Structured population data were available for 12 of 12 supporting studies. Diabetes type was heterogeneous: 9 studies with type 2 diabetes, 1 studies with type 1 diabetes. 12 studies described adult participants.

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

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

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

9 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.

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

Available source content was suppressed because validation identified a conflict.

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

Semaglutide 1 mg

Participants receiving tirzepatide in the SURPASS studies.

Tirzepatide

The difference in mean HbA1c change from baseline at 40 weeks (total effect) between tirzepatide and the placebo group ranged from -20.0 to -14.6 mmol/mol, and that between tirzepatide and semaglutide (1 mg) ranged from -5.1 to -1.9 mmol/mol.

Participants receiving placebo in the SURPASS studies.

In the placebo-controlled trials, 12%-27% of the difference in HbA1c change between tirzepatide dose arms and placebo was estimated as being mediated through WL when given as monotherapy (S1).

Participants receiving semaglutide 1 mg in the SURPASS studies.

Compared with semaglutide, 54%-71% of the difference in HbA1c change between tirzepatide and semaglutide was estimated as being WL-D.

Tirzepatide improves HbA1c via weight loss in type 2 diabetes.

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.

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: p value significance conflict.

Authoritative quality diagnostic: source evidence unresolved.

Tirzepatide improves weight loss in type 1 diabetes and obesity

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

Tirzepatide plus Low-Calorie Diet (LCD)

Participants received tirzepatide alongside a low-energy ketogenic diet.

Tirzepatide plus Low-Energy Ketogenic Diet (LEKT)

Participants were assigned to the dietary arm deemed most appropriate for their clinical and behavioral profile. One group received TZP plus LEKT (n = 30).

Participants received tirzepatide alongside a conventional low-calorie diet.

The other group received TZP plus LCD (n = 30).

Tirzepatide with Ketogenic Diet Improves Liver Health

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

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.

Evidence uses heterogeneous comparison contexts: active_comparator, usual_care.

Structured population data were available for 8 of 8 supporting studies. 4 studies described participants with type 2 diabetes. 8 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: baseline_within_group, unknown_unresolved, usual_care.

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

Evidence uses heterogeneous comparison contexts: baseline_within_group, usual_care.

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

Evidence uses heterogeneous comparison contexts: active_comparator, unknown_unresolved.

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. 4 studies described participants with type 2 diabetes. 4 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. Diabetes type was heterogeneous: 2 studies with type 1 diabetes, 1 studies with type 2 diabetes. Age groups were heterogeneous: 2 studies with adult participants, 1 studies with youth participants.

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

4 of 5 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 10 of 11 supporting studies. Diabetes type was heterogeneous: 5 studies with type 2 diabetes, 2 studies with type 1 diabetes. 8 studies described adult participants.

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

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

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

1 supporting study lacks usable structured population information.

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

Structured population data were available for 8 of 8 supporting studies. 7 studies described participants with type 2 diabetes. 7 studies described adult participants.

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

1 supporting study has 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 1 diabetes. 2 studies described adult participants.

Structured population data were available for 8 of 8 supporting studies. 6 studies described participants with type 2 diabetes. 7 studies described adult participants.

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

Structured population data were available for 8 of 8 supporting studies. Diabetes type was heterogeneous: 4 studies with type 2 diabetes, 1 studies with type 1 diabetes. Age groups were heterogeneous: 4 studies with adult participants, 1 studies with youth participants.

5 of 8 studies with duration data have follow-up of 12 weeks or less.

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

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

Evidence uses heterogeneous comparison contexts: active_comparator, placebo.

Evidence uses heterogeneous comparison contexts: active_comparator, baseline_within_group.

Structured population data were available for 3 of 3 supporting studies. Diabetes type was heterogeneous: 1 studies with type 1 diabetes, 1 studies with type 2 diabetes. 2 studies described adult participants.

Structured population data were available for 13 of 13 supporting studies. 11 studies described participants with type 2 diabetes. 12 studies described adult participants.

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

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

Evidence uses heterogeneous comparison contexts: unknown_unresolved, usual_care.

Structured population data were available for 3 of 3 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. Age groups were heterogeneous: 2 studies with adult participants, 1 studies with youth participants.

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

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

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

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

Structured population data were available for 10 of 10 supporting studies. Diabetes type was heterogeneous: 8 studies with type 2 diabetes, 2 studies with type 1 diabetes. Age groups were heterogeneous: 8 studies with adult participants, 1 studies with youth participants.

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

3 studies contain conflicting p-value and significance fields; those significance claims are suppressed.

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

Evidence uses heterogeneous comparison contexts: other, usual_care.

2 of 4 studies with duration data have follow-up of 12 weeks or less.

Structured population data were available for 4 of 4 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. 4 studies described adult participants.

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

Structured population data were available for 11 of 11 supporting studies. 10 studies described participants with type 2 diabetes. 11 studies described adult participants.

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

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

Structured population data were available for 7 of 7 supporting studies. Diabetes type was heterogeneous: 2 studies with type 2 diabetes, 1 studies with type 1 diabetes. 5 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. 3 studies described participants with type 2 diabetes. 4 studies described adult participants.

Structured population data were available for 5 of 5 supporting studies. Diabetes type was heterogeneous: 4 studies with type 2 diabetes, 1 studies with type 1 diabetes. 3 studies described adult participants.

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

Tirzepatide

Evidence signal

Evidence snapshot

Clinical conclusion

Observed effects

Absolute change

Absolute change

Mean difference

Mean difference

Mean difference

Evidence composition

Consistency

Population and applicability

Limitations

Supporting evidence

Evidence signal

Evidence snapshot

Clinical conclusion

Observed effects

Absolute change

Absolute change

Mean difference

Mean difference

Mean difference

Evidence composition

Consistency

Population and applicability

Limitations

Related evidence

Supporting evidence