Network meta-analysis

Percent body weight change

Overweight or obesity without diabetes (adults)

weeks 40 to 104 (target week 68)Not stated by the trialsDoses of a drug pooledMean difference

Randomized trials

Treatments

8,668

Participants

Trial arms

In plain language

Across 18 trials with 8,668 participants, 4 of 5 treatments had a clearly better result than placebo on percent body weight change, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Semaglutide tablet: mean difference -13.20 percentage points (95% credible interval -18.92 to -7.42).

Lower values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.

Network of trials

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Placebo

Mean difference in percentage points. Lower values favor the treatment.

Versus Placebo. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.

Effects of each treatment versus Placebo
Treatment	Bayesian MD (95% CrI)	95% prediction interval	Frequentist MD (95% CI)	Verdict
Semaglutide tablet SEMA_PO	-13.20 (-18.92 to -7.42)	-21.14 to -4.98	-13.60 (-18.79 to -8.41)	Better
Tirzepatide injection TIRZ_SC	-12.79 (-17.19 to -8.24)	-19.80 to -5.55	-12.91 (-16.90 to -8.92)	Better
Semaglutide injection SEMA_SC	-11.27 (-13.37 to -9.32)	-17.46 to -5.47	-11.30 (-13.14 to -9.46)	Better
Liraglutide injection LIRA_SC	-5.41 (-7.58 to -3.25)	-11.51 to 0.61	-5.43 (-7.37 to -3.50)	Better
Standard care or no added treatment STANDARD_CARE	1.73 (-2.84 to 5.98)	-5.68 to 8.72	1.74 (-2.23 to 5.72)	Unclear

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: mean difference of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.

Every treatment in a row compared with every treatment in a column
Row versus column	PLACEBO	SEMA_PO	TIRZ_SC	SEMA_SC	LIRA_SC	STANDARD_CARE
PLACEBO	PLACEBO	13.20 7.42 to 18.92	12.79 8.24 to 17.19	11.27 9.32 to 13.37	5.41 3.25 to 7.58	-1.73 -5.98 to 2.84
SEMA_PO	-13.20 -18.92 to -7.42	SEMA_PO	-0.46 -7.54 to 6.93	-1.91 -7.93 to 4.30	-7.81 -13.83 to -1.66	-14.93 -21.88 to -7.56
TIRZ_SC	-12.79 -17.19 to -8.24	0.46 -6.93 to 7.54	TIRZ_SC	-1.53 -5.74 to 3.11	-7.37 -12.07 to -2.45	-14.51 -20.21 to -8.19
SEMA_SC	-11.27 -13.37 to -9.32	1.91 -4.30 to 7.93	1.53 -3.11 to 5.74	SEMA_SC	-5.84 -8.58 to -3.34	-13.03 -17.15 to -8.63
LIRA_SC	-5.41 -7.58 to -3.25	7.81 1.66 to 13.83	7.37 2.45 to 12.07	5.84 3.34 to 8.58	LIRA_SC	-7.14 -11.31 to -2.71
STANDARD_CARE	1.73 -2.84 to 5.98	14.93 7.56 to 21.88	14.51 8.19 to 20.21	13.03 8.63 to 17.15	7.14 2.71 to 11.31	STANDARD_CARE

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 2.689 (95% CrI 1.733 to 4.278)
Residual deviance: 39.9 for 38 data points
DIC: 75.7 (pD 35.8)
Largest R-hat: 1.001
Smallest ESS: bulk 3,301, tail 4,580
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 35^2); PR03 N(0, 17.5^2); PR07 half normal(0, 3.5^2) on tau

Frequentist check (netmeta)

Method: inverse variance, REML, MD
Tau: 2.548
I squared: 84%
Q (total): 96.25 on 15 df, P = 0.000
Q (between designs): 52.00, P = 0.000

Inconsistency

Do trials comparing two treatments directly agree with the indirect evidence through other treatments?

No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting; the between designs Q above is the global check.

Small study effects

A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.

Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.

Baseline characteristics of the trials

The baseline value of each effect modifier or prognostic factor that applies here, per trial: mean or percent over arms, weighted by the number randomized. A note under a value names a stand in (a median for a mean, 100 minus the male share, Asian subgroup rows, an all Asian site list); "not reported" means no source of the trial prints it.

Baseline effect modifiers and prognostic factors per trial
Trial	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 12 of 18	Type 2 diabetes share in weight trials (percent of participants) effect modifier; 18 of 18	Sex (percent female) effect modifier, prognostic factor; 18 of 18	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 14 of 18	Treatment duration (weeks) effect modifier; 18 of 18	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 18 of 18
NCT01272219 S000492	38.3	0 population codes	78.5	not reported	56	standard
SURMOUNT-5 S000093	39.4	0 population codes	64.65	2.4	72	standard
STEP 5 S000214	38.55	0 population codes	77.6	0.65	104	standard
S-LITE S000371	32.62	0 population codes	64.51	not reported	52	intensive
BARI-STEP S000434	41.5	10	82.85	2.85	68	standard
STEP 10 S000832	39.9	0 population codes	71.01	4.35	52	not_reported
NCT03038620 S000866	37.65	0 population codes	92.25	0	40	standard
SURMOUNT-CN S001086	body weight 91.8 kg	0 population codes	49.05	100	52	standard
NCT00781937 S001278	35.6	0 population codes	81.28	0.24	56	standard
STEP7 S001288	not reported	0 population codes	45.33	90.67	44	standard
STABLE Wt Loss S001294	37.48	0 population codes	78.36	4.2	60	not_reported;standard
OASIS 1 S001472	not reported	0 population codes	72.71	10.79	68	not_reported
STEP 8 S001600	not reported	0 population codes	78.4	3.85	68	standard
STRIVE S001687	45.96	35.5	64.28	3.56	104	intensive
STEP 6 S002102	not reported	0 population codes	36.91	100	68	not_reported
NCT02453711 S002317	body weight 111.5 kg	0 population codes	64.68	0.94	52	standard
S003017 S003017	38.05	0 population codes	87.5	not reported	52.14	standard
S003032 S003032	39.06	0 population codes	67.5	not reported	34.76	intensive

Comparability of the trials

Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.

FlagBaseline, Baseline BMI or body weight: not reported by 6 of 18 trials
FlagBaseline, Baseline BMI or body weight: design means range from 36.4 (LIRA_SC vs PLACEBO) to 46.0 (LIRA_SC vs STANDARD_CARE) kg/m2; threshold 3
FlagBaseline, Type 2 diabetes share in weight trials: design means range from 0.0 (LIRA_SC vs PLACEBO) to 35.5 (LIRA_SC vs STANDARD_CARE) percent of participants; threshold 20
FlagBaseline, Sex: design means range from 49.0 (PLACEBO vs TIRZ_SC) to 80.8 (LIRA_SC vs PLACEBO) percent female; threshold 15
FlagBaseline, Asian ancestry or region: not reported by 4 of 18 trials
FlagBaseline, Asian ancestry or region: design means range from 0.1 (LIRA_SC vs PLACEBO) to 100.0 (PLACEBO vs TIRZ_SC) percent Asian; threshold 30
FlagBaseline, Treatment duration: design means range from 34.8 (SEMA_SC vs STANDARD_CARE) to 104.0 (LIRA_SC vs STANDARD_CARE) weeks; threshold 26
FlagHeterogeneity, tau above threshold: tau 2.69 exceeds the outcome threshold 2.5; the flags of this network are candidate explanations
NoteOutcome assessment, time point: selected time points span 40 to 78 weeks
NoteOutcome assessment, analysis set: mixed: completers 4, full_analysis 9, modified_itt 1, other 1, per_protocol 1, randomized 2
NoteOutcome assessment, definition: mixed: not stated 14, percent change in body weight 1, percent change in body weight from baseline 1, percent change in body weight from randomization after the diet to end of treatment 1, percent change in fasting weight from randomization 1
NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 1, not stated 17
NoteRisk of bias, blinding: mixed: double_blind 15, open_label 3
NoteRisk of bias, funding: mixed: industry 15, mixed 2, non_industry 1
NoteData handling, input conversions: arms_combined 5, n_randomized 4

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT01272219	56	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2011	age 18 or more; BMI 30 or more, or 27 or more with hypertension or dyslipidemia; no diabetes; prediabetes allowed
SURMOUNT-5	72	other	not stated	not stated	not stated	not stated	hypothetical	not stated	open_label	industry	2023	adults; BMI 30 or more, or 27 with complication; no diabetes
STEP 5	52	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2018	age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
S-LITE	52	per_protocol	percent change in body weight from randomization after the diet to end of treatment	not stated	not stated	not stated	not stated	not stated	double_blind	mixed	2016	age 18 to 65; BMI 32 to 43; no diabetes; at least 5 percent loss on 8 week low calorie diet
BARI-STEP	68	modified_itt	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	mixed	2022	age 18 to 65; at least 1 year after primary bypass or sleeve; less than 20 percent weight loss from surgery
STEP 10	52	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	Adults with obesity and prediabetes; diabetes excluded
NCT03038620	40	completers	percent change in body weight from baseline	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	age 35 or more; BMI 30 or more, or 27 or more with metabolic syndrome; no diabetes
SURMOUNT-CN	78	completers	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	Chinese adults; BMI 28 or more, or 24 or more with a weight related comorbidity; no diabetes
NCT00781937	56	full_analysis	percent change in fasting weight from randomization	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2008	BMI 30 or more or 27 with comorbidity; no diabetes; at least 5 percent loss on run in
STEP7	44	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2020	age 18 or older; BMI 30 or more, or 27 or more with a weight related comorbidity including T2D
STABLE Wt Loss	60	randomized	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2022	age 18 to 70; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c 6.5 percent or less
OASIS 1	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2021	overweight or obesity
STEP 8	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019	age 18 or older; BMI 30 or higher, or 27 with a weight related comorbidity; no type 2 diabetes
STRIVE	52	completers	not stated	not stated	not stated	not stated	not stated	not stated	open_label	industry	2017	age 18 to 75; BMI 35 or more plus prediabetes, T2D, hypertension or sleep apnea; no insulin or GLP-1 RA
STEP 6	68	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019
NCT02453711	52	full_analysis	percent change in body weight	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2015	BMI 30 or more without diabetes
S003017	52.14	randomized	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2019	age 20 to 65; BMI above 35; 12 to 36 months after bariatric surgery with suboptimal stable weight loss or regain
S003032	52.14	completers	not stated	not stated	not stated	not stated	not stated	not stated	open_label	non_industry		age 18 to 65; BMI 27 or higher; scheduled for intragastric balloon

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the mean difference on the analysis scale against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Value	SE	Events / N	Flags	Source
SURMOUNT-5	A1	TIRZ_SC	72	arm, percent_change	-20.200	0.590	318		registry:outcomes
SURMOUNT-5	A2	SEMA_SC	72	arm, percent_change	-13.700	0.590	318		registry:outcomes
STEP 5	A1	SEMA_SC	52	arm, percent_change	-15.800	0.762	149		registry:outcomes
STEP 5	A2	PLACEBO	52	arm, percent_change	-3.300	0.563	129		registry:outcomes
S-LITE	A1+A2	PLACEBO	52	arm, percent_change	4.180	1.116	65	arms_combined	R0006966:Supplementary Table 2
S-LITE	A3+A4	LIRA_SC	52	arm, percent_change	-4.140	1.087	65	arms_combined	R0006966:Supplementary Table 2
BARI-STEP	A1	PLACEBO	68	arm, percent_change	0.900	2.200	29		R0014003:Results
BARI-STEP	A2	SEMA_SC	68	arm, percent_change	-18.200	2.300	34		R0014003:Results
NCT01272219	A1	LIRA_SC	56	arm, percent_change	-7.980	0.135	2,432		registry:outcomes
NCT01272219	A2	PLACEBO	56	arm, percent_change	-2.620	0.164	1,220		registry:outcomes
STEP 10	A1	SEMA_SC	52	arm, percent_change	-14.400	0.696	129		registry:outcomes
STEP 10	A2	PLACEBO	52	arm, percent_change	-2.700	0.529	66		registry:outcomes
NCT03038620	A1	LIRA_SC	40	arm, percent_change	-6.590	0.562	73		registry:outcomes
NCT03038620	A2	PLACEBO	40	arm, percent_change	-1.190	0.631	55		registry:outcomes
SURMOUNT-CN	A1+A2	TIRZ_SC	78	arm, percent_change	-9.608	0.854	103	arms_combined	R0007857:Supplement Table S2
SURMOUNT-CN	A3	PLACEBO	78	arm, percent_change	-2.472	1.126	39		R0007857:Supplement Table S2
NCT00781937	A1	LIRA_SC	56	arm, percent_change	-6.110	0.660	194		registry:outcomes
NCT00781937	A2	PLACEBO	56	arm, percent_change	-0.050	0.630	188		registry:outcomes
STEP7	A1	SEMA_SC	44	arm, percent_change	-12.500	0.480	238		registry:outcomes
STEP7	A2	PLACEBO	44	arm, percent_change	-3.600	0.548	116		registry:outcomes
STABLE Wt Loss	A1	SEMA_SC	60	arm, percent_change	-15.100	1.300	72	n_randomized	R0013679:Table 3
STABLE Wt Loss	A2	PLACEBO	60	arm, percent_change	-3.400	1.800	48	n_randomized	R0013679:Table 3
OASIS 1	A1	SEMA_PO	68	arm, percent_change	-15.800	0.579	317		registry:outcomes
OASIS 1	A2	PLACEBO	68	arm, percent_change	-2.200	0.419	295		registry:outcomes
STEP 8	A1	SEMA_SC	68	arm, percent_change	-16.400	0.971	117		registry:outcomes
STEP 8	A2	LIRA_SC	68	arm, percent_change	-6.400	0.712	117		registry:outcomes
STEP 8	A3	PLACEBO	68	arm, percent_change	-1.600	0.974	78		registry:outcomes
STRIVE	A1	STANDARD_CARE	52	arm, percent_change	-2.700	0.705	93		R0020855:Table 2
STRIVE	A2	LIRA_SC	52	arm, percent_change	-8.100	0.508	201		R0020855:Table 2
STEP 6	A1+A2	SEMA_SC	68	arm, percent_change	-12.221	0.498	291	arms_combined	registry:outcomes
STEP 6	A3	PLACEBO	68	arm, percent_change	-1.900	0.590	100		registry:outcomes
NCT02453711	A1+A2+A3+A4+A5+A6+A7	SEMA_SC	52	arm, percent_change	-11.346	0.339	672	arms_combined	registry:outcomes
NCT02453711	A8	LIRA_SC	52	arm, percent_change	-7.760	0.850	96		registry:outcomes
NCT02453711	A9	PLACEBO	52	arm, percent_change	-2.290	0.740	123		registry:outcomes
S003017	A1	LIRA_SC	52.14	arm, percent_change	-4.400	0.900	24	n_randomized	R0016758:Results
S003017	A2	PLACEBO	52.14	arm, percent_change	1.400	1.000	24	n_randomized	R0016758:Results
S003032	A1	STANDARD_CARE	52.14	arm, percent_change	-13.470	0.461	20		R0015729:Table 4
S003032	A2	SEMA_SC	52.14	arm, percent_change	-28.210	0.472	20		R0015729:Table 4

Rerun this analysis yourself

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