“Overall, this proportion is on the higher end of what might be expected with lifestyle-based weight loss and more closely aligns with what is seen with bariatric surgery.”

May combine two claims.

Bariatric surgery is typically associated with a greater rate and degree of total weight loss than lifestyle-based weight loss, which increases the potential for lean mass loss.

“In contrast to lifestyle-based weight loss, bariatric surgery is typically associated with a greater rate and degree of total weight loss, both of which augment the proportion of weight loss-associated LM loss; thus, the potential for LM loss is higher.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Exclusive use of PubMed and Web of Science databases may have omitted relevant studies.

“First, the exclusive use of PubMed and Web of Science databases may have omitted relevant studies.”

Classified as probably not a substantial claim.

The GLP1Ra-based therapy intervention category collapsed across several medications with differing indications, dosing regimens, and effectiveness on weight loss outcomes.

“Moreover, the “GLP1Ra-based therapy” intervention category collapsed across several medications with differing indications, dosing regimens, and effectiveness on weight loss outcomes.”

• AssumptionRests on an assumption: The various GLP1Ra-based therapies included in the meta-analysis are sufficiently similar to be pooled into a single intervention category.

Probably not a substantial claim: may not pass S3 (load-bearing).

The amount of lean mass lost during weight loss varies widely depending on factors including the rate of weight loss, the degree of energy and nutrient deficit, the mode of weight loss, and whether exercise is included.

“The amount of LM lost during weight loss is known to vary widely depending on several factors, including the rate at which weight is lost and degree of energy and nutrient deficit, both of which can be influenced by the mode of weight loss, and whether exercise is incorporated into the weight loss prescription (25).”

• cites [25] sourceNot checked — no full text of the source

May combine two claims.

The relatively short study durations of 3-6 months and the lack of sensitivity of whole body BMD to change could also explain the BMD findings.

“However, the relatively short study durations (i.e. 3-6 months; bone remodeling typically takes a minimum of six months (45)) and lack of sensitivity in whole body BMD to change could also explain these findings.”

• cites [45] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

A certain degree of lean mass loss with weight loss is expected and may be adaptive; determining whether it is maladaptive requires evidence of negative effects on health outcomes.

“A certain degree of LM loss with weight loss is expected, even adaptive; thus, determining whether the loss is maladaptive requires evidence of negative impact(s) on health outcomes.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The Covidence systematic review software platform was used to reduce reviewer error and bias during screening and data extraction.

“Strengths of this study include rigorous study selection criteria which limited the meta-analysis to only published, randomized, placebo-controlled trials, utilization of the Covidence systematic review software platform to reduce reviewer error and bias when screening and extracting data, limited evidence of risk of bias in included studies, and utilization of Bayesian hierarchical modeling”

May combine two claims.

The proportion of lean mass loss observed with GLP1Ra-based therapy in this meta-analysis aligns with that seen after bariatric surgery (about 25-30%), although total achieved weight loss is significantly less.

“It is notable that the proportion of LM loss observed with GLP1Ra-based therapy in this meta-analysis aligns with bariatric surgery (~25-30%), yet the amount of total achieved WL is significantly less.”

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

A Bayesian hierarchical modeling approach was used and better accommodates study-specific heterogeneity and missing data than a traditional frequentist or fixed-effects approach.

“Strengths of this study include rigorous study selection criteria which limited the meta-analysis to only published, randomized, placebo-controlled trials, utilization of the Covidence systematic review software platform to reduce reviewer error and bias when screening and extracting data, limited evidence of risk of bias in included studies, and utilization of Bayesian hierarchical modeling”

May combine two claims.

A sensitivity analysis that treated the outlying standard deviation of Frossing et al. as a standard error produced only minor differences in point estimates and did not change the overall conclusions.

“Appendix A.4.a. presents sensitivity results assuming the outlying standard deviation of Frossing et al. (17) was a standard error. Only minor differences in point estimates resulted from this modified assumption; overall conclusions were not impacted.”

• cites [17] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The amount of lean mass lost during weight loss can be influenced by several factors that the meta-analysis could not fully account for.

“With that said, the amount of LM lost during weight loss can be influenced by several factors we could not fully account for in our meta-analysis, and interpretation of LM loss must also weigh its impact on relevant health outcomes.”

Classified as probably not a substantial claim.

DXA-acquired lean mass includes connective tissue, skin, organs, and water in addition to muscle mass.

“In particular, we recognize that DXA-acquired LM includes connective tissue, skin, organs, and water, in addition to the true outcome of interest (muscle mass).”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

There was limited evidence of risk of bias in the included studies.

“Strengths of this study include rigorous study selection criteria which limited the meta-analysis to only published, randomized, placebo-controlled trials, utilization of the Covidence systematic review software platform to reduce reviewer error and bias when screening and extracting data, limited evidence of risk of bias in included studies, and utilization of Bayesian hierarchical modeling”

Classified as probably not a substantial claim.

The focus on DXA-acquired musculoskeletal outcome measures limits the scope and inferential ability of the work.

“While selected due to clinical utility, focus on DXA-acquired musculoskeletal outcome measures does limit the scope and inferential ability of our work.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Among bariatric procedures, biliopancreatic diversion with duodenal switch and Roux-en-Y gastric bypass produce a greater percentage of fat-free mass loss than laparoscopic gastric banding, likely because of their malabsorptive nature.

“Even then, it is worth noting that among the bariatric procedures there are differences, with biliopancreatic diversion with duodenal switch and Roux-en-Y gastric bypass resulting in a greater percentage of fat free mass loss than laparoscopic gastric banding (25), likely due to their malabsorptive nature.”

• cites [25] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Because DXA-related terms often appeared only in supplementary materials, full-text database searching for these terms imposed an inherent limitation and possible exclusion of relevant studies.

“Lastly, as DXA-related terms often appeared exclusively in supplementary materials of relevant studies, full text database searching for these terms imposed an inherent limitation and possible exclusion of relevant studies.”