Network meta-analysis

Weight loss of 10 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 trialsEach dose separatelyOdds ratioSeparate part 2 of a disconnected network

Randomized trials

Treatments

2,770

Participants

498

Events

In plain language

Across 4 trials with 2,770 participants, 0 of 6 treatments had a clearly better result than semaglutide 1.0 mg subcutaneous once weekly on weight loss of 10 percent or more, 4 a clearly worse one, and for 2 the evidence could not tell them apart from semaglutide 1.0 mg subcutaneous once weekly. The most favorable estimate was for Semaglutide 2.0 mg subcutaneous once weekly: odds ratio 1.34 (95% credible interval 0.52 to 3.36).

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 Semaglutide 1.0 mg subcutaneous once weekly

Odds ratio. Higher values favor the treatment.

Versus Semaglutide 1.0 mg subcutaneous once weekly, 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 Semaglutide 1.0 mg subcutaneous once weekly
Treatment	Bayesian OR (95% CrI)	95% prediction interval	Frequentist OR (95% CI)	Verdict
Semaglutide 2.0 mg subcutaneous once weekly SEMA_SC_2p0MG_QW	1.34 (0.52 to 3.36)	0.34 to 5.19	1.35 (1.01 to 1.81)	Unclear
Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW	0.48 (0.20 to 1.61)	0.14 to 2.21	0.46 (0.30 to 0.69)	Unclear
Canagliflozin CANAGLIFLOZIN	0.34 (0.14 to 0.96)	0.09 to 1.39	0.33 (0.20 to 0.52)	Worse
Liraglutide 1.8 mg subcutaneous once daily LIRA_SC_1p8MG_QD	0.26 (0.10 to 0.80)	0.07 to 1.05		Worse
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	0.24 (0.10 to 0.77)	0.07 to 1.22	0.23 (0.14 to 0.38)	Worse
Dulaglutide 0.75 mg subcutaneous once weekly DULA_SC_0p75MG_QW	0.10 (0.04 to 0.35)	0.03 to 0.51	0.10 (0.05 to 0.19)	Worse

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	SEMA_SC_1p0MG_QW	SEMA_SC_2p0MG_QW	SEMA_SC_0p5MG_QW	CANAGLIFLOZIN	LIRA_SC_1p8MG_QD	DULA_SC_1p5MG_QW	DULA_SC_0p75MG_QW
SEMA_SC_1p0MG_QW	SEMA_SC_1p0MG_QW	0.75 0.30 to 1.94	2.06 0.62 to 4.99	2.98 1.04 to 7.37	3.88 1.25 to 10.52	4.12 1.30 to 9.82	9.66 2.84 to 25.79
SEMA_SC_2p0MG_QW	1.34 0.52 to 3.36	SEMA_SC_2p0MG_QW	2.78 0.63 to 9.12	3.98 0.94 to 14.73	5.16 1.19 to 19.95	5.52 1.15 to 18.47	12.93 2.67 to 46.42
SEMA_SC_0p5MG_QW	0.48 0.20 to 1.61	0.36 0.11 to 1.58	SEMA_SC_0p5MG_QW	1.45 0.39 to 6.11	1.88 0.44 to 7.98	1.99 0.73 to 5.42	4.71 1.44 to 14.43
CANAGLIFLOZIN	0.34 0.14 to 0.96	0.25 0.07 to 1.06	0.69 0.16 to 2.55	CANAGLIFLOZIN	1.30 0.31 to 5.36	1.38 0.31 to 5.03	3.23 0.68 to 12.70
LIRA_SC_1p8MG_QD	0.26 0.10 to 0.80	0.19 0.05 to 0.84	0.53 0.13 to 2.27	0.77 0.19 to 3.25	LIRA_SC_1p8MG_QD	1.05 0.25 to 4.26	2.49 0.55 to 10.67
DULA_SC_1p5MG_QW	0.24 0.10 to 0.77	0.18 0.05 to 0.87	0.50 0.18 to 1.37	0.72 0.20 to 3.22	0.95 0.23 to 4.03	DULA_SC_1p5MG_QW	2.38 0.76 to 7.28
DULA_SC_0p75MG_QW	0.10 0.04 to 0.35	0.08 0.02 to 0.38	0.21 0.07 to 0.70	0.31 0.08 to 1.48	0.40 0.09 to 1.82	0.42 0.14 to 1.31	DULA_SC_0p75MG_QW

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.270 (95% CrI 0.061 to 1.129), log scale
Residual deviance: 8.9 for 9 data points
DIC: 17.7 (pD 8.8)
Largest R-hat: 1.002
Smallest ESS: bulk 2,375, tail 2,187
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)

Frequentist check (netmeta)

Method: inverse variance, REML, OR
Tau: 0.000
Q (total): 0.00 on 0 df
Q (between designs): 0.00

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; 3 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 7 S000372	33.5	55.12	40	not_reported
SUSTAIN FORTE S001353	34.6	41.42	40	not_reported
SUSTAIN 8 S001847	not reported	46.19	52	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 1 of 4 trials
FlagBaseline, Sex: design means range from 41.4 (SEMA_SC_1p0MG_QW vs SEMA_SC_2p0MG_QW) to 56.8 (LIRA_SC_1p8MG_QD vs SEMA_SC_1p0MG_QW) percent female; threshold 15
NoteOutcome assessment, time point: selected time points span 40 to 52 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 3, other 1
NoteOutcome assessment, proportion method: mixed: not stated 1, not_stated 3
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: count_from_percent 8

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
SUSTAIN 7	40	full_analysis	not stated	not stated	not stated	not_stated	not stated	not stated	open_label	industry	2016	age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin background
SUSTAIN FORTE	40	full_analysis	not stated	not stated	not stated	not_stated	not stated	not stated	double_blind	industry	2019	T2D on metformin with or without SU; HbA1c 8.0 to 10.0 percent; duration at least 6 months
SUSTAIN 8	52	full_analysis	not stated	not stated	not stated	not_stated	not stated	not stated	double_blind	industry	2017	age 18 or older; HbA1c 7.0 to 10.5 percent; eGFR 60 or higher; metformin 1500 mg or maximum tolerated
S003432	52	other	not stated	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	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
SUSTAIN 7	A1	SEMA_SC_0p5MG_QW	40	arm, responders			43 / 301	count_from_percent	registry:outcomes
SUSTAIN 7	A2	SEMA_SC_1p0MG_QW	40	arm, responders			80 / 300	count_from_percent	registry:outcomes
SUSTAIN 7	A3	DULA_SC_0p75MG_QW	40	arm, responders			10 / 299	count_from_percent	registry:outcomes
SUSTAIN 7	A4	DULA_SC_1p5MG_QW	40	arm, responders			23 / 298	count_from_percent	registry:outcomes
SUSTAIN FORTE	A1	SEMA_SC_1p0MG_QW	40	arm, responders			109 / 481	count_from_percent	registry:outcomes
SUSTAIN FORTE	A2	SEMA_SC_2p0MG_QW	40	arm, responders			136 / 480	count_from_percent	registry:outcomes
SUSTAIN 8	A1	SEMA_SC_1p0MG_QW	52	arm, responders			69 / 298	count_from_percent	registry:outcomes
SUSTAIN 8	A2	CANAGLIFLOZIN	52	arm, responders			28 / 313	count_from_percent	registry:outcomes
S003432	A1	SEMA_SC_1p0MG_QW	52	contrast, or	1.411	0.347			R0053844:Table 1
S003432	A2	LIRA_SC_1p8MG_QD	52	contrast, or					R0053844:Table 1

Rerun this analysis yourself

Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.

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