LivingGLP1
Network meta-analysis

Discontinuation due to gastrointestinal adverse events

Overweight or obesity without diabetes (adults)

longest follow-upRecorded harmsDoses of a drug pooledHazard ratio (from event counts)
12
Randomized trials
11
Treatments
3,784
Participants
126
Events

In plain language

Across 12 trials with 3,784 participants, 0 of 10 treatments had a clearly better result than placebo on discontinuation due to gastrointestinal adverse events, 2 a clearly worse one, and for 8 the evidence could not tell them apart from placebo. The most favorable estimate was for Standard care or no added treatment: hazard ratio (from event counts) 0.25 (95% credible interval 0.01 to 4.75).

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.
ALENIG_POCT388_SCEFPE_SCHRS7535_POLIRA_SCMAZD_SCPLACEBOSEMA_SCSTANDARD_CARETG103_SCTIRZ_SC
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

Hazard ratio (from event counts). Lower values favor the treatment.
0.010.020.050.10.20.250.51245102050100← favors treatmentfavors reference →Standard care or no added treatm…Tg103 scCt388 scTirzepatide injectionHRS-7535 tabletAlenig poMazdutide injectionEfpe scSemaglutide injectionLiraglutide injection
Versus Placebo, log scale. 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
TreatmentBayesian HR (95% CrI)95% prediction intervalFrequentist HR (95% CI)Verdict
Standard care or no added treatment
STANDARD_CARE
0.25 (0.01 to 4.75)0.01 to 5.44Unclear
Tg103 sc
TG103_SC
0.45 (0.01 to 37.52)0.00 to 38.58Unclear
Ct388 sc
CT388_SC
0.48 (0.01 to 39.54)0.01 to 40.05Unclear
Tirzepatide injection
TIRZ_SC
0.63 (0.02 to 12.68)0.02 to 13.45Unclear
HRS-7535 tablet
HRS7535_PO
2.07 (0.14 to 78.04)0.13 to 79.57Unclear
Alenig po
ALENIG_PO
4.01 (0.79 to 37.90)0.71 to 42.98Unclear
Mazdutide injection
MAZD_SC
4.56 (0.32 to 149)0.30 to 154Unclear
Efpe sc
EFPE_SC
5.27 (1.07 to 48.14)0.95 to 54.34Worse
Semaglutide injection
SEMA_SC
5.29 (2.10 to 14.12)1.60 to 17.29Worse
Liraglutide injection
LIRA_SC
10.56 (0.99 to 253)0.87 to 255Unclear

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: hazard ratio (from event counts) 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 columnPLACEBOSTANDARD_CARETG103_SCCT388_SCTIRZ_SCHRS7535_POALENIG_POMAZD_SCEFPE_SCSEMA_SCLIRA_SC
PLACEBOPLACEBO3.93
0.21 to 96.29		2.24
0.03 to 192		2.08
0.03 to 188		1.58
0.08 to 40.62		0.48
0.01 to 7.15		0.25
0.03 to 1.27		0.22
0.01 to 3.08		0.19
0.02 to 0.94		0.19
0.07 to 0.48		0.09
0.00 to 1.01
STANDARD_CARE0.25
0.01 to 4.75		STANDARD_CARE0.56
0.00 to 116		0.54
0.00 to 117		0.42
0.06 to 2.18		0.11
0.00 to 7.11		0.06
0.00 to 1.97		0.05
0.00 to 3.19		0.04
0.00 to 1.40		0.05
0.00 to 1.09		0.02
0.00 to 1.11
TG103_SC0.45
0.01 to 37.52		1.78
0.01 to 424		TG103_SC0.95
0.00 to 475		0.71
0.00 to 174		0.19
0.00 to 35.47		0.10
0.00 to 12.81		0.09
0.00 to 16.30		0.08
0.00 to 10.15		0.08
0.00 to 7.55		0.04
0.00 to 5.76
CT388_SC0.48
0.01 to 39.54		1.86
0.01 to 414		1.05
0.00 to 600		CT388_SC0.78
0.00 to 172		0.21
0.00 to 39.54		0.11
0.00 to 13.36		0.09
0.00 to 17.67		0.08
0.00 to 9.34		0.09
0.00 to 7.71		0.04
0.00 to 7.40
TIRZ_SC0.63
0.02 to 12.68		2.39
0.46 to 17.10		1.40
0.01 to 320		1.28
0.01 to 291		TIRZ_SC0.28
0.00 to 18.08		0.14
0.00 to 4.92		0.13
0.00 to 8.59		0.11
0.00 to 3.70		0.12
0.00 to 2.88		0.06
0.00 to 3.15
HRS7535_PO2.07
0.14 to 78.04		8.91
0.14 to 1144		5.21
0.03 to 1567		4.82
0.03 to 1494		3.52
0.06 to 463		HRS7535_PO0.51
0.02 to 26.51		0.47
0.01 to 37.92		0.39
0.01 to 20.64		0.40
0.02 to 16.35		0.20
0.00 to 14.58
ALENIG_PO4.01
0.79 to 37.90		17.50
0.51 to 774		10.09
0.08 to 1372		9.23
0.07 to 1320		6.90
0.20 to 305		1.97
0.04 to 60.21		ALENIG_PO0.90
0.02 to 28.43		0.76
0.05 to 11.14		0.75
0.11 to 8.32		0.39
0.01 to 10.23
MAZD_SC4.56
0.32 to 149		18.58
0.31 to 2218		10.94
0.06 to 2577		10.55
0.06 to 2641		7.58
0.12 to 836		2.11
0.03 to 181		1.11
0.04 to 55.09		MAZD_SC0.83
0.03 to 37.99		0.87
0.05 to 28.49		0.43
0.01 to 28.78
EFPE_SC5.27
1.07 to 48.14		22.99
0.71 to 1090		12.70
0.10 to 1919		11.94
0.11 to 1701		8.96
0.27 to 397		2.59
0.05 to 77.16		1.32
0.09 to 18.53		1.21
0.03 to 34.60		EFPE_SC0.99
0.15 to 10.56		0.51
0.01 to 14.65
SEMA_SC5.29
2.10 to 14.12		21.01
0.92 to 608		12.21
0.13 to 1105		11.36
0.13 to 1134		8.53
0.35 to 249		2.52
0.06 to 46.92		1.33
0.12 to 8.83		1.16
0.04 to 19.26		1.01
0.09 to 6.49		SEMA_SC0.51
0.02 to 6.97
LIRA_SC10.56
0.99 to 253		44.05
0.90 to 3858		25.68
0.17 to 5075		23.60
0.14 to 5705		17.78
0.32 to 1490		4.99
0.07 to 316		2.58
0.10 to 91.82		2.31
0.03 to 147		1.96
0.07 to 70.86		1.96
0.14 to 55.14		LIRA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.202 (95% CrI 0.038 to 0.897), log scale
Residual deviance
17.7 for 24 data points
DIC
30.4 (pD 12.7)
Largest R-hat
1.001
Smallest ESS
bulk 3,906, tail 3,163
Divergent transitions
0
Convergence
All criteria met
Priors
PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.99, 1.74^2) on tau^2 (Withdrawals/drop-outs, pharm vs placebo control)

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.

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
TrialSex (percent female)
effect modifier, prognostic factor; 12 of 12
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 10 of 12
TOGETHER-PsO
S000032
44.93.3
STEP 1
S000144
74.0713.33
STEP 5
S000214
77.60.65
NCT03041792
S000418
67.691.81
NCT02075281
S000743
76.358.49
ACCESS
S000899
54.351.74
NCT05623839
S001559
50not reported
TOGETHER-PsA
S001889
69.752.2
NCT06250946
S002275
48.49100
region: all sites in Asia
NCT04838405
S002824
56.2512.5
S003032
S003032
67.5not reported
NCT04855292
S003063
37.5100
region: all sites in Asia

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, Sex: design means range from 37.5 (PLACEBO vs TG103_SC) to 76.3 (EFPE_SC vs PLACEBO) percent female; threshold 15
  • FlagBaseline, Asian ancestry or region: design means range from 1.7 (ALENIG_PO vs PLACEBO) to 100.0 (HRS7535_PO vs PLACEBO) percent Asian; threshold 30
  • NoteOutcome assessment, time point: selected time points span 6 to 111 weeks
  • NoteOutcome assessment, analysis set: mixed: completers 1, randomized 1, safety 10
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: not stated 11, while_on_treatment 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: not stated 11, treatment_policy 1
  • NoteRisk of bias, blinding: mixed: double_blind 9, open_label 2, single_blind 1
  • NoteRisk of bias, funding: mixed: industry 11, non_industry 1
  • NoteData handling, input conversions: arms_combined 6, printed_denominator 4
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
TOGETHER-PsO36safetynot statednot statednot statednot statednot statednot statedopen_labelindustry2024adults; moderate to severe plaque psoriasis; PASI 12 or more; BMI 30 or more, or 27 to 30 with comorbidity
STEP 168safetynot statednot statednot statednot statedwhile_on_treatmenttreatment_policydouble_blindindustry2018adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent
STEP 5111safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2018age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent
NCT0304179210.43safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2017age 18 to 75; BMI 30 to 40; no diabetes; HbA1c below 6.5 percent
NCT0207528120safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2014age 18 to 64 years; BMI 30 to 42, or 27 to 30 with comorbidity; FPG below 7 mmol/L; HbA1c 6.5 percent or less; no diabetes
ACCESS36safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2024age 18 to 79; BMI 30 or more, or 27 or more with comorbidity; HbA1c below 6.5 percent; weight above 80 kg; no diabetes
NCT0562383927safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2022age 18 to 70; BMI 27 to 50; HbA1c below 6.5 percent; no diabetes
TOGETHER-PsA36safetynot statednot statednot statednot statednot statednot statedsingle_blindindustry2024age 18 to 80; active psoriatic arthritis; BMI 30 or more, or 27 to 30 with a weight related comorbidity
NCT0625094636safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2024age 18 to 65; BMI 28 to 40; no diabetes, HbA1c below 6.5 percent
NCT048384056randomizednot statednot statednot statednot statednot statednot stateddouble_blindindustry2021age 18 to 65, BMI 25 or more (30 or more in cohorts 7 and 8), no diabetes
S00303252.14completersnot statednot statednot statednot statednot statednot statedopen_labelnon_industryage 18 to 65; BMI 27 or higher; scheduled for intragastric balloon
NCT0485529214safetynot statednot statednot statednot statednot statednot stateddouble_blindindustry2021age 18 to 75; BMI 26 or more; weight 60 kg or more; HbA1c below 6.5; no diabetes

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the hazard ratio (from event counts) on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.
Trial data entering this analysis
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
TOGETHER-PsOA1STANDARD_CARE36arm, events1 / 134printed_denominatorR0014237:Table 3
TOGETHER-PsOA2TIRZ_SC36arm, events1 / 138printed_denominatorR0014237:Table 3
STEP 1A1SEMA_SC68arm, events59 / 1,306R0023399:Table 3
STEP 1A2PLACEBO68arm, events5 / 655R0023399:Table 3
STEP 5A1SEMA_SC111arm, events6 / 152R0021896:Table 3
STEP 5A2PLACEBO111arm, events1 / 152R0021896:Table 3
NCT03041792A1LIRA_SC10.43arm, events4 / 32R0023522:Results
NCT03041792A2PLACEBO10.43arm, events0 / 29R0023522:Results
NCT02075281A1PLACEBO20arm, events1 / 60R0011218:Supplement Table S6
NCT02075281A2+A3+A4+A5EFPE_SC20arm, events23 / 237arms_combinedR0011218:Supplement Table S6
ACCESSA1+A2+A3ALENIG_PO36arm, events14 / 174arms_combinedR0000892:Table 2
ACCESSA4PLACEBO36arm, events1 / 56R0000892:Table 2
NCT05623839A1PLACEBO27arm, events0 / 8R0013210:Results
NCT05623839A2+A3MAZD_SC27arm, events3 / 24arms_combinedR0013210:Results
TOGETHER-PsAA1STANDARD_CARE36arm, events1 / 132printed_denominatorR0018951:Table 3
TOGETHER-PsAA2TIRZ_SC36arm, events4 / 138printed_denominatorR0018951:Table 3
NCT06250946A1PLACEBO36arm, events0 / 46R0001289:Supplement Table 6
NCT06250946A2+A3+A4+A5HRS7535_PO36arm, events2 / 189arms_combinedR0001289:Supplement Table 6
NCT04838405A10+A8+A9CT388_SC6arm, events0 / 18arms_combinedR0007991:Table 3
NCT04838405A7PLACEBO6arm, events0 / 6R0007991:Table 3
S003032A1STANDARD_CARE52.14arm, events0 / 25R0015729:Table 2
S003032A2SEMA_SC52.14arm, events0 / 25R0015729:Table 2
NCT04855292A1+A2+A3TG103_SC14arm, events0 / 36arms_combinedR0022276:Results
NCT04855292A4PLACEBO14arm, events0 / 12R0022276:Results

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