Network meta-analysis

HbA1c change

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

weeks 20 to 36 (target week 26)Hypothetical (as if everyone stayed on treatment)Doses of a drug pooledMean difference

Randomized trials

Treatments

16,753

Participants

Trial arms

In plain language

Across 25 trials with 16,753 participants, 13 of 17 treatments had a clearly better result than placebo on HbA1c change, and for 4 the evidence could not tell them apart from placebo. The most favorable estimate was for tirzepatide injection: mean difference -1.61 percentage points (95% credible interval -1.99 to -1.22).

Tirzepatide injection: among the most effective (certainty pending).
Exenatide extended release and dapagliflozin injection: better than placebo but not among the most effective (certainty pending).
Semaglutide injection: among the most effective (certainty pending).
Insulin glargine with lixisenatide injection: among the most effective (certainty pending).
Dulaglutide injection: among the most effective (certainty pending).
Semaglutide tablet: among the most effective (certainty pending).
Safiglipron (HRS-7535) tablet: not convincingly different from placebo (certainty pending).
Liraglutide injection: among the most effective (certainty pending).
Exenatide extended release injection: better than placebo but not among the most effective (certainty pending).
Insulin degludec: better than placebo but not among the most effective (certainty pending).
Insulin glargine: better than placebo but not among the most effective (certainty pending).
Dapagliflozin: not convincingly different from placebo (certainty pending).
Visepegenatide injection: better than placebo but not among the most effective (certainty pending).
Exenatide injection: better than placebo but not among the most effective (certainty pending).
Sitagliptin: better than placebo but not among the most effective (certainty pending).
Empagliflozin: not convincingly different from placebo (certainty pending).
Lixisenatide injection: 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 percentage points. 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
Tirzepatide injection TIRZ_SC	-1.61 (-1.99 to -1.22)	-2.24 to -1.00	-1.63 (-1.98 to -1.28)	Better	pending
Exenatide extended release and dapagliflozin injection DAPAEXEN_SC	-1.29 (-2.14 to -0.40)	-2.27 to -0.28	-1.39 (-2.23 to -0.55)	Better	pending
Semaglutide injection SEMA_SC	-1.25 (-1.59 to -0.91)	-1.85 to -0.66	-1.26 (-1.57 to -0.95)	Better	pending
Insulin glargine with lixisenatide injection IGLARLIXI_SC	-1.15 (-1.62 to -0.66)	-1.84 to -0.48	-1.16 (-1.58 to -0.73)	Better	pending
Dulaglutide injection DULA_SC	-1.06 (-1.31 to -0.82)	-1.62 to -0.51	-1.07 (-1.30 to -0.85)	Better	pending
Semaglutide tablet SEMA_PO	-1.03 (-1.35 to -0.72)	-1.60 to -0.46	-1.05 (-1.33 to -0.77)	Better	pending
Safiglipron (HRS-7535) tablet SAFIGL_PO	-1.00 (-1.96 to 0.03)	-2.09 to 0.14	-1.11 (-2.06 to -0.15)	Unclear	pending
Liraglutide injection LIRA_SC	-0.94 (-1.26 to -0.62)	-1.53 to -0.36	-0.94 (-1.22 to -0.66)	Better	pending
Exenatide extended release injection EXENER_SC	-0.93 (-1.61 to -0.23)	-1.76 to -0.04	-1.01 (-1.68 to -0.34)	Better	pending
Insulin degludec INS_DEGLUDEC	-0.87 (-1.49 to -0.20)	-1.66 to -0.05	-0.89 (-1.45 to -0.33)	Better	pending
Insulin glargine INS_GLARGINE	-0.72 (-1.12 to -0.34)	-1.35 to -0.11	-0.74 (-1.08 to -0.39)	Better	pending
Dapagliflozin DAPAGLIFLOZIN	-0.69 (-1.54 to 0.19)	-1.67 to 0.33	-0.80 (-1.64 to 0.04)	Unclear	pending
Visepegenatide injection VISEPE_SC	-0.57 (-1.06 to -0.07)	-1.25 to 0.13	-0.57 (-1.02 to -0.12)	Better	pending
Exenatide injection EXEN_SC	-0.56 (-1.00 to -0.12)	-1.22 to 0.10	-0.60 (-1.01 to -0.19)	Better	pending
Sitagliptin SITAGLIPTIN	-0.52 (-0.82 to -0.20)	-1.08 to 0.06	-0.53 (-0.82 to -0.24)	Better	pending
Empagliflozin EMPAGLIFLOZIN	-0.43 (-1.01 to 0.15)	-1.18 to 0.33	-0.45 (-0.98 to 0.08)	Unclear	pending
Lixisenatide injection LIXI_SC	-0.34 (-0.72 to 0.03)	-0.96 to 0.27	-0.35 (-0.68 to -0.02)	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
Exenatide extended release and dapagliflozin injection versus Placebo	pending	some	pending	none	some	some	pending
Dapagliflozin versus Placebo	pending	some	pending	some	some	some	pending
Dulaglutide injection versus Placebo	pending	some	pending	none	none	some	pending
Empagliflozin versus Placebo	pending	some	pending	some	some	some	pending
Exenatide injection versus Placebo	pending	some	pending	some	none	some	pending
Exenatide extended release injection versus Placebo	pending	some	pending	some	none	some	pending
Insulin glargine with lixisenatide injection versus Placebo	pending	some	pending	none	none	some	pending
Insulin degludec versus Placebo	pending	some	pending	some	none	some	pending
Insulin glargine versus Placebo	pending	some	pending	none	some	some	pending
Liraglutide injection versus Placebo	pending	some	pending	none	none	some	pending
Lixisenatide injection versus Placebo	pending	some	pending	some	none	some	pending
Safiglipron (HRS-7535) tablet versus Placebo	pending	some	pending	some	none	some	pending
Semaglutide tablet versus Placebo	pending	some	pending	none	none	some	pending
Semaglutide injection versus Placebo	pending	some	pending	none	none	some	pending
Sitagliptin versus Placebo	pending	some	pending	some	none	some	pending
Tirzepatide injection versus Placebo	pending	some	pending	none	none	some	pending
Visepegenatide injection versus Placebo	pending	some	pending	some	none	some	pending

Every other comparison (136)

Confidence in the other comparisons
Comparison	Within study bias	Reporting bias	Indirectness	Imprecision	Heterogeneity	Incoherence	Confidence
Exenatide extended release and dapagliflozin injection versus Dapagliflozin	pending	some	pending	some	none	some	pending
Exenatide extended release and dapagliflozin injection versus Dulaglutide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Dulaglutide injection	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Empagliflozin	pending	some	pending	some	some	some	pending
Dapagliflozin versus Empagliflozin	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Empagliflozin	pending	some	pending	some	none	some	pending
Exenatide extended release and dapagliflozin injection versus Exenatide injection	pending	some	pending	some	none	some	pending
Dapagliflozin versus Exenatide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Exenatide injection	pending	some	pending	some	none	some	pending
Empagliflozin versus Exenatide injection	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Exenatide extended release injection	pending	some	pending	some	some	some	pending
Dapagliflozin versus Exenatide extended release injection	pending	some	pending	some	some	some	pending
Dulaglutide injection versus Exenatide extended release injection	pending	some	pending	major	none	some	pending
Empagliflozin versus Exenatide extended release injection	pending	some	pending	major	none	some	pending
Exenatide injection versus Exenatide extended release injection	pending	some	pending	some	some	some	pending
Exenatide extended release and dapagliflozin injection versus Insulin glargine with lixisenatide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Insulin glargine with lixisenatide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Insulin glargine with lixisenatide injection	pending	some	pending	major	none	some	pending
Empagliflozin versus Insulin glargine with lixisenatide injection	pending	some	pending	some	none	some	pending
Exenatide injection versus Insulin glargine with lixisenatide injection	pending	some	pending	some	none	some	pending
Exenatide extended release injection versus Insulin glargine with lixisenatide injection	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Insulin degludec	pending	some	pending	major	none	some	pending
Dapagliflozin versus Insulin degludec	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Insulin degludec	pending	some	pending	major	none	some	pending
Empagliflozin versus Insulin degludec	pending	some	pending	major	none	some	pending
Exenatide injection versus Insulin degludec	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Insulin degludec	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Insulin degludec	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Insulin glargine	pending	some	pending	major	none	some	pending
Dapagliflozin versus Insulin glargine	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Insulin glargine	pending	some	pending	some	none	some	pending
Empagliflozin versus Insulin glargine	pending	some	pending	major	none	some	pending
Exenatide injection versus Insulin glargine	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Insulin glargine	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Insulin glargine	pending	some	pending	some	none	some	pending
Insulin degludec versus Insulin glargine	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Liraglutide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Liraglutide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Liraglutide injection	pending	some	pending	some	some	some	pending
Empagliflozin versus Liraglutide injection	pending	some	pending	some	none	some	pending
Exenatide injection versus Liraglutide injection	pending	some	pending	some	some	some	pending
Exenatide extended release injection versus Liraglutide injection	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Liraglutide injection	pending	some	pending	major	none	some	pending
Insulin degludec versus Liraglutide injection	pending	some	pending	major	none	some	pending
Insulin glargine versus Liraglutide injection	pending	some	pending	some	some	some	pending
Exenatide extended release and dapagliflozin injection versus Lixisenatide injection	pending	some	pending	some	none	some	pending
Dapagliflozin versus Lixisenatide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Lixisenatide injection	pending	some	pending	none	some	some	pending
Empagliflozin versus Lixisenatide injection	pending	some	pending	major	none	some	pending
Exenatide injection versus Lixisenatide injection	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Lixisenatide injection	pending	some	pending	some	some	some	pending
Insulin glargine with lixisenatide injection versus Lixisenatide injection	pending	some	pending	none	some	some	pending
Insulin degludec versus Lixisenatide injection	pending	some	pending	some	some	some	pending
Insulin glargine versus Lixisenatide injection	pending	some	pending	some	some	some	pending
Liraglutide injection versus Lixisenatide injection	pending	some	pending	some	none	some	pending
Exenatide extended release and dapagliflozin injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Dapagliflozin versus Safiglipron (HRS-7535) tablet	pending	some	pending	some	some	some	pending
Dulaglutide injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Empagliflozin versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Exenatide injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Insulin degludec versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Insulin glargine versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Liraglutide injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Lixisenatide injection versus Safiglipron (HRS-7535) tablet	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Dapagliflozin versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Empagliflozin versus Semaglutide tablet	pending	some	pending	some	none	some	pending
Exenatide injection versus Semaglutide tablet	pending	some	pending	some	none	some	pending
Exenatide extended release injection versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Insulin degludec versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Insulin glargine versus Semaglutide tablet	pending	some	pending	some	some	some	pending
Liraglutide injection versus Semaglutide tablet	pending	some	pending	some	some	some	pending
Lixisenatide injection versus Semaglutide tablet	pending	some	pending	some	none	some	pending
Safiglipron (HRS-7535) tablet versus Semaglutide tablet	pending	some	pending	major	none	some	pending
Exenatide extended release and dapagliflozin injection versus Semaglutide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Semaglutide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Semaglutide injection	pending	some	pending	some	some	some	pending
Empagliflozin versus Semaglutide injection	pending	some	pending	some	none	some	pending
Exenatide injection versus Semaglutide injection	pending	some	pending	some	none	some	pending
Exenatide extended release injection versus Semaglutide injection	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Semaglutide injection	pending	some	pending	major	none	some	pending
Insulin degludec versus Semaglutide injection	pending	some	pending	some	some	some	pending
Insulin glargine versus Semaglutide injection	pending	some	pending	some	none	some	pending
Liraglutide injection versus Semaglutide injection	pending	some	pending	some	some	some	pending
Lixisenatide injection versus Semaglutide injection	pending	some	pending	none	some	some	pending
Safiglipron (HRS-7535) tablet versus Semaglutide injection	pending	some	pending	major	none	some	pending
Semaglutide tablet versus Semaglutide injection	pending	some	pending	some	some	some	pending
Exenatide extended release and dapagliflozin injection versus Sitagliptin	pending	some	pending	some	some	some	pending
Dapagliflozin versus Sitagliptin	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Sitagliptin	pending	some	pending	some	none	some	pending
Empagliflozin versus Sitagliptin	pending	some	pending	major	none	some	pending
Exenatide injection versus Sitagliptin	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Sitagliptin	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Sitagliptin	pending	some	pending	some	none	some	pending
Insulin degludec versus Sitagliptin	pending	some	pending	major	none	some	pending
Insulin glargine versus Sitagliptin	pending	some	pending	some	some	some	pending
Liraglutide injection versus Sitagliptin	pending	some	pending	some	none	some	pending
Lixisenatide injection versus Sitagliptin	pending	some	pending	some	some	some	pending
Safiglipron (HRS-7535) tablet versus Sitagliptin	pending	some	pending	major	none	some	pending
Semaglutide tablet versus Sitagliptin	pending	some	pending	some	none	some	pending
Semaglutide injection versus Sitagliptin	pending	some	pending	none	some	some	pending
Exenatide extended release and dapagliflozin injection versus Tirzepatide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Dulaglutide injection versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Empagliflozin versus Tirzepatide injection	pending	some	pending	none	none	some	pending
Exenatide injection versus Tirzepatide injection	pending	some	pending	none	some	some	pending
Exenatide extended release injection versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Insulin glargine with lixisenatide injection versus Tirzepatide injection	pending	some	pending	some	some	some	pending
Insulin degludec versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Insulin glargine versus Tirzepatide injection	pending	some	pending	none	some	some	pending
Liraglutide injection versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Lixisenatide injection versus Tirzepatide injection	pending	some	pending	none	none	some	pending
Safiglipron (HRS-7535) tablet versus Tirzepatide injection	pending	some	pending	major	none	some	pending
Semaglutide tablet versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Semaglutide injection versus Tirzepatide injection	pending	some	pending	some	none	some	pending
Sitagliptin versus Tirzepatide injection	pending	some	pending	none	none	some	pending
Exenatide extended release and dapagliflozin injection versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Dapagliflozin versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Dulaglutide injection versus Visepegenatide injection	pending	some	pending	some	none	some	pending
Empagliflozin versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Exenatide injection versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Exenatide extended release injection versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Insulin glargine with lixisenatide injection versus Visepegenatide injection	pending	some	pending	some	none	some	pending
Insulin degludec versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Insulin glargine versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Liraglutide injection versus Visepegenatide injection	pending	some	pending	some	some	some	pending
Lixisenatide injection versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Safiglipron (HRS-7535) tablet versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Semaglutide tablet versus Visepegenatide injection	pending	some	pending	some	some	some	pending
Semaglutide injection versus Visepegenatide injection	pending	some	pending	some	none	some	pending
Sitagliptin versus Visepegenatide injection	pending	some	pending	major	none	some	pending
Tirzepatide injection versus Visepegenatide injection	pending	some	pending	none	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	Rank 17	Rank 18	Mean rank
TIRZ_SC	68%	19%	7%	3%	2%														1.5
SEMA_SC	2%	25%	24%	17%	11%	8%	6%	3%	2%	1%									4.0
DAPAEXEN_SC	20%	23%	13%	8%	6%	5%	5%	5%	4%	3%	2%	2%	1%	1%	1%				4.3
IGLARLIXI_SC	3%	13%	16%	14%	12%	11%	9%	7%	6%	4%	2%	1%	1%						5.3
DULA_SC		2%	6%	13%	18%	19%	17%	12%	7%	4%	1%								6.2
SEMA_PO		2%	7%	11%	15%	16%	14%	13%	10%	7%	4%	1%							6.6
SAFIGL_PO	6%	10%	10%	8%	6%	6%	6%	7%	7%	7%	6%	4%	4%	4%	3%	3%	3%	1%	7.6
LIRA_SC		1%	3%	5%	7%	11%	14%	15%	14%	12%	10%	5%	3%	1%					8.1
EXENER_SC		2%	6%	9%	9%	9%	8%	10%	11%	10%	8%	7%	5%	3%	2%	1%	1%		8.3
INS_DEGLUDEC		3%	5%	6%	6%	7%	8%	8%	9%	9%	9%	8%	6%	5%	4%	3%	2%		9.1
INS_GLARGINE				1%	1%	2%	5%	7%	10%	13%	15%	17%	13%	9%	5%	3%	1%		11.1
DAPAGLIFLOZIN			2%	4%	4%	4%	4%	5%	7%	8%	9%	9%	8%	7%	8%	8%	8%	4%	11.5
VISEPE_SC				1%	1%	1%	2%	4%	5%	6%	8%	11%	12%	13%	12%	11%	9%	1%	12.9
EXEN_SC						1%	1%	1%	3%	6%	10%	14%	17%	16%	14%	11%	6%	1%	13.2
SITAGLIPTIN								1%	3%	4%	7%	11%	15%	21%	21%	13%	3%		13.6
EMPAGLIFLOZIN						1%	1%	2%	3%	4%	5%	7%	9%	10%	14%	18%	20%	6%	14.3
LIXI_SC									1%	1%	2%	3%	5%	10%	15%	25%	34%	3%	15.5
PLACEBO															1%	3%	13%	83%	17.8

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	TIRZ_SC	DAPAEXEN_SC	SEMA_SC	IGLARLIXI_SC	DULA_SC	SEMA_PO	SAFIGL_PO	LIRA_SC	EXENER_SC	INS_DEGLUDEC	INS_GLARGINE	DAPAGLIFLOZIN	VISEPE_SC	EXEN_SC	SITAGLIPTIN	EMPAGLIFLOZIN	LIXI_SC
PLACEBO	PLACEBO	1.61 1.22 to 1.99	1.29 0.40 to 2.14	1.25 0.91 to 1.59	1.15 0.66 to 1.62	1.06 0.82 to 1.31	1.03 0.72 to 1.35	1.00 -0.03 to 1.96	0.94 0.62 to 1.26	0.93 0.23 to 1.61	0.87 0.20 to 1.49	0.72 0.34 to 1.12	0.69 -0.19 to 1.54	0.57 0.07 to 1.06	0.56 0.12 to 1.00	0.52 0.20 to 0.82	0.43 -0.15 to 1.01	0.34 -0.03 to 0.72
TIRZ_SC	-1.61 -1.99 to -1.22	TIRZ_SC	-0.32 -1.29 to 0.61	-0.36 -0.75 to 0.03	-0.46 -1.06 to 0.13	-0.55 -0.97 to -0.13	-0.57 -1.04 to -0.11	-0.61 -1.72 to 0.43	-0.67 -1.16 to -0.19	-0.68 -1.48 to 0.07	-0.74 -1.26 to -0.25	-0.89 -1.39 to -0.37	-0.91 -1.89 to 0.01	-1.04 -1.67 to -0.43	-1.05 -1.63 to -0.47	-1.09 -1.54 to -0.65	-1.18 -1.87 to -0.49	-1.27 -1.79 to -0.74
DAPAEXEN_SC	-1.29 -2.14 to -0.40	0.32 -0.61 to 1.29	DAPAEXEN_SC	-0.04 -0.95 to 0.94	-0.14 -1.09 to 0.86	-0.22 -1.08 to 0.69	-0.25 -1.15 to 0.66	-0.29 -1.05 to 0.46	-0.35 -1.26 to 0.59	-0.36 -0.90 to 0.19	-0.42 -1.50 to 0.67	-0.57 -1.44 to 0.39	-0.59 -1.14 to -0.05	-0.72 -1.72 to 0.31	-0.72 -1.49 to 0.07	-0.76 -1.66 to 0.16	-0.86 -1.89 to 0.20	-0.94 -1.87 to 0.00
SEMA_SC	-1.25 -1.59 to -0.91	0.36 -0.03 to 0.75	0.04 -0.94 to 0.95	SEMA_SC	-0.11 -0.69 to 0.46	-0.19 -0.58 to 0.21	-0.22 -0.63 to 0.18	-0.26 -1.35 to 0.77	-0.31 -0.75 to 0.12	-0.32 -1.12 to 0.41	-0.39 -1.03 to 0.24	-0.53 -1.02 to -0.02	-0.56 -1.53 to 0.36	-0.68 -1.28 to -0.10	-0.69 -1.25 to -0.14	-0.73 -1.09 to -0.37	-0.82 -1.47 to -0.18	-0.91 -1.38 to -0.42
IGLARLIXI_SC	-1.15 -1.62 to -0.66	0.46 -0.13 to 1.06	0.14 -0.86 to 1.09	0.11 -0.46 to 0.69	IGLARLIXI_SC	-0.08 -0.54 to 0.40	-0.11 -0.64 to 0.41	-0.16 -1.27 to 0.88	-0.21 -0.75 to 0.33	-0.21 -1.05 to 0.58	-0.28 -1.05 to 0.49	-0.42 -0.85 to 0.01	-0.45 -1.44 to 0.50	-0.57 -1.26 to 0.08	-0.58 -1.23 to 0.05	-0.62 -1.14 to -0.11	-0.71 -1.43 to -0.00	-0.81 -1.24 to -0.36
DULA_SC	-1.06 -1.31 to -0.82	0.55 0.13 to 0.97	0.22 -0.69 to 1.08	0.19 -0.21 to 0.58	0.08 -0.40 to 0.54	DULA_SC	-0.03 -0.38 to 0.30	-0.07 -1.11 to 0.91	-0.13 -0.51 to 0.25	-0.13 -0.84 to 0.55	-0.20 -0.87 to 0.45	-0.34 -0.67 to -0.01	-0.37 -1.27 to 0.47	-0.49 -1.06 to 0.05	-0.50 -0.95 to -0.06	-0.54 -0.91 to -0.19	-0.63 -1.23 to -0.02	-0.72 -1.13 to -0.31
SEMA_PO	-1.03 -1.35 to -0.72	0.57 0.11 to 1.04	0.25 -0.66 to 1.15	0.22 -0.18 to 0.63	0.11 -0.41 to 0.64	0.03 -0.30 to 0.38	SEMA_PO	-0.04 -1.09 to 0.97	-0.10 -0.45 to 0.25	-0.11 -0.86 to 0.63	-0.17 -0.86 to 0.50	-0.31 -0.76 to 0.15	-0.34 -1.26 to 0.53	-0.47 -1.05 to 0.12	-0.47 -0.99 to 0.04	-0.51 -0.80 to -0.23	-0.60 -1.11 to -0.10	-0.70 -1.11 to -0.25
SAFIGL_PO	-1.00 -1.96 to 0.03	0.61 -0.43 to 1.72	0.29 -0.46 to 1.05	0.26 -0.77 to 1.35	0.16 -0.88 to 1.27	0.07 -0.91 to 1.11	0.04 -0.97 to 1.09	SAFIGL_PO	-0.06 -1.06 to 1.03	-0.07 -0.81 to 0.70	-0.13 -1.30 to 1.05	-0.27 -1.27 to 0.81	-0.30 -0.81 to 0.21	-0.43 -1.51 to 0.70	-0.43 -1.34 to 0.49	-0.47 -1.47 to 0.59	-0.57 -1.68 to 0.61	-0.65 -1.66 to 0.44
LIRA_SC	-0.94 -1.26 to -0.62	0.67 0.19 to 1.16	0.35 -0.59 to 1.26	0.31 -0.12 to 0.75	0.21 -0.33 to 0.75	0.13 -0.25 to 0.51	0.10 -0.25 to 0.45	0.06 -1.03 to 1.06	LIRA_SC	-0.01 -0.76 to 0.74	-0.07 -0.76 to 0.62	-0.21 -0.68 to 0.27	-0.24 -1.17 to 0.65	-0.36 -0.95 to 0.21	-0.37 -0.91 to 0.16	-0.41 -0.76 to -0.06	-0.50 -1.11 to 0.08	-0.59 -1.03 to -0.14
EXENER_SC	-0.93 -1.61 to -0.23	0.68 -0.07 to 1.48	0.36 -0.19 to 0.90	0.32 -0.41 to 1.12	0.21 -0.58 to 1.05	0.13 -0.55 to 0.84	0.11 -0.63 to 0.86	0.07 -0.70 to 0.81	0.01 -0.74 to 0.76	EXENER_SC	-0.06 -0.99 to 0.88	-0.21 -0.93 to 0.58	-0.23 -0.77 to 0.29	-0.36 -1.20 to 0.49	-0.36 -0.90 to 0.20	-0.40 -1.14 to 0.35	-0.49 -1.38 to 0.41	-0.59 -1.33 to 0.20
INS_DEGLUDEC	-0.87 -1.49 to -0.20	0.74 0.25 to 1.26	0.42 -0.67 to 1.50	0.39 -0.24 to 1.03	0.28 -0.49 to 1.05	0.20 -0.45 to 0.87	0.17 -0.50 to 0.86	0.13 -1.05 to 1.30	0.07 -0.62 to 0.76	0.06 -0.88 to 0.99	INS_DEGLUDEC	-0.14 -0.87 to 0.60	-0.17 -1.26 to 0.89	-0.30 -1.09 to 0.50	-0.30 -1.08 to 0.47	-0.34 -1.01 to 0.32	-0.44 -1.26 to 0.41	-0.53 -1.24 to 0.21
INS_GLARGINE	-0.72 -1.12 to -0.34	0.89 0.37 to 1.39	0.57 -0.39 to 1.44	0.53 0.02 to 1.02	0.42 -0.01 to 0.85	0.34 0.01 to 0.67	0.31 -0.15 to 0.76	0.27 -0.81 to 1.27	0.21 -0.27 to 0.68	0.21 -0.58 to 0.93	0.14 -0.60 to 0.87	INS_GLARGINE	-0.02 -0.98 to 0.84	-0.15 -0.81 to 0.45	-0.16 -0.72 to 0.38	-0.20 -0.66 to 0.24	-0.29 -0.97 to 0.38	-0.38 -0.85 to 0.09
DAPAGLIFLOZIN	-0.69 -1.54 to 0.19	0.91 -0.01 to 1.89	0.59 0.05 to 1.14	0.56 -0.36 to 1.53	0.45 -0.50 to 1.44	0.37 -0.47 to 1.27	0.34 -0.53 to 1.26	0.30 -0.21 to 0.81	0.24 -0.65 to 1.17	0.23 -0.29 to 0.77	0.17 -0.89 to 1.26	0.02 -0.84 to 0.98	DAPAGLIFLOZIN	-0.13 -1.12 to 0.88	-0.13 -0.89 to 0.65	-0.17 -1.07 to 0.75	-0.27 -1.27 to 0.76	-0.36 -1.24 to 0.60
VISEPE_SC	-0.57 -1.06 to -0.07	1.04 0.43 to 1.67	0.72 -0.31 to 1.72	0.68 0.10 to 1.28	0.57 -0.08 to 1.26	0.49 -0.05 to 1.06	0.47 -0.12 to 1.05	0.43 -0.70 to 1.51	0.36 -0.21 to 0.95	0.36 -0.49 to 1.20	0.30 -0.50 to 1.09	0.15 -0.45 to 0.81	0.13 -0.88 to 1.12	VISEPE_SC	-0.01 -0.70 to 0.66	-0.04 -0.63 to 0.54	-0.13 -0.92 to 0.63	-0.22 -0.84 to 0.40
EXEN_SC	-0.56 -1.00 to -0.12	1.05 0.47 to 1.63	0.72 -0.07 to 1.49	0.69 0.14 to 1.25	0.58 -0.05 to 1.23	0.50 0.06 to 0.95	0.47 -0.04 to 0.99	0.43 -0.49 to 1.34	0.37 -0.16 to 0.91	0.36 -0.20 to 0.90	0.30 -0.47 to 1.08	0.16 -0.38 to 0.72	0.13 -0.65 to 0.89	0.01 -0.66 to 0.70	EXEN_SC	-0.04 -0.57 to 0.49	-0.13 -0.82 to 0.59	-0.22 -0.78 to 0.36
SITAGLIPTIN	-0.52 -0.82 to -0.20	1.09 0.65 to 1.54	0.76 -0.16 to 1.66	0.73 0.37 to 1.09	0.62 0.11 to 1.14	0.54 0.19 to 0.91	0.51 0.23 to 0.80	0.47 -0.59 to 1.47	0.41 0.06 to 0.76	0.40 -0.35 to 1.14	0.34 -0.32 to 1.01	0.20 -0.24 to 0.66	0.17 -0.75 to 1.07	0.04 -0.54 to 0.63	0.04 -0.49 to 0.57	SITAGLIPTIN	-0.10 -0.65 to 0.49	-0.18 -0.56 to 0.22
EMPAGLIFLOZIN	-0.43 -1.01 to 0.15	1.18 0.49 to 1.87	0.86 -0.20 to 1.89	0.82 0.18 to 1.47	0.71 0.00 to 1.43	0.63 0.02 to 1.23	0.60 0.10 to 1.11	0.57 -0.61 to 1.68	0.50 -0.08 to 1.11	0.49 -0.41 to 1.38	0.44 -0.41 to 1.26	0.29 -0.38 to 0.97	0.27 -0.76 to 1.27	0.13 -0.63 to 0.92	0.13 -0.59 to 0.82	0.10 -0.49 to 0.65	EMPAGLIFLOZIN	-0.09 -0.72 to 0.57
LIXI_SC	-0.34 -0.72 to 0.03	1.27 0.74 to 1.79	0.94 -0.00 to 1.87	0.91 0.42 to 1.38	0.81 0.36 to 1.24	0.72 0.31 to 1.13	0.70 0.25 to 1.11	0.65 -0.44 to 1.66	0.59 0.14 to 1.03	0.59 -0.20 to 1.33	0.53 -0.21 to 1.24	0.38 -0.09 to 0.85	0.36 -0.60 to 1.24	0.22 -0.40 to 0.84	0.22 -0.36 to 0.78	0.18 -0.22 to 0.56	0.09 -0.57 to 0.72	LIXI_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.228 (95% CrI 0.144 to 0.380)
Residual deviance: 51.7 for 52 data points
DIC: 101.8 (pD 50.1)
Largest R-hat: 1.002
Smallest ESS: bulk 2,114, tail 2,764
Divergent transitions: 0
Convergence: All criteria met
Priors: PR01 N(0, 5^2); PR03 N(0, 2.5^2); PR07 half normal(0, 0.5^2) on tau

Frequentist check (netmeta)

Method: inverse variance, REML, MD
Tau: 0.217
I squared: 86%
Q (total): 86.42 on 12 df, P = 0.000
Q (between designs): 64.16, P = 0.000

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
Dulaglutide injection versus Exenatide injection DULA_SC:EXEN_SC	1	-0.42 -0.86 to 0.03	-0.76 -1.75 to 0.23	-0.47 -0.88 to -0.07	0.532
Dulaglutide injection versus Insulin glargine DULA_SC:INS_GLARGINE	2	-0.46 -0.77 to -0.14	0.37 -0.41 to 1.15	-0.34 -0.63 to -0.05	0.053
Dulaglutide injection versus Placebo DULA_SC:PLACEBO	4	-1.00 -1.24 to -0.75	-1.36 -1.84 to -0.89	-1.07 -1.30 to -0.85	0.183
Dulaglutide injection versus Semaglutide tablet DULA_SC:SEMA_PO	1	-0.01 -0.49 to 0.48	-0.04 -0.43 to 0.35	-0.03 -0.33 to 0.28	0.917
Dulaglutide injection versus Tirzepatide injection DULA_SC:TIRZ_SC	1	0.45 -0.07 to 0.97	0.66 0.13 to 1.18	0.55 0.18 to 0.92	0.578
Exenatide injection versus Placebo EXEN_SC:PLACEBO	1	-0.53 -1.00 to -0.06	-0.85 -1.73 to 0.04	-0.60 -1.01 to -0.19	0.532
Insulin glargine with lixisenatide injection versus Insulin glargine IGLARLIXI_SC:INS_GLARGINE	1	-0.18 -0.63 to 0.27	-1.01 -1.71 to -0.30	-0.42 -0.81 to -0.04	0.053
Insulin glargine with lixisenatide injection versus Lixisenatide injection IGLARLIXI_SC:LIXI_SC	1	-1.07 -1.54 to -0.60	-0.24 -0.94 to 0.45	-0.81 -1.20 to -0.42	0.053
Liraglutide injection versus Placebo LIRA_SC:PLACEBO	2	-0.91 -1.23 to -0.58	-1.05 -1.63 to -0.47	-0.94 -1.22 to -0.66	0.673
Liraglutide injection versus Semaglutide tablet LIRA_SC:SEMA_PO	1	0.20 -0.25 to 0.65	0.02 -0.42 to 0.46	0.11 -0.21 to 0.42	0.571
Liraglutide injection versus Sitagliptin LIRA_SC:SITAGLIPTIN	1	-0.61 -1.08 to -0.14	-0.26 -0.67 to 0.15	-0.41 -0.72 to -0.10	0.274
Lixisenatide injection versus Placebo LIXI_SC:PLACEBO	1	-0.45 -0.91 to 0.01	-0.24 -0.72 to 0.24	-0.35 -0.68 to -0.02	0.540
Lixisenatide injection versus Sitagliptin LIXI_SC:SITAGLIPTIN	1	0.00 -0.51 to 0.51	0.36 -0.14 to 0.86	0.18 -0.17 to 0.54	0.323
Semaglutide tablet versus Placebo SEMA_PO:PLACEBO	1	-1.30 -1.75 to -0.85	-0.89 -1.25 to -0.53	-1.05 -1.33 to -0.77	0.163
Semaglutide injection versus Placebo SEMA_SC:PLACEBO	1	-1.42 -1.88 to -0.96	-1.13 -1.55 to -0.71	-1.26 -1.57 to -0.95	0.363
Tirzepatide injection versus Placebo TIRZ_SC:PLACEBO	1	-1.60 -2.12 to -1.08	-1.65 -2.13 to -1.17	-1.63 -1.98 to -1.28	0.889
Semaglutide tablet versus Sitagliptin SEMA_PO:SITAGLIPTIN	2	-0.40 -0.71 to -0.09	-0.76 -1.20 to -0.31	-0.52 -0.77 to -0.26	0.197
Semaglutide injection versus Sitagliptin SEMA_SC:SITAGLIPTIN	1	-0.65 -1.10 to -0.20	-0.82 -1.31 to -0.33	-0.73 -1.06 to -0.40	0.613
Semaglutide injection versus Tirzepatide injection SEMA_SC:TIRZ_SC	1	0.43 -0.00 to 0.87	0.25 -0.31 to 0.82	0.37 0.02 to 0.71	0.622

Heterogeneity within designs (decomp.design)
Design	Q	df	P
DULA_SC:INS_GLARGINE	2.71	1	0.100
PLACEBO:DULA_SC	8.40	1	0.004
SEMA_PO:SITAGLIPTIN	11.15	1	0.001

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 DAPAEXEN_SC, DAPAGLIFLOZIN, DULA_SC, EMPAGLIFLOZIN, EXEN_SC, EXENER_SC, IGLARLIXI_SC, INS_DEGLUDEC, INS_GLARGINE, LIRA_SC, LIXI_SC, SAFIGL_PO, SEMA_PO, SEMA_SC, SITAGLIPTIN, TIRZ_SC, VISEPE_SC, PLACEBO; the shaded triangle is where 95% of points would fall without small study effects. Egger type test P = 0.095.

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	DAPAEXEN_SC:DAPAGLIFLOZIN:EXENER_SC	DAPAGLIFLOZIN:SAFIGL_PO	DULA_SC:EXEN_SC:PLACEBO	DULA_SC:INS_GLARGINE	DULA_SC:PLACEBO	DULA_SC:PLACEBO:TIRZ_SC	DULA_SC:SEMA_PO	EMPAGLIFLOZIN:SEMA_PO	EXEN_SC:EXENER_SC	IGLARLIXI_SC:INS_GLARGINE	IGLARLIXI_SC:LIXI_SC	INS_DEGLUDEC:TIRZ_SC	LIRA_SC:PLACEBO	LIRA_SC:PLACEBO:SEMA_PO	LIRA_SC:SITAGLIPTIN	LIXI_SC:PLACEBO	LIXI_SC:SITAGLIPTIN	PLACEBO:SEMA_SC	PLACEBO:VISEPE_SC	SEMA_PO:SITAGLIPTIN	SEMA_SC:SITAGLIPTIN	SEMA_SC:TIRZ_SC
DAPAEXEN_SC:PLACEBO	33		29		5	2	1		27					1
DAPAGLIFLOZIN:PLACEBO	33		29		5	2	1		27					1
DULA_SC:PLACEBO			28	2	39	11	5			2	2		1	5	1	2		2		1		1
EMPAGLIFLOZIN:PLACEBO			4		5	2	9	35					4	22	2	3	3	3		8	3	1
EXEN_SC:PLACEBO			77	1	11	4	2			1	1			2		1		1				1
EXENER_SC:PLACEBO			43	1	7	3	2		40	1	1			1		1		1
IGLARLIXI_SC:PLACEBO			6	16	8	3	1			16	21		1	3	2	16	4	2		1	2
INS_DEGLUDEC:PLACEBO			4		5	26						36	1	2	1	1	1	8		1	3	11
INS_GLARGINE:PLACEBO			13	35	17	6	3			6	6		1	4	1	5	1	1			1	1
LIRA_SC:PLACEBO			1		2	1	3						31	44	6	2	2	2		1	3	1
LIXI_SC:PLACEBO			2	5	3	1	1			5	5		2	5	3	52	9	2		4	3	1
PLACEBO:SAFIGL_PO	26	21	23		4	2	1		21					1
PLACEBO:SEMA_PO			6		7	2	13						5	39	3	3	3	3		10	4	1
PLACEBO:SEMA_SC			2		3	11	1						2	5	3	2	2	45		4	10	10
PLACEBO:SITAGLIPTIN			3	1	3	3	5			1	1		6	16	11	8	8	8		14	11	2
PLACEBO:TIRZ_SC			6		7	48							1	3	1	1	1	12		1	4	15
PLACEBO:VISEPE_SC																			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 HbA1c (percent) effect modifier, prognostic factor; 25 of 25	Background glucose lowering therapy (stratum S0 to S4) effect modifier, prognostic factor; 25 of 25	Diabetes duration (years) effect modifier, prognostic factor; 24 of 25	Asian ancestry or region (percent Asian) effect modifier, prognostic factor; 24 of 25	Age (years) prognostic factor; 25 of 25	Treatment duration (weeks) effect modifier; 25 of 25
NCT03131687 S000010	8.13	S1	8.51	1.66	57.2	26
NCT02964247 S000022	8	S1	9.93	17.48	55.13	26
SURPASS-2 S000095	8.28	S1	8.63	1.32	56.57	40
PIONEER 4 S000133	7.98	S1	7.6	13.4	56.2	52
NCT01476475 S000191	8.05	S1	6.7	0.62	56.75	24
PIONEER 10 S000234	8.31	S1	9.36	100	58.43	52
NCT01584232 S000246	8.05	S1	8.85	100	56.8	26
PIONEER 2 S000251	8.1	S1	7.45	5.96	57.5	52
AWARD-10 S000305	8.04	S1	9.38	0.24	57.27	24
NCT00976937 S000415	8.13	S1	4.4	0.6	43.05	24
SUSTAIN 9 S000483	8.05	S1	9.7	23.51	57.05	30
PIONEER 12 S000522	8.12	S1	5.63	75.22	53.25	26
NCT06589765 S000558	8.6	S1	4.8 median	100 region: all sites in Asia	52.22	52
NCT02229396 S000791	9.3	S1	7.37	0.72	54.17	104
AWARD-8 S001068	8.4	S1	7.6	1.7	57.8	24
LIRA-SWITCH™ S001119	8.25	S1	7.75	not reported	56.4	26
AWARD-2 S001130	8.14	S1	9.1	16.91	56.66	78
NCT04504396 S001230	8.47	S1	5.14	100 region: all sites in Asia	53.2	24
SUSTAIN S001311	8.1	S1	6.37	85.03	53.03	30
SURPASS-3 S001591	8.17	S1	8.4	5.4	57.4	52
DURATION-NEO-1 S001982	8.5	S1	8.61	6.61	56.39	28
LIXILAN JP-O1 S002018	8.39	S1	8.67	100 region: all sites in Asia	58	52
AWARD-1 S002153	8.07	S1	8.77	2.45	55.65	52
GETGOAL-M S002188	8.06	S1	6.12	7.78	54.74	24
PIONEER 3 S002267	8.33	S1	not reported	13.14	57.75	78

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 HbA1c: design means range from 8.0 (LIRA_SC vs PLACEBO vs SEMA_PO) to 9.3 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) percent; threshold 0.5
FlagBaseline, Diabetes duration: design means range from 4.4 (LIXI_SC vs SITAGLIPTIN) to 9.9 (LIRA_SC vs PLACEBO) years; threshold 3
FlagBaseline, Asian ancestry or region: design means range from 0.6 (LIXI_SC vs SITAGLIPTIN) to 100.0 (DAPAGLIFLOZIN vs SAFIGL_PO) percent Asian; threshold 30
FlagBaseline, Age: design means range from 43.1 (LIXI_SC vs SITAGLIPTIN) to 58.4 (DULA_SC vs SEMA_PO) years; threshold 10
FlagBaseline, Treatment duration: design means range from 24.0 (DULA_SC vs PLACEBO) to 104.0 (DAPAEXEN_SC vs DAPAGLIFLOZIN vs EXENER_SC) weeks; threshold 26
NoteOutcome assessment, time point: selected time points span 24 to 32 weeks
NoteOutcome assessment, analysis set: mixed: full_analysis 11, modified_itt 13, randomized 1
NoteOutcome assessment, definition: mixed: change in HbA1c from baseline to week 26, LOCF 1, not stated 24
NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 16, not stated 8, treatment_policy 1
NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 23, not stated 2
NoteRisk of bias, blinding: mixed: double_blind 16, open_label 6, single_blind 3
NoteData handling, input conversions: arms_combined 12, n_randomized 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
NCT03131687	26	modified_itt	not stated	not stated	not stated	not stated	treatment_policy	hypothetical	double_blind	industry	2017	age 18 to 75; T2D at least 6 months; HbA1c 7.0 to 10.5%; BMI 23 to 50; diet and exercise or metformin
NCT02964247	26	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	age 18 or more; HbA1c 7.0 to 9.5%; BMI 20 or more; stable SGLT2i at least 90 days with or without metformin; eGFR 60 or more
SURPASS-2	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2019	age 18 or older, HbA1c 7.0 to 10.5 percent, BMI 25 or more, metformin 1500 mg/day or more, eGFR 45 or more
PIONEER 4	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2016	Age 18 or older; T2D on metformin with or without SGLT2i; HbA1c 7.0 to 9.5 percent; eGFR 60 or more
NCT01476475	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2011	Adults with T2D; HbA1c 7 to 10 percent on metformin at least 1.5 g/day; insulin naive
PIONEER 10	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2017	Japanese adults 20 or older; T2D; HbA1c 7.0 to 10.5 percent on one oral glucose lowering drug
NCT01584232	26	full_analysis	not stated	not stated	not stated	not stated	not stated	hypothetical	open_label	industry	2012	Japanese adults 20 years or older; BMI 18.5 to less than 35 kg/m2; HbA1c 7.0 to 10.0 percent; on sulfonylurea and/or biguanide
PIONEER 2	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	single_blind	industry	2016	type 2 diabetes on metformin; HbA1c 7.0 to 10.5 percent; eGFR 60 or more
AWARD-10	24	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	double_blind	industry	2015	T2D; HbA1c 7.0 to 9.5 percent; BMI 45 or lower; SGLT2i with or without metformin
NCT00976937	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2009	age 18 to under 50; BMI 30 or more; HbA1c 7.0 to 10 percent; metformin at least 1.5 g/day
SUSTAIN 9	30	full_analysis	not stated	not stated	not stated	not stated	not stated	not stated	double_blind	industry	2017	adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU
PIONEER 12	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2019	adults with type 2 diabetes on metformin, HbA1c 7.0 to 10.5 percent
NCT06589765	32	randomized	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2024	age 18 to 75; HbA1c 7.5 to 11.0 percent; BMI 19 to 40; metformin monotherapy; eGFR 45 or more
NCT02229396	28	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2014	age 18 or older; HbA1c 8.0 to 12.0 percent on metformin 1500 mg/d or more
AWARD-8	24	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	double_blind	industry	2013	age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose
LIRA-SWITCH™	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2013	age 18 or more; HbA1c 7.5 to 9.5 percent; BMI 20 or more; on sitagliptin 100 mg and metformin for 90 days or more
AWARD-2	26	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	open_label	industry	2010	type 2 diabetes on metformin and glimepiride
NCT04504396	24	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2020	age 18 to 75; HbA1c 7.0 to 10.5 percent; BMI 40 or lower; eGFR 60 or higher; metformin monotherapy at least 1000 mg
SUSTAIN	30	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2017	Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more
SURPASS-3	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2019	insulin naive; HbA1c 7.0 to 10.5 percent; BMI at least 25; metformin with or without SGLT2i; eGFR above 45
DURATION-NEO-1	28	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	open_label	industry	2013	Adults 18 or older; HbA1c 7.1 to 11.0 percent; diet and exercise or stable metformin, sulfonylurea, pioglitazone
LIXILAN JP-O1	26	modified_itt	change in HbA1c from baseline to week 26, LOCF	not stated	not stated	not stated	hypothetical	hypothetical	open_label	industry	2016	insulin naive Japanese adults; HbA1c 7.5 to 10%; FPG 13.8 mmol/L or less; one or two OADs
AWARD-1	26	modified_itt	not stated	not stated	not stated	not stated	not stated	hypothetical	double_blind	industry	2010	adults with type 2 diabetes on metformin and pioglitazone
GETGOAL-M	24	modified_itt	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2008	type 2 diabetes on metformin 1.5 g/day or more for 3 months; HbA1c 7 to 10 percent; FPG 13.9 mmol/L or less
PIONEER 3	26	full_analysis	not stated	not stated	not stated	not stated	hypothetical	hypothetical	double_blind	industry	2016	adults with T2D; HbA1c 7.0 to 10.5 percent; metformin with or without sulfonylurea

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
NCT03131687	A1	PLACEBO	26	arm, change	-0.060	0.140	44		R0016215:Supplement Table 1
NCT03131687	A2+A3+A4+A5	TIRZ_SC	26	arm, change	-1.659	0.051	188	arms_combined	R0016215:Supplement Table 1
NCT03131687	A6	DULA_SC	26	arm, change	-1.210	0.140	49		R0016215:Supplement Table 1
NCT02964247	A1	LIRA_SC	26	arm, change	-1.050	0.060	203		registry:outcomes
NCT02964247	A2	PLACEBO	26	arm, change	-0.350	0.080	100		registry:outcomes
SURPASS-2	A1+A2+A3	TIRZ_SC	24	arm, change	-2.313	0.025	1,410	n_randomized;arms_combined	R0007660:Table 1
SURPASS-2	A4	SEMA_SC	24	arm, change	-1.880	0.043	469	n_randomized	R0007660:Table 1
PIONEER 4	A1	SEMA_PO	26	arm, change	-1.400	0.053	285		registry:outcomes
PIONEER 4	A2	LIRA_SC	26	arm, change	-1.200	0.053	284		registry:outcomes
PIONEER 4	A3	PLACEBO	26	arm, change	-0.100	0.059	142		registry:outcomes
NCT01476475	A1	IGLARLIXI_SC	24	arm, change	-1.820	0.058	160		registry:outcomes
NCT01476475	A2	INS_GLARGINE	24	arm, change	-1.640	0.057	161		registry:outcomes
PIONEER 10	A1+A2+A3	SEMA_PO	26	arm, change	-1.593	0.061	370	arms_combined	R0018421:Figure 2D
PIONEER 10	A4	DULA_SC	26	arm, change	-1.600	0.100	62		R0018421:Figure 2D
NCT01584232	A1	DULA_SC	26	arm, change	-1.440	0.050	178		R0016159:Table 2
NCT01584232	A2	INS_GLARGINE	26	arm, change	-0.900	0.050	179		R0016159:Table 2
PIONEER 2	A1	SEMA_PO	26	arm, change	-1.500	0.054	411		registry:outcomes
PIONEER 2	A2	EMPAGLIFLOZIN	26	arm, change	-0.900	0.044	410		registry:outcomes
AWARD-10	A1+A2	DULA_SC	24	arm, change	-1.260	0.045	261	arms_combined	registry:outcomes
AWARD-10	A3	PLACEBO	24	arm, change	-0.510	0.065	123		registry:outcomes
NCT00976937	A1	LIXI_SC	24	arm, change	-0.700	0.100	150		R0012687:Results
NCT00976937	A2	SITAGLIPTIN	24	arm, change	-0.700	0.100	160		R0012687:Results
SUSTAIN 9	A1	SEMA_SC	30	contrast, md	-1.420	0.094			R0021710:Figure 1
SUSTAIN 9	A2	PLACEBO	30	contrast, md					R0021710:Figure 1
PIONEER 12	A1+A2+A3	SEMA_PO	26	arm, change	-1.233	0.032	1,082	n_randomized;arms_combined	registry:outcomes
PIONEER 12	A4	SITAGLIPTIN	26	arm, change	-0.700	0.053	359	n_randomized	registry:outcomes
NCT06589765	A1+A2+A3	SAFIGL_PO	32	arm, change	-1.586	0.045	518	arms_combined	R0029347:Table 2
NCT06589765	A4	DAPAGLIFLOZIN	32	arm, change	-1.280	0.077	190		R0029347:Table 2
NCT02229396	A1	DAPAEXEN_SC	28	arm, change	-1.980	0.094	228		R0026313:Table 3
NCT02229396	A2	EXENER_SC	28	arm, change	-1.600	0.097	227		R0026313:Table 3
NCT02229396	A3	DAPAGLIFLOZIN	28	arm, change	-1.390	0.092	230		R0026313:Table 3
AWARD-8	A1	DULA_SC	24	arm, change	-1.380	0.080	215		registry:outcomes
AWARD-8	A2	PLACEBO	24	arm, change	-0.110	0.140	53		registry:outcomes
LIRA-SWITCH™	A1	LIRA_SC	26	contrast, md	-0.610	0.107			R0025720:Results
LIRA-SWITCH™	A2	SITAGLIPTIN	26	contrast, md					R0025720:Results
AWARD-2	A1+A2	DULA_SC	26	arm, change	-1.024	0.039	529	arms_combined	registry:outcomes
AWARD-2	A3	INS_GLARGINE	26	arm, change	-0.650	0.060	258		registry:outcomes
NCT04504396	A1	VISEPE_SC	24	arm, change	-1.270	0.054	310		R0009432:Table 2
NCT04504396	A2	PLACEBO	24	arm, change	-0.700	0.051	310		R0009432:Table 2
SUSTAIN	A1+A2	SEMA_SC	30	arm, change	-1.651	0.042	578	arms_combined	registry:outcomes
SUSTAIN	A3	SITAGLIPTIN	30	arm, change	-1.000	0.053	290		registry:outcomes
SURPASS-3	A1+A2+A3	TIRZ_SC	24	arm, change	-2.097	0.026	1,079	n_randomized;arms_combined	R0007660:Table 1
SURPASS-3	A4	INS_DEGLUDEC	24	arm, change	-1.360	0.045	365	n_randomized	R0007660:Table 1
DURATION-NEO-1	A1	EXENER_SC	28	arm, change	-1.450	0.102	229	n_randomized	R0022632:Results
DURATION-NEO-1	A2	EXEN_SC	28	arm, change	-1.040	0.122	148	n_randomized	R0022632:Results
LIXILAN JP-O1	A1	IGLARLIXI_SC	26	arm, change	-1.580	0.072	161		R0015751:Table 2
LIXILAN JP-O1	A2	LIXI_SC	26	arm, change	-0.510	0.073	160		R0015751:Table 2
AWARD-1	A1+A2	DULA_SC	26	arm, change	-1.405	0.043	540	arms_combined	registry:outcomes
AWARD-1	A3	EXEN_SC	26	arm, change	-0.990	0.060	266		registry:outcomes
AWARD-1	A4	PLACEBO	26	arm, change	-0.460	0.080	119		registry:outcomes
GETGOAL-M	A1+A2	LIXI_SC	24	arm, change	-0.851	0.050	483	arms_combined	R0025872:Results
GETGOAL-M	A3	PLACEBO	24	arm, change	-0.400	0.080	164		R0025872:Results
PIONEER 3	A1+A2+A3	SEMA_PO	26	arm, change	-1.066	0.029	1,396	arms_combined	registry:outcomes
PIONEER 3	A4	SITAGLIPTIN	26	arm, change	-0.800	0.042	467		registry:outcomes

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