Structured population data were available for 11 of 11 supporting studies. Diabetes type was heterogeneous: 9 studies with type 2 diabetes, 1 studies with type 1 diabetes. 11 studies described adult participants.

1 relevant study has unresolved authoritative design evidence and does not contribute to design-specific or RoB-specific claims.

Evidence uses heterogeneous comparison contexts: active_comparator, placebo, usual_care.

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

Tirzepatide Group

Core clinician-reference fields are available or not applicable.

Participants continued with and escalated to dulaglutide.

Dulaglutide Group

Participants were randomly assigned 1:1 to continue with and escalate to dulaglutide 4.5 mg or maximum tolerated dose (MTD).

Participants switched to tirzepatide with escalation.

Participants were randomly assigned 1:1 to switch to tirzepatide with escalation to 15 mg or MTD.

Switching to tirzepatide improves glycemic control and weight in type 2 diabetes

Standard Care

Participants treated with tirzepatide for weight management.

Tirzepatide Treatment

In SURMOUNT-1, 81.8 % of participants treated with tirzepatide (pooled 10 mg/15 mg) shifted at least one BMI category lower.

Participants receiving standard care for obesity management.

The SURMOUNT clinical trials assessed in these analyses were SURMOUNT-1 (NCT04184622) and SURMOUNT-4 (NCT04660643).

Authoritative quality diagnostic: invalid or missing unit.

Authoritative quality diagnostic: invalid or missing value.

Tirzepatide improves cardiometabolic health in obesity.

Insulin Glargine

Tirzepatide 5 mg

Participants were randomised to receive tirzepatide (5, 10, or 15 mg) or insulin glargine.

Participants receiving tirzepatide 10 mg.

Tirzepatide 10 mg

Participants receiving tirzepatide 15 mg.

Tirzepatide 15 mg

Tirzepatide improves glycaemic control and weight in type 2 diabetes

Patients receiving tirzepatide 5 mg for type 2 diabetes management.

A total of 687 patients were included for this subgroup analysis, who received tirzepatide 5 mg (n = 230), tirzepatide 10 mg (n = 228) or tirzepatide 15 mg (n = 229).

Patients receiving tirzepatide 10 mg for type 2 diabetes management.

Patients receiving tirzepatide 15 mg for type 2 diabetes management.

Patients receiving insulin glargine as standard care for type 2 diabetes management.

In the SURPASS-AP-Combo trial, once-weekly tirzepatide was associated with improved glycemic control and weight loss versus insulin glargine.

Tirzepatide improves glycemic control and weight loss in type 2 diabetes

Insulin glargine once daily

Participants received tirzepatide administered once weekly.

Tirzepatide 5, 10, or 15 mg once weekly

Participants were randomized 1:1:1:3 to receive tirzepatide 5, 10, or 15 mg once weekly.

Participants received treat-to-target insulin glargine.

Participants were randomized 1:1:1:3 to receive tirzepatide 5, 10, or 15 mg once weekly or treat-to-target insulin glargine.

Tirzepatide improves glycemic control and weight loss sustainability in type 2 diabetes

Comparator Interventions

Participants received once-weekly tirzepatide treatment.

Participants were randomly assigned to receive once-weekly tirzepatide (5 mg, 10 mg, or 15 mg) or one of the following comparator interventions: semaglutide (1 mg), insulin degludec, or placebo.

Participants received either semaglutide, insulin degludec, or placebo.

Tirzepatide improves glycemic control in early-onset type 2 diabetes

Basal Insulin

Participants receiving tirzepatide 5 mg via subcutaneous injection.

In SURPASS-AP-Combo, 79 of 687 tirzepatide recipients were Korean; 26 received tirzepatide 5 mg.

Participants receiving tirzepatide 10 mg via subcutaneous injection.

In SURPASS-AP-Combo, 79 of 687 tirzepatide recipients were Korean; 26 received tirzepatide 10 mg.

Participants receiving tirzepatide 15 mg via subcutaneous injection.

In SURPASS-AP-Combo, 79 of 687 tirzepatide recipients were Korean; 27 received tirzepatide 15 mg.

Participants receiving once-daily basal insulin.

In SURPASS-AP-Combo, participants were randomised to receive, by subcutaneous injection, once-weekly tirzepatide or once-daily basal insulin.

Tirzepatide improves HbA1c and body weight in Korean adults with T2D

Placebo

Participants received tirzepatide 5 mg once weekly.

Participants ( n = 190) with MASH and stage 2/3 fibrosis were randomly assigned to receive tirzepatide (5, 10, or 15 mg) or placebo once weekly.

Participants received tirzepatide 10 mg once weekly.

Participants received tirzepatide 15 mg once weekly.

Participants received placebo once weekly.

Tirzepatide improves MASH resolution and fibrosis in diabetes patients

Placebo Control

Participants receiving once weekly tirzepatide treatment for type 2 diabetes.

Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188).

Participants receiving placebo treatment.

The primary efficacy measure of HbA1c reduction from baseline was superiority of tirzepatide compared with placebo or noninferiority of tirzepatide compared with active comparators.

Tirzepatide improves weight loss in adults with type 2 diabetes

Source evidence could not be resolved sufficiently for this field.

Not extracted from the authoritative source.

Clinician-reference record is usable with limitations in: design, risk_of_bias.

Participants received once-weekly tirzepatide injections.

Tirzepatide

Participants were randomized to once-weekly subcutaneous tirzepatide (2.5 mg for 4 weeks, 5.0 mg for 8 weeks) or placebo.

Participants received identical-appearing placebo injections.

Participants were randomized to once-weekly tirzepatide 5.0 mg or identical-appearing, volume-matched, placebo saline subcutaneous injection.

Authoritative quality diagnostic: source evidence unresolved.

Tirzepatide improves weight loss in type 1 diabetes and obesity

Semaglutide 1 mg

Participants received 5 mg of Tirzepatide.

In Hispanic or Latino patients, the LSM change from baseline in HbA1c at 40 weeks was -2.11% with tirzepatide 5 mg.

Participants received 10 mg of Tirzepatide.

In Hispanic or Latino patients, the LSM change from baseline in HbA1c at 40 weeks was -2.46% with tirzepatide 10 mg.

Participants received 15 mg of Tirzepatide.

In Hispanic or Latino patients, the LSM change from baseline in HbA1c at 40 weeks was -2.47% with tirzepatide 15 mg.

Participants received 1 mg of Semaglutide.

In Hispanic or Latino patients, the LSM change from baseline in HbA1c at 40 weeks was -1.93% with semaglutide.

Tirzepatide shows greater HbA1c and weight reduction than Semaglutide

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

2 relevant studies have unresolved authoritative design evidence and do not contribute to design-specific or RoB-specific claims.

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

1 supporting study lacks usable structured population information.

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. 3 studies described participants with type 2 diabetes. 3 studies described adult participants.

Evidence uses heterogeneous comparison contexts: baseline_within_group, usual_care.

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

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

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

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

Evidence uses heterogeneous comparison contexts: active_comparator, usual_care.

Structured population data were available for 5 of 5 supporting studies. 3 studies described participants with type 2 diabetes. 5 studies described adult participants.

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

Structured population data were available for 4 of 4 supporting studies. 2 studies described adult participants.

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

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

Evidence uses heterogeneous comparison contexts: baseline_within_group, unknown_unresolved, usual_care.

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

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group.

Structured population data were available for 5 of 5 supporting studies. 4 studies described participants with type 2 diabetes. 4 studies described adult participants.

Evidence uses heterogeneous comparison contexts: active_comparator, placebo.

Evidence uses heterogeneous comparison contexts: unknown_unresolved, usual_care.

Structured population data were available for 9 of 9 supporting studies. 3 studies described participants with type 2 diabetes. 7 studies described adult participants.

Evidence uses heterogeneous comparison contexts: baseline_within_group, other, unknown_unresolved, usual_care.

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

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

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group, placebo.

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

Upstream consistency scoring indicates mixed findings across the evidence.

Evidence uses heterogeneous comparison contexts: placebo, usual_care.

Evidence uses heterogeneous comparison contexts: active_comparator, unknown_unresolved.

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

Structured population data were available for 9 of 9 supporting studies. 9 studies described participants with type 2 diabetes. 9 studies described adult participants.

Tirzepatide

Evidence signal

Evidence snapshot

Clinical conclusion

Observed effects

Absolute change

Evidence composition

Consistency

Population and applicability

Limitations

Supporting evidence