Network meta-analysis

Systolic blood pressure change

Type 2 diabetes (adults)

weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference

Randomized trials

Treatments

6,501

Participants

Trial arms

In plain language

Across 10 trials with 6,501 participants, 4 of 15 treatments had a clearly better result than placebo on systolic blood pressure change, and for 11 the evidence could not tell them apart from placebo. The most favorable estimate was for retatrutide 12 mg subcutaneous once weekly: mean difference -11.94 mmHg (95% credible interval -18.56 to -5.24).

Retatrutide 12 mg subcutaneous once weekly: among the most effective (certainty pending).
Orforglipron 36 mg oral once daily: better than placebo but not among the most effective (certainty pending).
Orforglipron 12 mg oral once daily: better than placebo but not among the most effective (certainty pending).
Dulaglutide 4.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Retatrutide 0.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Semaglutide 1.0 mg subcutaneous once weekly: better than placebo but not among the most effective (certainty pending).
Dulaglutide 3.0 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Dulaglutide 1.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Orforglipron 3 mg oral once daily: not convincingly different from placebo (certainty pending).
Semaglutide 14 mg oral once daily (original tablet): not convincingly different from placebo (certainty pending).
Semaglutide 0.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Semaglutide 7 mg oral once daily (original tablet): not convincingly different from placebo (certainty pending).
Exenatide extended release 2 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
Additional oad: not convincingly different from placebo (certainty pending).
Insulin aspart (prandial): not convincingly different from placebo (certainty pending).

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 mmHg. 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	Confidence
Retatrutide 12 mg subcutaneous once weekly RETA_SC_12MG_QW	-11.94 (-18.56 to -5.24)	-19.08 to -4.69	-12.19 (-18.40 to -5.98)	Better	pending
Orforglipron 36 mg oral once daily ORFO_PO_36MG_QD	-4.50 (-6.98 to -1.58)	-8.09 to -0.49	-4.50 (-6.57 to -2.44)	Better	pending
Orforglipron 12 mg oral once daily ORFO_PO_12MG_QD	-4.19 (-6.64 to -1.61)	-8.05 to -0.27	-4.22 (-6.27 to -2.16)	Better	pending
Dulaglutide 4.5 mg subcutaneous once weekly DULA_SC_4p5MG_QW	-3.53 (-10.50 to 3.30)	-10.99 to 3.57	-3.73 (-10.06 to 2.60)	Unclear	pending
Retatrutide 0.5 mg subcutaneous once weekly RETA_SC_0p5MG_QW	-3.29 (-9.47 to 2.96)	-10.09 to 3.52	-3.42 (-9.29 to 2.45)	Unclear	pending
Semaglutide 1.0 mg subcutaneous once weekly SEMA_SC_1p0MG_QW	-3.23 (-6.34 to -0.14)	-7.49 to 0.91	-3.21 (-5.86 to -0.55)	Better	pending
Dulaglutide 3.0 mg subcutaneous once weekly DULA_SC_3p0MG_QW	-3.00 (-9.97 to 3.82)	-10.60 to 4.43	-3.23 (-9.56 to 3.10)	Unclear	pending
Dulaglutide 1.5 mg subcutaneous once weekly DULA_SC_1p5MG_QW	-2.62 (-8.91 to 3.60)	-9.52 to 4.03	-2.83 (-8.82 to 3.16)	Unclear	pending
Orforglipron 3 mg oral once daily ORFO_PO_3MG_QD	-2.39 (-4.84 to 0.38)	-6.22 to 1.46	-2.38 (-4.49 to -0.27)	Unclear	pending
Semaglutide 14 mg oral once daily (original tablet) SEMA_PO_14MG_QD	-2.10 (-5.63 to 1.92)	-6.55 to 2.89	-2.14 (-4.83 to 0.56)	Unclear	pending
Semaglutide 0.5 mg subcutaneous once weekly SEMA_SC_0p5MG_QW	-1.54 (-6.34 to 3.12)	-7.29 to 3.86	-1.51 (-5.27 to 2.25)	Unclear	pending
Semaglutide 7 mg oral once daily (original tablet) SEMA_PO_7MG_QD	-1.42 (-4.84 to 2.36)	-5.79 to 3.52	-1.44 (-4.13 to 1.25)	Unclear	pending
Exenatide extended release 2 mg subcutaneous once weekly EXENER_SC_2MG_QW	-0.85 (-5.40 to 3.74)	-6.14 to 4.43	-0.84 (-4.42 to 2.75)	Unclear	pending
Additional oad OTHER_ACTIVE_additional_OAD	0.65 (-4.37 to 5.53)	-5.04 to 6.06	0.69 (-3.35 to 4.73)	Unclear	pending
Insulin aspart (prandial) INS_ASPART	0.69 (-3.76 to 5.09)	-4.62 to 5.81	0.69 (-2.55 to 3.94)	Unclear	pending

Confidence in the results

How much each comparison can be trusted, rated with CINeMA in six domains and summarized with GRADE.

Ratings follow the protocol's numeric rules from risk of bias and indirectness judgments made by language model reviewers (amendment A028); no human has verified them yet. Reporting bias (ROB-MEN): some concerns.

Confidence in each comparison with Placebo
Comparison	Within study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence
Dulaglutide 1.5 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Placebo	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Placebo	pending	some	pending	some	none	some	pending
Orforglipron 12 mg oral once daily versus Placebo	pending	some	pending	some	none	some	pending
Orforglipron 36 mg oral once daily versus Placebo	pending	some	pending	some	none	some	pending
Additional oad versus Placebo	pending	some	pending	major	none	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Retatrutide 12 mg subcutaneous once weekly versus Placebo	pending	some	pending	none	none	some	pending
Semaglutide 7 mg oral once daily (original tablet) versus Placebo	pending	some	pending	major	none	some	pending
Semaglutide 14 mg oral once daily (original tablet) versus Placebo	pending	some	pending	some	some	some	pending
Semaglutide 0.5 mg subcutaneous once weekly versus Placebo	pending	some	pending	major	none	some	pending
Semaglutide 1.0 mg subcutaneous once weekly versus Placebo	pending	some	pending	some	none	some	pending

Every other comparison (105)

Confidence in the other comparisons
Comparison	Within study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence
Dulaglutide 1.5 mg subcutaneous once weekly versus Dulaglutide 3.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Dulaglutide 4.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Dulaglutide 4.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Exenatide extended release 2 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Exenatide extended release 2 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Exenatide extended release 2 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Insulin aspart (prandial)	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Insulin aspart (prandial)	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Insulin aspart (prandial)	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Insulin aspart (prandial)	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Orforglipron 3 mg oral once daily	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Orforglipron 3 mg oral once daily	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Orforglipron 3 mg oral once daily	pending	some	pending	some	some	some	pending
Orforglipron 36 mg oral once daily versus Orforglipron 3 mg oral once daily	pending	some	pending	some	some	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Orforglipron 12 mg oral once daily	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Orforglipron 12 mg oral once daily	pending	some	pending	some	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Orforglipron 36 mg oral once daily	pending	some	pending	some	some	some	pending
Insulin aspart (prandial) versus Orforglipron 36 mg oral once daily	pending	some	pending	some	none	some	pending
Orforglipron 12 mg oral once daily versus Orforglipron 36 mg oral once daily	pending	some	pending	some	some	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Additional oad	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Additional oad	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Additional oad	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Additional oad	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Additional oad	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Additional oad	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Additional oad	pending	some	pending	some	none	some	pending
Orforglipron 36 mg oral once daily versus Additional oad	pending	some	pending	some	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 36 mg oral once daily versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Additional oad versus Retatrutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	none	some	pending
Insulin aspart (prandial) versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	none	some	pending
Orforglipron 3 mg oral once daily versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	some	some	pending
Orforglipron 12 mg oral once daily versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Orforglipron 36 mg oral once daily versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Additional oad versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	none	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Retatrutide 12 mg subcutaneous once weekly	pending	some	pending	none	some	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	some	none	some	pending
Orforglipron 36 mg oral once daily versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	some	none	some	pending
Additional oad versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Retatrutide 12 mg subcutaneous once weekly versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	none	none	some	pending
Semaglutide 14 mg oral once daily (original tablet) versus Semaglutide 7 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	some	none	some	pending
Orforglipron 36 mg oral once daily versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	some	none	some	pending
Additional oad versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	major	none	some	pending
Retatrutide 12 mg subcutaneous once weekly versus Semaglutide 14 mg oral once daily (original tablet)	pending	some	pending	none	some	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Insulin aspart (prandial) versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 3 mg oral once daily versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 36 mg oral once daily versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Additional oad versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	some	some	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Retatrutide 12 mg subcutaneous once weekly versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	none	some	some	pending
Semaglutide 7 mg oral once daily (original tablet) versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Semaglutide 14 mg oral once daily (original tablet) versus Semaglutide 0.5 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 1.5 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 3.0 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Dulaglutide 4.5 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Exenatide extended release 2 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	some	some	some	pending
Insulin aspart (prandial) versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Orforglipron 3 mg oral once daily versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 12 mg oral once daily versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Orforglipron 36 mg oral once daily versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Additional oad versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Retatrutide 0.5 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Retatrutide 12 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	some	none	some	pending
Semaglutide 7 mg oral once daily (original tablet) versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Semaglutide 14 mg oral once daily (original tablet) versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	major	none	some	pending
Semaglutide 0.5 mg subcutaneous once weekly versus Semaglutide 1.0 mg subcutaneous once weekly	pending	some	pending	some	some	some	pending

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.

Rank probabilities

Probability of each rank for each treatment
Treatment	Rank 1	Rank 2	Rank 3	Rank 4	Rank 5	Rank 6	Rank 7	Rank 8	Rank 9	Rank 10	Rank 11	Rank 12	Rank 13	Rank 14	Rank 15	Rank 16	Mean rank
RETA_SC_12MG_QW	96%	2%	1%	1%													1.1
ORFO_PO_36MG_QD	1%	25%	20%	12%	11%	12%	9%	4%	2%	1%	1%						4.4
ORFO_PO_12MG_QD	1%	13%	23%	15%	11%	13%	11%	6%	4%	2%	1%						4.9
SEMA_SC_1p0MG_QW		7%	8%	11%	12%	12%	12%	13%	9%	7%	6%	2%	1%				6.5
DULA_SC_4p5MG_QW	1%	18%	13%	11%	8%	6%	6%	5%	6%	5%	4%	4%	4%	4%	3%	2%	6.7
RETA_SC_0p5MG_QW		19%	7%	7%	10%	7%	7%	6%	5%	6%	5%	5%	5%	4%	3%	4%	7.2
DULA_SC_3p0MG_QW		8%	13%	10%	8%	7%	7%	7%	6%	6%	5%	5%	4%	4%	5%	4%	7.7
ORFO_PO_3MG_QD		1%	1%	6%	8%	9%	11%	14%	14%	13%	10%	6%	4%	2%	1%		8.5
DULA_SC_1p5MG_QW		3%	7%	12%	10%	8%	7%	7%	7%	6%	6%	6%	6%	6%	5%	5%	8.6
SEMA_PO_14MG_QD		1%	2%	6%	7%	8%	9%	11%	13%	11%	10%	8%	6%	4%	3%	2%	9.0
SEMA_SC_0p5MG_QW		3%	3%	4%	5%	6%	6%	8%	9%	9%	9%	11%	11%	9%	5%	2%	9.7
SEMA_PO_7MG_QD			1%	2%	4%	5%	6%	8%	10%	12%	13%	11%	9%	7%	6%	5%	10.4
EXENER_SC_2MG_QW		1%	1%	2%	3%	4%	5%	6%	7%	9%	10%	12%	14%	12%	9%	6%	11.1
PLACEBO							1%	1%	3%	5%	9%	16%	19%	20%	16%	10%	13.1
OTHER_ACTIVE_additional_OAD			1%	1%	1%	2%	2%	2%	3%	4%	5%	7%	9%	13%	18%	32%	13.4
INS_ASPART					1%	1%	1%	2%	3%	3%	5%	7%	9%	14%	25%	28%	13.7

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	RETA_SC_12MG_QW	ORFO_PO_36MG_QD	ORFO_PO_12MG_QD	DULA_SC_4p5MG_QW	RETA_SC_0p5MG_QW	SEMA_SC_1p0MG_QW	DULA_SC_3p0MG_QW	DULA_SC_1p5MG_QW	ORFO_PO_3MG_QD	SEMA_PO_14MG_QD	SEMA_SC_0p5MG_QW	SEMA_PO_7MG_QD	EXENER_SC_2MG_QW	OTHER_ACTIVE_additional_OAD	INS_ASPART
PLACEBO	PLACEBO	11.94 5.24 to 18.56	4.50 1.58 to 6.98	4.19 1.61 to 6.64	3.53 -3.30 to 10.50	3.29 -2.96 to 9.47	3.23 0.14 to 6.34	3.00 -3.82 to 9.97	2.62 -3.60 to 8.91	2.39 -0.38 to 4.84	2.10 -1.92 to 5.63	1.54 -3.12 to 6.34	1.42 -2.36 to 4.84	0.85 -3.74 to 5.40	-0.65 -5.53 to 4.37	-0.69 -5.09 to 3.76
RETA_SC_12MG_QW	-11.94 -18.56 to -5.24	RETA_SC_12MG_QW	-7.46 -14.62 to -0.43	-7.75 -14.91 to -0.60	-8.41 -15.37 to -1.22	-8.68 -14.81 to -2.29	-8.64 -16.02 to -1.45	-8.87 -15.87 to -1.77	-9.31 -15.62 to -2.75	-9.58 -16.69 to -2.38	-9.85 -17.47 to -2.31	-10.33 -18.41 to -2.23	-10.48 -18.21 to -3.14	-11.04 -19.00 to -2.94	-12.49 -20.75 to -4.38	-12.58 -20.37 to -4.64
ORFO_PO_36MG_QD	-4.50 -6.98 to -1.58	7.46 0.43 to 14.62	ORFO_PO_36MG_QD	-0.29 -2.22 to 1.96	-1.01 -8.18 to 6.86	-1.22 -7.94 to 5.69	-1.27 -5.13 to 3.01	-1.50 -8.63 to 6.23	-1.88 -8.48 to 5.15	-2.11 -4.53 to 0.63	-2.38 -5.55 to 0.66	-2.95 -8.13 to 2.71	-3.08 -6.11 to -0.05	-3.62 -8.71 to 1.84	-5.14 -10.47 to 0.75	-5.16 -10.00 to 0.19
ORFO_PO_12MG_QD	-4.19 -6.64 to -1.61	7.75 0.60 to 14.91	0.29 -1.96 to 2.22	ORFO_PO_12MG_QD	-0.69 -7.94 to 6.81	-0.87 -7.61 to 5.87	-0.98 -4.81 to 3.08	-1.17 -8.45 to 6.26	-1.60 -8.32 to 5.22	-1.80 -4.43 to 0.68	-2.08 -5.26 to 0.68	-2.61 -8.01 to 2.69	-2.79 -5.90 to 0.04	-3.33 -8.51 to 2.00	-4.85 -10.27 to 0.84	-4.89 -9.77 to 0.30
DULA_SC_4p5MG_QW	-3.53 -10.50 to 3.30	8.41 1.22 to 15.37	1.01 -6.86 to 8.18	0.69 -6.81 to 7.94	DULA_SC_4p5MG_QW	-0.24 -7.04 to 6.72	-0.26 -7.93 to 7.12	-0.50 -3.41 to 2.59	-0.91 -3.96 to 2.28	-1.13 -8.71 to 6.00	-1.41 -9.65 to 6.14	-1.99 -10.44 to 6.34	-2.08 -10.22 to 5.50	-2.68 -10.85 to 5.55	-4.24 -12.57 to 4.19	-4.19 -12.16 to 3.81
RETA_SC_0p5MG_QW	-3.29 -9.47 to 2.96	8.68 2.29 to 14.81	1.22 -5.69 to 7.94	0.87 -5.87 to 7.61	0.24 -6.72 to 7.04	RETA_SC_0p5MG_QW	-0.04 -7.02 to 6.86	-0.25 -7.07 to 6.47	-0.63 -6.82 to 5.46	-0.91 -7.69 to 5.62	-1.21 -8.58 to 5.76	-1.73 -9.54 to 6.21	-1.85 -9.14 to 5.07	-2.39 -10.24 to 5.08	-3.93 -11.70 to 4.03	-3.95 -11.45 to 3.70
SEMA_SC_1p0MG_QW	-3.23 -6.34 to -0.14	8.64 1.45 to 16.02	1.27 -3.01 to 5.13	0.98 -3.08 to 4.81	0.26 -7.12 to 7.93	0.04 -6.86 to 7.02	SEMA_SC_1p0MG_QW	-0.25 -7.74 to 7.25	-0.62 -7.53 to 6.37	-0.86 -4.94 to 3.14	-1.10 -6.22 to 3.45	-1.68 -5.26 to 1.88	-1.79 -6.90 to 2.66	-2.37 -5.90 to 1.10	-3.86 -7.62 to -0.10	-3.89 -7.01 to -0.81
DULA_SC_3p0MG_QW	-3.00 -9.97 to 3.82	8.87 1.77 to 15.87	1.50 -6.23 to 8.63	1.17 -6.26 to 8.45	0.50 -2.59 to 3.41	0.25 -6.47 to 7.07	0.25 -7.25 to 7.74	DULA_SC_3p0MG_QW	-0.41 -3.56 to 2.76	-0.61 -8.09 to 6.56	-0.92 -9.09 to 6.61	-1.46 -9.89 to 6.96	-1.62 -9.63 to 5.97	-2.18 -10.38 to 5.97	-3.70 -12.09 to 4.87	-3.69 -11.73 to 4.37
DULA_SC_1p5MG_QW	-2.62 -8.91 to 3.60	9.31 2.75 to 15.62	1.88 -5.15 to 8.48	1.60 -5.22 to 8.32	0.91 -2.28 to 3.96	0.63 -5.46 to 6.82	0.62 -6.37 to 7.53	0.41 -2.76 to 3.56	DULA_SC_1p5MG_QW	-0.24 -7.10 to 6.50	-0.47 -8.07 to 6.63	-1.05 -9.08 to 6.81	-1.21 -8.57 to 5.83	-1.79 -9.46 to 5.79	-3.30 -11.15 to 4.67	-3.27 -10.78 to 4.18
ORFO_PO_3MG_QD	-2.39 -4.84 to 0.38	9.58 2.38 to 16.69	2.11 -0.63 to 4.53	1.80 -0.68 to 4.43	1.13 -6.00 to 8.71	0.91 -5.62 to 7.69	0.86 -3.14 to 4.94	0.61 -6.56 to 8.09	0.24 -6.50 to 7.10	ORFO_PO_3MG_QD	-0.27 -4.07 to 3.33	-0.84 -6.12 to 4.61	-0.98 -4.77 to 2.55	-1.51 -6.62 to 3.73	-3.03 -8.56 to 2.81	-3.09 -8.01 to 2.21
SEMA_PO_14MG_QD	-2.10 -5.63 to 1.92	9.85 2.31 to 17.47	2.38 -0.66 to 5.55	2.08 -0.68 to 5.26	1.41 -6.14 to 9.65	1.21 -5.76 to 8.58	1.10 -3.45 to 6.22	0.92 -6.61 to 9.09	0.47 -6.63 to 8.07	0.27 -3.33 to 4.07	SEMA_PO_14MG_QD	-0.56 -6.37 to 5.74	-0.68 -3.97 to 2.64	-1.26 -6.88 to 4.92	-2.76 -8.58 to 3.83	-2.79 -8.28 to 3.19
SEMA_SC_0p5MG_QW	-1.54 -6.34 to 3.12	10.33 2.23 to 18.41	2.95 -2.71 to 8.13	2.61 -2.69 to 8.01	1.99 -6.34 to 10.44	1.73 -6.21 to 9.54	1.68 -1.88 to 5.26	1.46 -6.96 to 9.89	1.05 -6.81 to 9.08	0.84 -4.61 to 6.12	0.56 -5.74 to 6.37	SEMA_SC_0p5MG_QW	-0.15 -6.35 to 5.54	-0.67 -5.62 to 4.11	-2.23 -6.10 to 1.68	-2.24 -6.96 to 2.53
SEMA_PO_7MG_QD	-1.42 -4.84 to 2.36	10.48 3.14 to 18.21	3.08 0.05 to 6.11	2.79 -0.04 to 5.90	2.08 -5.50 to 10.22	1.85 -5.07 to 9.14	1.79 -2.66 to 6.90	1.62 -5.97 to 9.63	1.21 -5.83 to 8.57	0.98 -2.55 to 4.77	0.68 -2.64 to 3.97	0.15 -5.54 to 6.35	SEMA_PO_7MG_QD	-0.56 -6.22 to 5.45	-2.07 -8.01 to 4.17	-2.09 -7.42 to 4.02
EXENER_SC_2MG_QW	-0.85 -5.40 to 3.74	11.04 2.94 to 19.00	3.62 -1.84 to 8.71	3.33 -2.00 to 8.51	2.68 -5.55 to 10.85	2.39 -5.08 to 10.24	2.37 -1.10 to 5.90	2.18 -5.97 to 10.38	1.79 -5.79 to 9.46	1.51 -3.73 to 6.62	1.26 -4.92 to 6.88	0.67 -4.11 to 5.62	0.56 -5.45 to 6.22	EXENER_SC_2MG_QW	-1.55 -6.64 to 3.69	-1.53 -6.05 to 3.31
OTHER_ACTIVE_additional_OAD	0.65 -4.37 to 5.53	12.49 4.38 to 20.75	5.14 -0.75 to 10.47	4.85 -0.84 to 10.27	4.24 -4.19 to 12.57	3.93 -4.03 to 11.70	3.86 0.10 to 7.62	3.70 -4.87 to 12.09	3.30 -4.67 to 11.15	3.03 -2.81 to 8.56	2.76 -3.83 to 8.58	2.23 -1.68 to 6.10	2.07 -4.17 to 8.01	1.55 -3.69 to 6.64	OTHER_ACTIVE_additional_OAD	-0.03 -4.83 to 4.81
INS_ASPART	0.69 -3.76 to 5.09	12.58 4.64 to 20.37	5.16 -0.19 to 10.00	4.89 -0.30 to 9.77	4.19 -3.81 to 12.16	3.95 -3.70 to 11.45	3.89 0.81 to 7.01	3.69 -4.37 to 11.73	3.27 -4.18 to 10.78	3.09 -2.21 to 8.01	2.79 -3.19 to 8.28	2.24 -2.53 to 6.96	2.09 -4.02 to 7.42	1.53 -3.31 to 6.05	0.03 -4.81 to 4.83	INS_ASPART

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.851 (95% CrI 0.045 to 3.240)
Residual deviance: 26.8 for 28 data points
DIC: 51.6 (pD 24.8)
Largest R-hat: 1.002
Smallest ESS: bulk 1,425, tail 1,956
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 60^2); PR03 N(0, 30^2); PR07 half normal(0, 6^2) on tau

Frequentist check (netmeta)

Method: inverse variance, REML, MD
Tau: 0.753
I squared: 0%
Q (total): 4.15 on 5 df, P = 0.528
Q (between designs): 0.84, P = 0.360

Inconsistency

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

Frequentist node splitting (Back-calculation). A small P value means direct and indirect evidence disagree.
Comparison	Trials	Direct	Indirect	Network	P
Orforglipron 12 mg oral once daily versus Orforglipron 36 mg oral once daily ORFO_PO_12MG_QD:ORFO_PO_36MG_QD	3	0.24 -1.36 to 1.85	34.45 -11.09 to 79.99	0.29 -1.32 to 1.89	0.141
Orforglipron 12 mg oral once daily versus Orforglipron 3 mg oral once daily ORFO_PO_12MG_QD:ORFO_PO_3MG_QD	2	-2.16 -4.36 to 0.04	0.16 -5.29 to 5.61	-1.84 -3.88 to 0.20	0.439
Orforglipron 12 mg oral once daily versus Placebo ORFO_PO_12MG_QD:PLACEBO	2	-4.54 -6.76 to -2.33	-2.17 -7.72 to 3.38	-4.22 -6.27 to -2.16	0.436
Orforglipron 12 mg oral once daily versus Semaglutide 14 mg oral once daily (original tablet) ORFO_PO_12MG_QD:SEMA_PO_14MG_QD	1	-1.80 -3.96 to 0.36	-4.45 -10.75 to 1.85	-2.08 -4.12 to -0.03	0.436
Orforglipron 12 mg oral once daily versus Semaglutide 7 mg oral once daily (original tablet) ORFO_PO_12MG_QD:SEMA_PO_7MG_QD	1	-2.50 -4.65 to -0.35	-5.12 -11.36 to 1.12	-2.78 -4.81 to -0.74	0.436
Orforglipron 36 mg oral once daily versus Orforglipron 3 mg oral once daily ORFO_PO_36MG_QD:ORFO_PO_3MG_QD	2	-1.74 -3.96 to 0.48	-4.27 -9.55 to 1.02	-2.12 -4.17 to -0.08	0.388
Orforglipron 36 mg oral once daily versus Placebo ORFO_PO_36MG_QD:PLACEBO	2	-4.17 -6.40 to -1.94	-6.48 -11.92 to -1.03	-4.50 -6.57 to -2.44	0.442
Orforglipron 36 mg oral once daily versus Semaglutide 14 mg oral once daily (original tablet) ORFO_PO_36MG_QD:SEMA_PO_14MG_QD	1	-2.70 -4.97 to -0.43	-0.28 -5.92 to 5.35	-2.36 -4.47 to -0.26	0.436
Orforglipron 36 mg oral once daily versus Semaglutide 7 mg oral once daily (original tablet) ORFO_PO_36MG_QD:SEMA_PO_7MG_QD	1	-3.40 -5.66 to -1.14	-1.01 -6.59 to 4.58	-3.06 -5.16 to -0.97	0.436
Orforglipron 3 mg oral once daily versus Placebo ORFO_PO_3MG_QD:PLACEBO	2	-2.33 -4.44 to -0.21	-52.13 -118 to 14.18	-2.38 -4.49 to -0.27	0.141

Heterogeneity within designs (decomp.design)
Design	Q	df	P
PLACEBO:SEMA_SC_1p0MG_QW	0.10	1	0.752
PLACEBO:ORFO_PO_12MG_QD:ORFO_PO_36MG_QD:ORFO_PO_3MG_QD	3.22	3	0.360

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.

Comparisons ordered as DULA_SC_1p5MG_QW, DULA_SC_3p0MG_QW, DULA_SC_4p5MG_QW, EXENER_SC_2MG_QW, INS_ASPART, ORFO_PO_12MG_QD, ORFO_PO_36MG_QD, ORFO_PO_3MG_QD, OTHER_ACTIVE_additional_OAD, RETA_SC_0p5MG_QW, RETA_SC_12MG_QW, SEMA_PO_14MG_QD, SEMA_PO_7MG_QD, SEMA_SC_0p5MG_QW, SEMA_SC_1p0MG_QW, PLACEBO; the shaded triangle is where 95% of points would fall without small study effects. Egger type test P = 0.946.

Contribution of direct evidence

Percent contribution of each direct comparison (columns) to each network estimate (rows), from netcontrib.

Contribution of direct comparisons to network estimates
Network estimate	DULA_SC_1p5MG_QW:DULA_SC_3p0MG_QW:DULA_SC_4p5MG_QW	DULA_SC_1p5MG_QW:PLACEBO:RETA_SC_0p5MG_QW:RETA_SC_12MG_QW	EXENER_SC_2MG_QW:SEMA_SC_1p0MG_QW	INS_ASPART:SEMA_SC_1p0MG_QW	ORFO_PO_12MG_QD:ORFO_PO_36MG_QD:ORFO_PO_3MG_QD:PLACEBO	ORFO_PO_12MG_QD:ORFO_PO_36MG_QD:SEMA_PO_14MG_QD:SEMA_PO_7MG_QD	OTHER_ACTIVE_additional_OAD:SEMA_SC_0p5MG_QW:SEMA_SC_1p0MG_QW	PLACEBO:SEMA_SC_1p0MG_QW
DULA_SC_1p5MG_QW:PLACEBO		100
DULA_SC_3p0MG_QW:PLACEBO	47	53
DULA_SC_4p5MG_QW:PLACEBO	47	53
EXENER_SC_2MG_QW:PLACEBO			50					50
INS_ASPART:PLACEBO				50				50
ORFO_PO_12MG_QD:PLACEBO					86	14
ORFO_PO_36MG_QD:PLACEBO					86	15
ORFO_PO_3MG_QD:PLACEBO					100
OTHER_ACTIVE_additional_OAD:PLACEBO							56	44
PLACEBO:RETA_SC_0p5MG_QW		100
PLACEBO:RETA_SC_12MG_QW		100
PLACEBO:SEMA_PO_14MG_QD					50	50
PLACEBO:SEMA_PO_7MG_QD					50	50
PLACEBO:SEMA_SC_0p5MG_QW							54	46
PLACEBO:SEMA_SC_1p0MG_QW								100

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; 9 of 10
AWARD-11 S000046	34.23
SUSTAIN™ 3 S000329	33.8
SUSTAIN 11 S000363	31.55
REMODEL S000395	30.8
ACHIEVE-3 S000438	35.1
NCT04867785 S000489	35.08
ACHIEVE-5 S001044	30.8
STRIDE S001363	28.7 median
SUSTAIN™ S001498	26.38
ACHIEVE-1 S001950	body weight 90.2 kg

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 26.4 (OTHER_ACTIVE_additional_OAD vs SEMA_SC_0p5MG_QW vs SEMA_SC_1p0MG_QW) to 35.1 (ORFO_PO_12MG_QD vs ORFO_PO_36MG_QD vs SEMA_PO_14MG_QD vs SEMA_PO_7MG_QD) kg/m2; threshold 3
NoteOutcome assessment, time point: selected time points span 36 to 56 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 3, modified_itt 4, randomized 2, safety 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 8, not stated 2
NoteRisk of bias, blinding: mixed: double_blind 6, open_label 4
NoteData handling, input conversions: n_randomized 6

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
AWARD-11	52	safety	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2018	age 18 or older; HbA1c 7.5 to 11.0%; BMI 25 or more; metformin 1500 mg/day or more; GLP-1 RA and insulin naive
SUSTAIN™ 3	56	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2013	age 18 or older; T2D on stable 1 to 2 oral drugs; HbA1c 7.0 to 10.5 percent; eGFR 60 or more
SUSTAIN 11	52	full_analysis	not stated	not stated	not stated	not stated	hypothetical	not stated	open_label	industry	2018	adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin
REMODEL	52	randomized	not stated	not stated	not stated	not stated	hypothetical	not stated	double_blind	industry	2021	T2D with HbA1c 9.0 percent or less; eGFR 30 to 75; UACR 20 to under 5000 mg/g
ACHIEVE-3	52	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2023	adults T2D on metformin; HbA1c 7.0 to 10.5 percent
NCT04867785	36	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2021	age 18 to 75; HbA1c 7.0 to 10.5 percent; BMI 25 to 50; diet and exercise or stable metformin
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
STRIDE	52	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2020	age 18 or more; type 2 diabetes; symptomatic PAD Fontaine IIa; ABI 0.90 or less or TBI 0.70 or less
SUSTAIN™	56	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2014	Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more
ACHIEVE-1	40	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2023	adults with type 2 diabetes on diet and exercise alone; HbA1c 7.0 to 9.5 percent

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
AWARD-11	A1	DULA_SC_1p5MG_QW	52	arm, change	-3.200	0.500	612	n_randomized	R0021508:Table 2
AWARD-11	A2	DULA_SC_3p0MG_QW	52	arm, change	-3.600	0.500	616	n_randomized	R0021508:Table 2
AWARD-11	A3	DULA_SC_4p5MG_QW	52	arm, change	-4.100	0.500	614	n_randomized	R0021508:Table 2
SUSTAIN™ 3	A1	SEMA_SC_1p0MG_QW	56	arm, change	-4.600	0.680	404		registry:outcomes
SUSTAIN™ 3	A2	EXENER_SC_2MG_QW	56	arm, change	-2.230	0.700	405		registry:outcomes
SUSTAIN 11	A1	SEMA_SC_1p0MG_QW	52	contrast, md	-3.900	0.587			R0022346:Results
SUSTAIN 11	A2	INS_ASPART	52	contrast, md					R0022346:Results
REMODEL	A1	SEMA_SC_1p0MG_QW	52	contrast, md	-4.000	2.883			R0007381:Extended Data Table 2
REMODEL	A2	PLACEBO	52	contrast, md					R0007381:Extended Data Table 2
ACHIEVE-3	A1	ORFO_PO_12MG_QD	52	arm, change	-4.500	0.550	331		registry:outcomes
ACHIEVE-3	A2	ORFO_PO_36MG_QD	52	arm, change	-5.400	0.650	323		registry:outcomes
ACHIEVE-3	A3	SEMA_PO_7MG_QD	52	arm, change	-2.000	0.580	325		registry:outcomes
ACHIEVE-3	A4	SEMA_PO_14MG_QD	52	arm, change	-2.700	0.590	356		registry:outcomes
NCT04867785	A1	PLACEBO	36	arm, change	0.970	2.170	45		R0013029:Supplement Table S4
NCT04867785	A2	DULA_SC_1p5MG_QW	36	arm, change	-1.860	2.020	46		R0013029:Supplement Table S4
NCT04867785	A3	RETA_SC_0p5MG_QW	36	arm, change	-2.450	1.920	46		R0013029:Supplement Table S4
NCT04867785	A8	RETA_SC_12MG_QW	36	arm, change	-11.220	2.180	43		R0013029:Supplement Table S4
ACHIEVE-5	A1	PLACEBO	40	arm, change	0.000	1.030	141		registry:outcomes
ACHIEVE-5	A2	ORFO_PO_3MG_QD	40	arm, change	-1.900	0.940	137		registry:outcomes
ACHIEVE-5	A3	ORFO_PO_12MG_QD	40	arm, change	-3.200	1.130	132		registry:outcomes
ACHIEVE-5	A4	ORFO_PO_36MG_QD	40	arm, change	-2.200	1.260	136		registry:outcomes
STRIDE	A1	SEMA_SC_1p0MG_QW	52	arm, change	-4.000	0.852	310		registry:outcomes
STRIDE	A2	PLACEBO	52	arm, change	-1.000	1.008	319		registry:outcomes
SUSTAIN™	A1	SEMA_SC_0p5MG_QW	56	arm, change	-2.000	0.800	239	n_randomized	R0025024:Table 3
SUSTAIN™	A2	SEMA_SC_1p0MG_QW	56	arm, change	-3.700	0.800	241	n_randomized	R0025024:Table 3
SUSTAIN™	A3	OTHER_ACTIVE_additional_OAD	56	arm, change	0.200	1.100	121	n_randomized	R0025024:Table 3
ACHIEVE-1	A1	PLACEBO	40	arm, change	-0.500	0.880	138		registry:outcomes
ACHIEVE-1	A2	ORFO_PO_3MG_QD	40	arm, change	-3.200	0.910	143		registry:outcomes
ACHIEVE-1	A3	ORFO_PO_12MG_QD	40	arm, change	-6.100	0.970	137		registry:outcomes
ACHIEVE-1	A4	ORFO_PO_36MG_QD	40	arm, change	-6.000	0.910	141		registry:outcomes

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