LivingGLP1
Network meta-analysis

HbA1c change

Type 2 diabetes (adults); background therapy: no glucose lowering drug (lifestyle only)

weeks 36 to 64 (target week 52)Hypothetical (as if everyone stayed on treatment)Each dose separatelyMean difference
5
Randomized trials
12
Treatments
2,665
Participants
18
Trial arms

In plain language

Across 5 trials with 2,665 participants, 8 of 11 treatments had a clearly better result than placebo on HbA1c change, and for 3 the evidence could not tell them apart from placebo. The most favorable estimate was for tirzepatide 15 mg subcutaneous once weekly: mean difference -2.11 percentage points (95% credible interval -2.53 to -1.54).

  • Tirzepatide 15 mg subcutaneous once weekly: among the most effective (certainty pending).
  • Tirzepatide 10 mg subcutaneous once weekly: among the most effective (certainty pending).
  • Tirzepatide 5 mg subcutaneous once weekly: among the most effective (certainty pending).
  • Orforglipron 12 mg oral once daily: better than placebo but not among the most effective (certainty pending).
  • Orforglipron 36 mg oral once daily: better than placebo but not among the most effective (certainty pending).
  • Orforglipron 3 mg oral once daily: better than placebo but not among the most effective (certainty pending).
  • Albiglutide 50 mg subcutaneous once weekly: better than placebo but not among the most effective (certainty pending).
  • Albiglutide 30 mg subcutaneous once weekly: better than placebo but not among the most effective (certainty pending).
  • Dulaglutide 1.5 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
  • Dulaglutide 0.75 mg subcutaneous once weekly: not convincingly different from placebo (certainty pending).
  • Metformin: 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.
ALBI_SC_30MG_QWALBI_SC_50MG_QWDULA_SC_0p75MG_QWDULA_SC_1p5MG_QWMETFORMINORFO_PO_12MG_QDORFO_PO_36MG_QDORFO_PO_3MG_QDPLACEBOTIRZ_SC_10MG_QWTIRZ_SC_15MG_QWTIRZ_SC_5MG_QW
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.
-2.5-2-1.5-1-0.500.5← favors treatmentfavors reference →Tirzepatide 15 mg subcutaneous o…Tirzepatide 10 mg subcutaneous o…Tirzepatide 5 mg subcutaneous on…Orforglipron 12 mg oral once dailyOrforglipron 36 mg oral once dailyOrforglipron 3 mg oral once dailyAlbiglutide 50 mg subcutaneous o…Albiglutide 30 mg subcutaneous o…Dulaglutide 1.5 mg subcutaneous …Dulaglutide 0.75 mg subcutaneous…Metformin
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
TreatmentBayesian MD (95% CrI)95% prediction intervalFrequentist MD (95% CI)VerdictConfidence
Tirzepatide 15 mg subcutaneous once weekly
TIRZ_SC_15MG_QW
-2.11 (-2.53 to -1.54)-2.71 to -1.33-2.15 (-2.41 to -1.89)Betterpending
Tirzepatide 10 mg subcutaneous once weekly
TIRZ_SC_10MG_QW
-1.92 (-2.34 to -1.34)-2.51 to -1.14-1.96 (-2.21 to -1.70)Betterpending
Tirzepatide 5 mg subcutaneous once weekly
TIRZ_SC_5MG_QW
-1.81 (-2.22 to -1.24)-2.40 to -1.05-1.85 (-2.11 to -1.59)Betterpending
Orforglipron 12 mg oral once daily
ORFO_PO_12MG_QD
-1.42 (-1.89 to -0.87)-2.09 to -0.65-1.44 (-1.72 to -1.16)Betterpending
Orforglipron 36 mg oral once daily
ORFO_PO_36MG_QD
-1.28 (-1.77 to -0.69)-1.93 to -0.52-1.30 (-1.60 to -1.00)Betterpending
Orforglipron 3 mg oral once daily
ORFO_PO_3MG_QD
-1.09 (-1.61 to -0.49)-1.78 to -0.31-1.11 (-1.42 to -0.80)Betterpending
Albiglutide 50 mg subcutaneous once weekly
ALBI_SC_50MG_QW
-1.03 (-1.52 to -0.48)-1.68 to -0.30-1.04 (-1.31 to -0.77)Betterpending
Albiglutide 30 mg subcutaneous once weekly
ALBI_SC_30MG_QW
-0.84 (-1.32 to -0.31)-1.53 to -0.12-0.85 (-1.12 to -0.58)Betterpending
Dulaglutide 1.5 mg subcutaneous once weekly
DULA_SC_1p5MG_QW
-0.78 (-1.42 to 0.09)-1.56 to 0.29-0.83 (-1.21 to -0.46)Unclearpending
Dulaglutide 0.75 mg subcutaneous once weekly
DULA_SC_0p75MG_QW
-0.64 (-1.15 to 0.06)-1.30 to 0.24-0.68 (-1.01 to -0.36)Unclearpending
Metformin
METFORMIN
-0.59 (-1.28 to 0.28)-1.40 to 0.45-0.64 (-1.02 to -0.27)Unclearpending

Confidence in the results

How much each comparison can be trusted, rated with CINeMA in six domains and summarized with GRADE.
Confidence in each comparison with Placebo
ComparisonWithin study biasReporting biasIndirectnessImprecisionHeterogeneityIncoherenceConfidence
Albiglutide 30 mg subcutaneous once weekly versus Placebopendingsomependingnonesomesomepending
Albiglutide 50 mg subcutaneous once weekly versus Placebopendingsomependingnonenonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Placebopendingsomependingsomenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Placebopendingsomependingsomenonesomepending
Metformin versus Placebopendingsomependingsomesomesomepending
Orforglipron 3 mg oral once daily versus Placebopendingsomependingnonesomesomepending
Orforglipron 12 mg oral once daily versus Placebopendingsomependingnonenonesomepending
Orforglipron 36 mg oral once daily versus Placebopendingsomependingnonenonesomepending
Tirzepatide 5 mg subcutaneous once weekly versus Placebopendingsomependingnonenonesomepending
Tirzepatide 10 mg subcutaneous once weekly versus Placebopendingsomependingnonenonesomepending
Tirzepatide 15 mg subcutaneous once weekly versus Placebopendingsomependingnonenonesomepending
Every other comparison (55)
Confidence in the other comparisons
ComparisonWithin study biasReporting biasIndirectnessImprecisionHeterogeneityIncoherenceConfidence
Albiglutide 30 mg subcutaneous once weekly versus Albiglutide 50 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Dulaglutide 0.75 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Dulaglutide 0.75 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Dulaglutide 1.5 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Metforminpendingsomependingmajornonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Metforminpendingsomependingmajornonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Metforminpendingsomependingmajornonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Metforminpendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Metformin versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Orforglipron 12 mg oral once daily versus Orforglipron 3 mg oral once dailypendingsomependingsomesomesomepending
Orforglipron 36 mg oral once daily versus Orforglipron 3 mg oral once dailypendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 12 mg oral once dailypendingsomependingsomesomesomepending
Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 12 mg oral once dailypendingsomependingmajornonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 12 mg oral once dailypendingsomependingsomenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 12 mg oral once dailypendingsomependingsomesomesomepending
Metformin versus Orforglipron 12 mg oral once dailypendingsomependingsomenonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Orforglipron 36 mg oral once dailypendingsomependingmajornonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Orforglipron 36 mg oral once dailypendingsomependingmajornonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Orforglipron 36 mg oral once dailypendingsomependingsomenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Orforglipron 36 mg oral once dailypendingsomependingmajornonesomepending
Metformin versus Orforglipron 36 mg oral once dailypendingsomependingsomesomesomepending
Orforglipron 12 mg oral once daily versus Orforglipron 36 mg oral once dailypendingsomependingmajornonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingnonesomesomepending
Metformin versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Orforglipron 3 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Orforglipron 12 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingmajornonesomepending
Orforglipron 36 mg oral once daily versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomesomesomepending
Tirzepatide 10 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomesomesomepending
Tirzepatide 15 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weeklypendingsomependingsomesomesomepending
Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingnonesomesomepending
Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Metformin versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Orforglipron 3 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Orforglipron 12 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingsomesomesomepending
Orforglipron 36 mg oral once daily versus Tirzepatide 10 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Albiglutide 30 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Albiglutide 50 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingnonesomesomepending
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Dulaglutide 1.5 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Metformin versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingnonenonesomepending
Orforglipron 3 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Orforglipron 12 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Orforglipron 36 mg oral once daily versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingsomenonesomepending
Tirzepatide 10 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weeklypendingsomependingsomesomesomepending

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
TreatmentRank 1Rank 2Rank 3Rank 4Rank 5Rank 6Rank 7Rank 8Rank 9Rank 10Rank 11Rank 12Mean rank
TIRZ_SC_15MG_QW85%11%3%1%1%1.2
TIRZ_SC_10MG_QW9%65%20%3%2%1%2.3
TIRZ_SC_5MG_QW3%19%67%7%2%1%1%3.0
ORFO_PO_12MG_QD2%3%5%58%20%6%3%1%1%4.4
ORFO_PO_36MG_QD1%1%2%17%47%17%7%4%2%1%1%5.3
ORFO_PO_3MG_QD1%4%11%38%21%13%5%3%3%6.7
ALBI_SC_50MG_QW1%5%10%21%34%15%6%5%2%6.9
ALBI_SC_30MG_QW1%2%5%14%36%16%10%14%8.4
DULA_SC_1p5MG_QW2%3%6%13%18%35%13%7%2%8.4
DULA_SC_0p75MG_QW1%2%3%7%21%40%25%1%9.7
METFORMIN1%1%2%3%6%13%25%44%5%10.0
PLACEBO2%2%4%92%11.9

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 columnPLACEBOTIRZ_SC_15MG_QWTIRZ_SC_10MG_QWTIRZ_SC_5MG_QWORFO_PO_12MG_QDORFO_PO_36MG_QDORFO_PO_3MG_QDALBI_SC_50MG_QWALBI_SC_30MG_QWDULA_SC_1p5MG_QWDULA_SC_0p75MG_QWMETFORMIN
PLACEBOPLACEBO2.11
1.54 to 2.53		1.92
1.34 to 2.34		1.81
1.24 to 2.22		1.42
0.87 to 1.89		1.28
0.69 to 1.77		1.09
0.49 to 1.61		1.03
0.48 to 1.52		0.84
0.31 to 1.32		0.78
-0.09 to 1.42		0.64
-0.06 to 1.15		0.59
-0.28 to 1.28
TIRZ_SC_15MG_QW-2.11
-2.53 to -1.54		TIRZ_SC_15MG_QW-0.19
-0.57 to 0.19		-0.30
-0.68 to 0.08		-0.69
-1.37 to 0.02		-0.83
-1.53 to -0.08		-1.01
-1.71 to -0.24		-1.08
-1.74 to -0.31		-1.26
-1.93 to -0.51		-1.33
-2.05 to -0.70		-1.47
-1.97 to -1.01		-1.52
-2.21 to -0.83
TIRZ_SC_10MG_QW-1.92
-2.34 to -1.34		0.19
-0.19 to 0.57		TIRZ_SC_10MG_QW-0.11
-0.51 to 0.28		-0.50
-1.16 to 0.25		-0.64
-1.34 to 0.10		-0.83
-1.52 to -0.07		-0.89
-1.53 to -0.11		-1.08
-1.74 to -0.33		-1.14
-1.86 to -0.50		-1.28
-1.80 to -0.79		-1.33
-2.03 to -0.66
TIRZ_SC_5MG_QW-1.81
-2.22 to -1.24		0.30
-0.08 to 0.68		0.11
-0.28 to 0.51		TIRZ_SC_5MG_QW-0.39
-1.05 to 0.35		-0.53
-1.22 to 0.20		-0.72
-1.42 to 0.04		-0.78
-1.44 to -0.03		-0.97
-1.62 to -0.23		-1.03
-1.77 to -0.38		-1.17
-1.67 to -0.69		-1.22
-1.91 to -0.53
ORFO_PO_12MG_QD-1.42
-1.89 to -0.87		0.69
-0.02 to 1.37		0.50
-0.25 to 1.16		0.39
-0.35 to 1.05		ORFO_PO_12MG_QD-0.14
-0.66 to 0.39		-0.33
-0.85 to 0.22		-0.39
-1.10 to 0.38		-0.58
-1.28 to 0.17		-0.64
-1.61 to 0.21		-0.78
-1.62 to -0.03		-0.83
-1.80 to 0.08
ORFO_PO_36MG_QD-1.28
-1.77 to -0.69		0.83
0.08 to 1.53		0.64
-0.10 to 1.34		0.53
-0.20 to 1.22		0.14
-0.39 to 0.66		ORFO_PO_36MG_QD-0.19
-0.73 to 0.35		-0.24
-0.96 to 0.50		-0.43
-1.15 to 0.33		-0.50
-1.49 to 0.35		-0.64
-1.48 to 0.11		-0.69
-1.66 to 0.20
ORFO_PO_3MG_QD-1.09
-1.61 to -0.49		1.01
0.24 to 1.71		0.83
0.07 to 1.52		0.72
-0.04 to 1.42		0.33
-0.22 to 0.85		0.19
-0.35 to 0.73		ORFO_PO_3MG_QD-0.06
-0.81 to 0.72		-0.25
-1.01 to 0.55		-0.32
-1.34 to 0.53		-0.46
-1.33 to 0.31		-0.50
-1.50 to 0.39
ALBI_SC_50MG_QW-1.03
-1.52 to -0.48		1.08
0.31 to 1.74		0.89
0.11 to 1.53		0.78
0.03 to 1.44		0.39
-0.38 to 1.10		0.24
-0.50 to 0.96		0.06
-0.72 to 0.81		ALBI_SC_50MG_QW-0.19
-0.68 to 0.32		-0.25
-1.25 to 0.58		-0.39
-1.23 to 0.32		-0.43
-1.43 to 0.41
ALBI_SC_30MG_QW-0.84
-1.32 to -0.31		1.26
0.51 to 1.93		1.08
0.33 to 1.74		0.97
0.23 to 1.62		0.58
-0.17 to 1.28		0.43
-0.33 to 1.15		0.25
-0.55 to 1.01		0.19
-0.32 to 0.68		ALBI_SC_30MG_QW-0.06
-1.07 to 0.76		-0.20
-1.08 to 0.51		-0.25
-1.22 to 0.60
DULA_SC_1p5MG_QW-0.78
-1.42 to 0.09		1.33
0.70 to 2.05		1.14
0.50 to 1.86		1.03
0.38 to 1.77		0.64
-0.21 to 1.61		0.50
-0.35 to 1.49		0.32
-0.53 to 1.34		0.25
-0.58 to 1.25		0.06
-0.76 to 1.07		DULA_SC_1p5MG_QW-0.14
-0.62 to 0.38		-0.19
-0.66 to 0.33
DULA_SC_0p75MG_QW-0.64
-1.15 to 0.06		1.47
1.01 to 1.97		1.28
0.79 to 1.80		1.17
0.69 to 1.67		0.78
0.03 to 1.62		0.64
-0.11 to 1.48		0.46
-0.31 to 1.33		0.39
-0.32 to 1.23		0.20
-0.51 to 1.08		0.14
-0.38 to 0.62		DULA_SC_0p75MG_QW-0.05
-0.54 to 0.46
METFORMIN-0.59
-1.28 to 0.28		1.52
0.83 to 2.21		1.33
0.66 to 2.03		1.22
0.53 to 1.91		0.83
-0.08 to 1.80		0.69
-0.20 to 1.66		0.50
-0.39 to 1.50		0.43
-0.41 to 1.43		0.25
-0.60 to 1.22		0.19
-0.33 to 0.66		0.05
-0.46 to 0.54		METFORMIN

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau)
0.126 (95% CrI 0.006 to 0.565)
Residual deviance
17.4 for 18 data points
DIC
34.3 (pD 17.0)
Largest R-hat
1.002
Smallest ESS
bulk 1,114, tail 1,514
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
0.000
I squared
0%
Q (total)
1.27 on 2 df, P = 0.529
Q (between designs)
1.27, P = 0.529

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.
ComparisonTrialsDirectIndirectNetworkP
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 10 mg subcutaneous once weekly
DULA_SC_0p75MG_QW:TIRZ_SC_10MG_QW
11.30
1.02 to 1.58
1.14
0.53 to 1.74
1.27
1.02 to 1.52
0.629
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 15 mg subcutaneous once weekly
DULA_SC_0p75MG_QW:TIRZ_SC_15MG_QW
11.50
1.22 to 1.78
1.28
0.67 to 1.89
1.46
1.21 to 1.71
0.516
Dulaglutide 0.75 mg subcutaneous once weekly versus Tirzepatide 5 mg subcutaneous once weekly
DULA_SC_0p75MG_QW:TIRZ_SC_5MG_QW
11.10
0.82 to 1.38
1.48
0.88 to 2.08
1.17
0.91 to 1.42
0.261
Tirzepatide 10 mg subcutaneous once weekly versus Placebo
TIRZ_SC_10MG_QW:PLACEBO
1-1.93
-2.21 to -1.65
-2.11
-2.79 to -1.43
-1.96
-2.21 to -1.70
0.629
Tirzepatide 15 mg subcutaneous once weekly versus Placebo
TIRZ_SC_15MG_QW:PLACEBO
1-2.11
-2.39 to -1.83
-2.35
-3.01 to -1.69
-2.15
-2.41 to -1.89
0.516
Tirzepatide 5 mg subcutaneous once weekly versus Placebo
TIRZ_SC_5MG_QW:PLACEBO
1-1.91
-2.19 to -1.63
-1.48
-2.17 to -0.79
-1.85
-2.11 to -1.59
0.261

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.
0.000.090.17-0.36-0.180.000.180.36Centered effectStandard error
Comparisons ordered as ALBI_SC_30MG_QW, ALBI_SC_50MG_QW, DULA_SC_0p75MG_QW, DULA_SC_1p5MG_QW, METFORMIN, ORFO_PO_12MG_QD, ORFO_PO_36MG_QD, ORFO_PO_3MG_QD, TIRZ_SC_10MG_QW, TIRZ_SC_15MG_QW, TIRZ_SC_5MG_QW, PLACEBO; the shaded triangle is where 95% of points would fall without small study effects. Egger type test P = 0.816.

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 estimateALBI_SC_30MG_QW:ALBI_SC_50MG_QW:PLACEBODULA_SC_0p75MG_QW:DULA_SC_1p5MG_QW:METFORMINDULA_SC_0p75MG_QW:TIRZ_SC_10MG_QW:TIRZ_SC_15MG_QW:TIRZ_SC_5MG_QWORFO_PO_12MG_QD:ORFO_PO_36MG_QD:ORFO_PO_3MG_QD:PLACEBOPLACEBO:TIRZ_SC_10MG_QW:TIRZ_SC_15MG_QW:TIRZ_SC_5MG_QW
ALBI_SC_30MG_QW:PLACEBO100
ALBI_SC_50MG_QW:PLACEBO100
DULA_SC_0p75MG_QW:PLACEBO5050
DULA_SC_1p5MG_QW:PLACEBO393131
METFORMIN:PLACEBO393131
ORFO_PO_12MG_QD:PLACEBO100
ORFO_PO_36MG_QD:PLACEBO100
ORFO_PO_3MG_QD:PLACEBO100
PLACEBO:TIRZ_SC_10MG_QW1783
PLACEBO:TIRZ_SC_15MG_QW1882
PLACEBO:TIRZ_SC_5MG_QW1783

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
TrialBaseline HbA1c (percent)
effect modifier, prognostic factor; 5 of 5
Background glucose lowering therapy (stratum S0 to S4)
effect modifier, prognostic factor; 5 of 5
Diabetes duration (years)
effect modifier, prognostic factor; 5 of 5
Asian ancestry or region (percent Asian)
effect modifier, prognostic factor; 5 of 5
Age (years)
prognostic factor; 5 of 5
Treatment duration (weeks)
effect modifier; 5 of 5
SURPASS J-mono
S000239
8.2S05.9510056.6252
SURPASS-1
S000407
7.97S04.735.1554.1140
NCT00849017
S000852
8.07S03.972.3652.9156
NCT01126580
S001786
7.6S02.637.5655.5652
ACHIEVE-1
S001950
7.98S04.443.8353.3740

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 7.6 (DULA_SC_0p75MG_QW vs DULA_SC_1p5MG_QW vs METFORMIN) to 8.2 (DULA_SC_0p75MG_QW vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) percent; threshold 0.5
  • FlagBaseline, Diabetes duration: design means range from 2.6 (DULA_SC_0p75MG_QW vs DULA_SC_1p5MG_QW vs METFORMIN) to 5.9 (DULA_SC_0p75MG_QW vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) years; threshold 3
  • FlagBaseline, Asian ancestry or region: design means range from 2.4 (ALBI_SC_30MG_QW vs ALBI_SC_50MG_QW vs PLACEBO) to 100.0 (DULA_SC_0p75MG_QW vs TIRZ_SC_10MG_QW vs TIRZ_SC_15MG_QW vs TIRZ_SC_5MG_QW) percent Asian; threshold 30
  • FlagBaseline, Treatment duration: design means range from 40.0 (ORFO_PO_12MG_QD vs ORFO_PO_36MG_QD vs ORFO_PO_3MG_QD vs PLACEBO) to 156.0 (ALBI_SC_30MG_QW vs ALBI_SC_50MG_QW vs PLACEBO) weeks; threshold 26
  • NoteOutcome assessment, time point: selected time points span 40 to 52 weeks
  • NoteOutcome assessment, intercurrent events (discontinuation): mixed: hypothetical 4, not stated 1
  • NoteOutcome assessment, intercurrent events (rescue): mixed: hypothetical 4, not stated 1
Comparability items per trial
Trialtime weeksanalysis setdefinitioninstrumentadjudicatedproportion methodintercurrent events (discontinuation)intercurrent events (rescue)blindingfundingstart yearEligibility
SURPASS J-mono52modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2019Japanese adults 20 or older; BMI 23 or more; HbA1c 7.0 to 10.0 percent; drug naive or oral monotherapy washed out
SURPASS-140modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2019adults; HbA1c 7.0 to 9.5 percent; BMI 23 or higher; no glucose lowering drug in prior 90 days
NCT0084901752modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2009age 18 or older; HbA1c 7.0 to 10.0 percent; BMI 20 to 45; diet and exercise only
NCT0112658052modified_ittnot statednot statednot statednot statednot statednot stateddouble_blindindustry2010type 2 diabetes on diet and exercise or one oral drug; registry gives no ranges
ACHIEVE-140modified_ittnot statednot statednot statednot statedhypotheticalhypotheticaldouble_blindindustry2023adults 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
TrialArmTreatmentWeekDataValueSEEvents / NFlagsSource
SURPASS J-monoA1TIRZ_SC_5MG_QW52arm, change-2.4000.100142R0012580:Table 2
SURPASS J-monoA2TIRZ_SC_10MG_QW52arm, change-2.6000.100135R0012580:Table 2
SURPASS J-monoA3TIRZ_SC_15MG_QW52arm, change-2.8000.100134R0012580:Table 2
SURPASS J-monoA4DULA_SC_0p75MG_QW52arm, change-1.3000.100138R0012580:Table 2
SURPASS-1A1TIRZ_SC_5MG_QW40arm, change-1.8700.094121registry:outcomes
SURPASS-1A2TIRZ_SC_10MG_QW40arm, change-1.8900.096118registry:outcomes
SURPASS-1A3TIRZ_SC_15MG_QW40arm, change-2.0700.098116registry:outcomes
SURPASS-1A4PLACEBO40arm, change0.0400.105112registry:outcomes
NCT00849017A1PLACEBO52arm, change0.1500.09798registry:outcomes
NCT00849017A2ALBI_SC_30MG_QW52arm, change-0.7000.096100registry:outcomes
NCT00849017A3ALBI_SC_50MG_QW52arm, change-0.8900.09797registry:outcomes
NCT01126580A1DULA_SC_1p5MG_QW52arm, change-0.7000.070265registry:outcomes
NCT01126580A2DULA_SC_0p75MG_QW52arm, change-0.5500.070265registry:outcomes
NCT01126580A3METFORMIN52arm, change-0.5100.070265registry:outcomes
ACHIEVE-1A1PLACEBO40arm, change-0.1500.113138registry:outcomes
ACHIEVE-1A2ORFO_PO_3MG_QD40arm, change-1.2600.114143registry:outcomes
ACHIEVE-1A3ORFO_PO_12MG_QD40arm, change-1.5900.087137registry:outcomes
ACHIEVE-1A4ORFO_PO_36MG_QD40arm, change-1.4500.104141registry:outcomes

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