Structured population data were available for 7 of 7 supporting studies. 6 studies described participants with type 2 diabetes. 7 studies described adult participants.

4 supporting studies do not have a displayable topic-matched quantitative effect.

Evidence uses heterogeneous comparison contexts: placebo, usual_care.

3 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

1 study contains conflicting p-value and significance fields; those significance claims are suppressed.

Placebo

Core clinician-reference fields are available or not applicable.

Participants receiving liraglutide in the LEADER trial.

Liraglutide

Individual-level data consisting of 9340 (liraglutide: 4668; placebo: 4672) and 3297 (semaglutide: 1648; placebo: 1649) subjects from the LEADER and SUSTAIN-6 trials, respectively, was utilized for this study.

Participants receiving semaglutide in the SUSTAIN-6 trial.

Semaglutide

Participants receiving placebo in the LEADER trial.

Participants receiving placebo in the SUSTAIN-6 trial.

HbA1c mediates cardiovascular benefits of GLP-1 receptor agonists

Available source content was suppressed because validation identified a conflict.

Standard care for diabetes management

Participants receiving oral semaglutide for primary prevention of cardiovascular events.

Oral Semaglutide Group

ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK.

Participants receiving standard care for diabetes management.

The trial includes a comparator group receiving standard care for diabetes management.

Authoritative quality diagnostic: invalid or missing timepoint.

Authoritative quality diagnostic: invalid or missing unit.

Authoritative quality diagnostic: invalid or missing value.

Oral semaglutide may improve cardiovascular event prevention in type 2 diabetes.

Participants received oral semaglutide in addition to standard of care.

Oral Semaglutide

Participants were randomized to oral semaglutide, 3 mg, or matched placebo once daily for 4 weeks, followed by 7 mg once daily for 4 weeks, then 14 mg once daily until the end of the trial.

Participants received matched placebo in addition to standard of care.

Authoritative quality diagnostic: p value significance conflict.

Oral Semaglutide Reduces Heart Failure Events in Diabetes

Participants receiving semaglutide in the SUSTAIN 6 trial.

Individual participant data from participants in the SUSTAIN 6 (N = 3297) and PIONEER 6 (N = 3183) CVOTs, receiving semaglutide (SUSTAIN 6: OW s.c. 0.5 or 1.0 mg; PIONEER 6: OD oral 14 mg) or placebo, were used in this analysis.

Participants receiving placebo in the SUSTAIN 6 and PIONEER 6 trials.

Data from the s.c. and oral semaglutide arms were pooled and compared with pooled placebo data from both trials.

Semaglutide improves cardiorenal outcomes in high-risk diabetes patients

Placebo Group

Participants received subcutaneous semaglutide 1.0 mg once weekly.

Semaglutide Group

Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo.

Participants received matching placebo once weekly.

Semaglutide improves kidney and cardiovascular outcomes in diabetes

Participants received weekly injectable semaglutide 2.4 mg.

Semaglutide 2.4 mg

In SELECT, people with overweight or obesity and atherosclerotic cardiovascular disease without diabetes were randomized to weekly semaglutide 2.4 mg or placebo.

Semaglutide may reduce cardiovascular events in non-diabetic patients.

Participants received semaglutide to evaluate cardiovascular, metabolic, and safety outcomes.

In SUSTAIN 6, participants received OW s.c. semaglutide 0.5 mg or 1.0 mg (median follow-up of 2 years), while in PIONEER 6, participants received OD oral semaglutide 14 mg (median observation time of 15.9 months).

Participants received a dose-matched placebo as a comparator to semaglutide.

In both trials, the comparator was dose-matched placebo and treatments were in addition to standard of care.

Semaglutide reduces cardiovascular events and body weight in T2D

Structured population data were available for 4 of 4 supporting studies. 3 studies described participants with type 2 diabetes. 4 studies described adult participants.

Upstream consistency scoring indicates mixed findings across the evidence.

1 supporting study does not have a displayable topic-matched quantitative effect.

2 supporting studies have high, serious, critical, unclear, or unavailable risk-of-bias information.

Structured population data were available for 3 of 3 supporting studies. 1 study described participants with type 2 diabetes. 3 studies described adult participants.

2 of 3 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 6 of 6 supporting studies. 4 studies described participants with type 2 diabetes. 6 studies described adult participants.

1 supporting study has high, serious, critical, unclear, or unavailable risk-of-bias information.

Structured population data were available for 3 of 3 supporting studies. 3 studies described participants with type 2 diabetes. 3 studies described adult participants.

Semaglutide

Evidence signal

Evidence snapshot

Clinical conclusion

Observed effects

Absolute change

Evidence composition

Consistency

Population and applicability

Limitations

Supporting evidence