Network meta-analysis

Weight loss of 5 percent or more

Type 2 diabetes (adults); background therapy: basal insulin with or without non insulin drugs

weeks 40 to 104 (target week 68)Hypothetical (as if everyone stayed on treatment)Each dose separatelyOdds ratio

Randomized trials

Treatments

546

Participants

210

Events

In plain language

Across 2 trials with 546 participants, 3 of 4 treatments had a clearly better result than placebo on weight loss of 5 percent or more, and for 1 the evidence could not tell it apart from placebo. The most favorable estimate was for Orforglipron 12 mg oral once daily: odds ratio 5.10 (95% credible interval 1.43 to 13.70).

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	Frequentist OR (95% CI)	Verdict
Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD	5.10 (1.43 to 13.70)	1.05 to 19.34	5.62 (3.20 to 9.86)	Better
Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD	4.81 (1.41 to 12.84)	0.91 to 18.74	5.28 (3.02 to 9.24)	Better
Liraglutide 3.0 mg subcutaneous once daily LIRA_SC_3p0MG_QD	4.49 (1.38 to 11.70)	0.93 to 16.59		Better
Orforglipron 3 mg oral once daily ORFO_PO_3MG_QD	2.63 (0.75 to 6.79)	0.50 to 10.18	2.86 (1.62 to 5.04)	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	ORFO_PO_12MG_QD	ORFO_PO_36MG_QD	LIRA_SC_3p0MG_QD	ORFO_PO_3MG_QD
PLACEBO	PLACEBO	0.20 0.07 to 0.70	0.21 0.08 to 0.71	0.22 0.09 to 0.73	0.38 0.15 to 1.34
ORFO_PO_12MG_QD	5.10 1.43 to 13.70	ORFO_PO_12MG_QD	1.06 0.35 to 3.27	1.15 0.23 to 4.90	1.95 0.65 to 5.84
ORFO_PO_36MG_QD	4.81 1.41 to 12.84	0.95 0.31 to 2.84	ORFO_PO_36MG_QD	1.08 0.24 to 4.65	1.83 0.64 to 5.64
LIRA_SC_3p0MG_QD	4.49 1.38 to 11.70	0.87 0.20 to 4.31	0.93 0.22 to 4.24	LIRA_SC_3p0MG_QD	1.71 0.39 to 8.30
ORFO_PO_3MG_QD	2.63 0.75 to 6.79	0.51 0.17 to 1.53	0.55 0.18 to 1.57	0.58 0.12 to 2.56	ORFO_PO_3MG_QD

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.304 (95% CrI 0.072 to 1.266), log scale
Residual deviance: 5.1 for 5 data points
DIC: 10.1 (pD 5.0)
Largest R-hat: 1.002
Smallest ESS: bulk 2,586, tail 2,561
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.29, 1.53^2) on tau^2 (General physical health indicators, pharm vs placebo control)

Frequentist check (netmeta)

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

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 2	Sex (percent female) effect modifier, prognostic factor; 2 of 2	Treatment duration (weeks) effect modifier; 2 of 2	Lifestyle co-intervention intensity (none standard intensive) effect modifier, prognostic factor; 2 of 2
SCALE™ Insulin S000159	35.6	52.27	56	intensive
ACHIEVE-5 S001044	30.8	47.07	40	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: design means range from 30.8 (ORFO_PO_12MG_QD vs ORFO_PO_36MG_QD vs ORFO_PO_3MG_QD vs PLACEBO) to 35.6 (LIRA_SC_3p0MG_QD vs PLACEBO) kg/m2; threshold 3
FlagBaseline, Lifestyle co-intervention intensity: each design has a different category: LIRA_SC_3p0MG_QD vs PLACEBO = intensive; ORFO_PO_12MG_QD vs ORFO_PO_36MG_QD vs ORFO_PO_3MG_QD vs PLACEBO = not_reported
FlagOutcome assessment, analysis set: confounded with design: full_analysis 1, randomized 1
FlagOutcome assessment, proportion method: confounded with design: not stated 1, not_stated 1
FlagOutcome assessment, intercurrent events (rescue): confounded with design: hypothetical 1, not stated 1
NoteOutcome assessment, time point: selected time points span 40 to 56 weeks
NoteData handling, input conversions: count_from_percent 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
SCALE™ Insulin	56	full_analysis	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	2017	age 18 or older; BMI 27 or higher; HbA1c 6.0 to 10 percent; basal insulin plus up to 2 oral drugs
ACHIEVE-5	40	randomized	not stated	not stated	not stated	not_stated	hypothetical	hypothetical	double_blind	industry	2023	adults with T2D on insulin glargine with or without metformin or SGLT2 inhibitor

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
SCALE™ Insulin	A1	LIRA_SC_3p0MG_QD	56	contrast, or	1.554	0.226			registry:outcomes
SCALE™ Insulin	A2	PLACEBO	56	contrast, or					registry:outcomes
ACHIEVE-5	A1	PLACEBO	40	arm, responders			23 / 141	count_from_percent	registry:outcomes
ACHIEVE-5	A2	ORFO_PO_3MG_QD	40	arm, responders			49 / 137	count_from_percent	registry:outcomes
ACHIEVE-5	A3	ORFO_PO_12MG_QD	40	arm, responders			69 / 132	count_from_percent	registry:outcomes
ACHIEVE-5	A4	ORFO_PO_36MG_QD	40	arm, responders			69 / 136	count_from_percent	registry:outcomes

Rerun this analysis yourself

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