1. Summary of findings table for NMA.
| Bayesian NMA‐SoF table | ||||
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Patient or population: participants with CVD Interventions: dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide 1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors Comparator (reference): placebo Outcome: cardiovascular mortality, fatal or non‐fatal myocardial infarction,fatal or non‐fatal stroke, all‐cause mortality, hospitalisation for heart failure, development of end‐stage kidney disease, non‐cardiac safety outcomes (hypoglycaemia), non‐cardiac safety outcomes (pancreatitis), non‐cardiac safety outcomes (fractures). Setting(s): outpatient Geometry of the Network: separately attached (Figure 4) |
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| Cardiovascular mortality |
Relative effect (network estimate)* OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference comparator | Reference comparator | 1 (Worst) | |
| DPP4i (Direct evidence; 47,968 participants, 6 RCTs) |
0.99 (0.87 to 1.1) | ⊕⊕⊕⊕ HIGH |
2 | |
| GLP1‐RA (Direct evidence; 46,093 participants, 6 RCTs) |
0.87 (0.76 to 0.98) | ⊕⊕⊕⊕ HIGH |
3 | |
| SGLT2i (Direct evidence; 24,962 participants, 5 RCTs) |
0.82 (0.72 to 0.94) | ⊕⊕⊕⊝ MODERATE1 |
4 (Best) | |
| Fatal or non‐fatal myocardial infarction |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference comparator | Reference comparator | 1 (Worst) | |
| DPP4i (Direct evidence; 42,334 participants, 4 RCTs) |
0.98 (0.84 to 1.1) | ⊕⊕⊕⊕ HIGH |
2 | |
| GLP1‐RA (Direct evidence; 42,910 participants, 5 RCTs) |
0.89 (0.77 to 1.0) | ⊕⊕⊕⊝ MODERATE1 |
4 (Best) | |
| SGLT2i (Direct evidence; 15,266 participants, 2 RCTs) |
0.97 (0.77 to 1.2) | ⊕⊕⊕⊕ HIGH |
3 | |
| Fatal or non‐fatal stroke |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference comparator | Reference comparator | 2 | |
| DPP4i (Direct evidence; 42,588 participants, 5 RCTs) |
0.99 (0.84 to 1.2) | ⊕⊕⊕⊕ HIGH |
3 | |
| GLP1‐RA (Direct evidence; 42,910 participants, 5 RCTs) |
0.87 (0.75 to 1.0) | ⊕⊕⊕⊕ HIGH |
4 (Best) | |
| SGLT2i (Direct evidence; 15,266 participants, 2 RCTs) |
1.1 (0.89 to 1.4) | ⊕⊕⊕⊝ MODERATE2 |
1 (Worst) | |
| All‐cause mortality |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference Comparator | Reference Comparator | 2 | |
| DPP4i (Direct evidence; 47968 participants, 6 RCTs) |
1.0 (0.93 to 1.2) | ⊕⊕⊕⊕ HIGH |
1 (Worst) | |
| GLP1‐RA (Direct evidence; 46,393 participants, 7 RCTs) |
0.88 (0.79 to 0.98) | ⊕⊕⊕⊕ HIGH |
3 | |
| SGLT2i (Direct evidence; 24962 participants, 5 RCTs) |
0.84 (0.75 to 0.93) | ⊕⊕⊕⊝ Moderate1 |
4 (Best) | |
| Hospitalisation for heart failure |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking*** | |
| Placebo | Reference comparator | Reference comparator | 2 | |
| DPP4i (Direct evidence; 42,334 participants, 4 RCTs) |
1.0 (0.84 to 1.2) | ⊕⊕⊕◯ MODERATE1 |
1 (Worst) | |
| GLP1‐RA (Direct evidence; 36,930 participants, 6 RCTs) |
0.97 (0.83 to 1.1) | ⊕⊕⊕⊕ HIGH |
3 | |
| SGLT2i (Direct evidence; 24962 participants, 5 RCTs) |
0.64 (0.55 to 0.74) | ⊕⊕⊕⊕ High |
4 (Best) | |
| Safety outcome (worsening renal function) |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference Comparator | Reference Comparator | 2 | |
| DPP4i (Direct evidence; 16,492 participants, 1 RCT) |
1.1 (0.50 to 2.4) | ⊕⊕⊝⊝ LOW2, 3 |
1 (Worst) | |
| GLP1‐RA (Direct evidence; 3297 participants, 1 RCT) |
0.61 (0.27 to 1.4) | ⊕⊕⊝⊝ LOW5 |
3 | |
| SGLT2i (Direct evidence; 8474 participants, 2 RCTs) |
0.60 (0.32 to 1.1) | ⊕⊕⊝⊝ LOW2, 4 |
4 (Best) | |
| Safety outcome (pancreatitis) |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference comparator | Reference comparator | 2 | |
| DPP4i (Direct evidence; 47684 participants, 5 RCTs) |
1.6 (1.1 to 2.6) | ⊕⊕⊕⊝ MODERATE4 |
1 (Worst) | |
| GLP1‐RA (Direct evidence; 40,035 participants, 5 RCTs) |
0.95 (0.62 to 1.4) | ⊕⊕⊝⊝ LOW2, 3 |
3 | |
| SGLT2i (Direct evidence; 8,246 participants, 1 RCT) |
0.86 (0.35 to 2.2) | ⊕⊕⊝⊝ LOW5 |
4 (Best) | |
| Safety outcome (fracture) |
Relative effect (network estimate) OR (95% CrI) |
Certainty of the evidence | Ranking** | |
| Placebo | Reference comparator | Reference comparator | 2 | |
| DPP4i (Direct evidence; 16,492 participants, 1 RCT) |
1.0 (0.73 to 1.4) | ⊕⊕⊝⊝ LOW2,3 |
3 (Best) | |
| GLP1‐RA (No direct evidence; 0participants, 0 RCTs) |
‐ | ‐ | ‐ | |
| SGLT2i (Direct evidence; 24,962 participants, 5 RCTs) |
1.0 (0.84 to 1.2) | ⊕⊕⊕⊕ HIGH |
1 (Worst) | |
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NMA‐SoF table definitions * Network meta‐analysis estimates are reported as odds ratio. CrI: credible interval. Results are expressed in credible intervals as opposed to the confidence intervals since a Bayesian analysis has been conducted. ** Rank statistics is defined as the ranking order such that a treatment out of n treatments in a network meta‐analysis isthe worst, the second, the third and so on until thebest effective treatment. |
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GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect |
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Explanatory Footnotes 1Moderate to substantial heterogeneity in effect (‐1): Inconsistency 2The 95% CrI includes no effect and includes default values for appreciable harm (i.e. CI > 1.25), appreciable benefit (i.e. CI < 0.75), or both. (‐1): Imprecision 3Only 1 RCT was included for this outcome. (‐1): Imprecision 4The number of outcome events was small. (‐1): Imprecision 5Downgrade with 2, 3, and 4. (‐2): Imprecision |
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CI: confidence interval, Crl: credible interval, CVD: cardiovascular disease, DPP4i: dipeptidyl peptidase 4 inhibitor, GLP‐1RA: glucagon‐like peptide‐1 receptor agonist, NMA: network meta‐analysis, OR: odds ratio, RCT: randomized controlled trial, SGLT2i: sodium‐glucose co‐transporter‐2 inhibitor