Network meta-analysis

Weight loss of 5 percent or more

Type 2 diabetes (adults); background therapy: one or more non insulin glucose lowering drugs

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

Randomized trials

Treatments

2,465

Participants

1,000

Events

In plain language

Across 4 trials with 2,465 participants, 2 of 5 treatments had a clearly better result than placebo on weight loss of 5 percent or more, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for Semaglutide injection: odds ratio 8.33 (95% credible interval 1.50 to 26.73).

Higher 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

Odds ratio. Higher values favor the treatment.

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
Treatment	Bayesian OR (95% CrI)	95% prediction interval	Verdict
Semaglutide injection SEMA_SC	8.33 (1.50 to 26.73)	1.03 to 32.51	Better
Canagliflozin CANAGLIFLOZIN	6.37 (0.80 to 24.79)	0.54 to 29.75	Unclear
Cotadutide injection COTA_SC	4.53 (1.32 to 12.28)	0.86 to 16.72	Better
Liraglutide injection LIRA_SC	2.90 (0.82 to 7.48)	0.51 to 10.38	Unclear
Dulaglutide injection DULA_SC	2.58 (0.38 to 9.65)	0.27 to 12.03	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: odds ratio 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_SC	CANAGLIFLOZIN	COTA_SC	LIRA_SC	DULA_SC
PLACEBO	PLACEBO	0.12 0.04 to 0.67	0.16 0.04 to 1.25	0.22 0.08 to 0.76	0.35 0.13 to 1.22	0.39 0.10 to 2.66
SEMA_SC	8.33 1.50 to 26.73	SEMA_SC	1.32 0.53 to 3.91	1.89 0.37 to 6.00	2.90 0.86 to 7.18	3.24 1.22 to 8.62
CANAGLIFLOZIN	6.37 0.80 to 24.79	0.76 0.26 to 1.87	CANAGLIFLOZIN	1.44 0.19 to 5.70	2.21 0.41 to 7.09	2.47 0.60 to 9.08
COTA_SC	4.53 1.32 to 12.28	0.53 0.17 to 2.71	0.69 0.18 to 5.16	COTA_SC	1.54 0.61 to 4.58	1.72 0.43 to 11.16
LIRA_SC	2.90 0.82 to 7.48	0.35 0.14 to 1.16	0.45 0.14 to 2.42	0.65 0.22 to 1.64	LIRA_SC	1.11 0.33 to 5.38
DULA_SC	2.58 0.38 to 9.65	0.31 0.12 to 0.82	0.40 0.11 to 1.68	0.58 0.09 to 2.32	0.90 0.19 to 3.03	DULA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.290 (95% CrI 0.062 to 1.200), log scale
Residual deviance: 8.2 for 8 data points
DIC: 16.0 (pD 7.8)
Largest R-hat: 1.002
Smallest ESS: bulk 1,777, tail 2,554
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.53, 1.58^2) on tau^2 (General physical health indicators, pharm vs pharm)

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
Trial	Baseline BMI or body weight (kg/m2) effect modifier, prognostic factor; 2 of 4	Sex (percent female) effect modifier, prognostic factor; 4 of 4	Treatment duration (weeks) effect modifier; 4 of 4	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 4 of 4
SUSTAIN 8 S001847	not reported	46.19	52	not_reported
NCT03235050 S000257	not reported	53.72	54	not_reported
SUSTAIN 7 S000372	33.5	55.12	40	not_reported
S003432 S003432	34.45	56.85	52	not_reported

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 2 of 4 trials
NoteOutcome assessment, time point: selected time points span 40 to 54 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 2, other 1, per_protocol 1
NoteOutcome assessment, proportion method: mixed: not stated 2, not_stated 2
NoteRisk of bias, blinding: mixed: double_blind 2, open_label 2
NoteRisk of bias, funding: mixed: industry 3, non_industry 1
NoteData handling, input conversions: arms_combined 3, count_from_percent 4

Comparability items per trial
Trial	funding	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	start year	Eligibility
SUSTAIN 8	industry	52	full_analysis	not stated	not stated	not stated	not_stated	not stated	not stated	double_blind	2017	age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated
NCT03235050	industry	54	per_protocol	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	2017	age 18 or older; BMI 25 or higher; HbA1c 7.0 to 10.5 percent; on metformin
SUSTAIN 7	industry	40	full_analysis	not stated	not stated	not stated	not_stated	not stated	not stated	open_label	2016	age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background
S003432	non_industry	52	other	not stated	not stated	not stated	not stated	not stated	not stated	open_label	2020	age 18 to 65; type 2 diabetes 1 year or more; HbA1c 7.0 to 10.5 percent; BMI 30 or higher; stable metformin

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds ratio on the analysis scale (log) 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
NCT03235050	A1	PLACEBO	54	arm, responders			9 / 91		R0016374:Results
NCT03235050	A2	LIRA_SC	54	arm, responders			32 / 104		R0016374:Results
NCT03235050	A3+A4+A5	COTA_SC	54	arm, responders			176 / 461	arms_combined	R0016374:Results
SUSTAIN 7	A1+A2	SEMA_SC	40	arm, responders			321 / 601	count_from_percent;arms_combined	registry:outcomes
SUSTAIN 7	A3+A4	DULA_SC	40	arm, responders			158 / 597	count_from_percent;arms_combined	registry:outcomes
SUSTAIN 8	A1	SEMA_SC	52	arm, responders			157 / 298	count_from_percent	registry:outcomes
SUSTAIN 8	A2	CANAGLIFLOZIN	52	arm, responders			147 / 313	count_from_percent	registry:outcomes
S003432	A1	SEMA_SC	52	contrast, or	1.235	0.290			R0053844:Table 1
S003432	A2	LIRA_SC	52	contrast, or					R0053844:Table 1

Rerun this analysis yourself

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