What were the results of the analysis on the composite endpoints across the SURPASS-1 to -5 clinical trials in participants with type 2 diabetes?

See important safety information, including boxed warning, in the attached prescribing information.

Composite Endpoint in the Tirzepatide Type 2 Diabetes Studies

Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D) for once-weekly, subcutaneous administration.¹

This post hoc analysis of SURPASS-1 to -5 compared the proportion of participants at the composite endpoint glycated hemoglobin (HbA1c) (<7.0%, ≤6.5%, or <5.7%) with weight reduction (≥5%, ≥10%, or ≥15%) and without hypoglycemia for each of the tirzepatide treatment groups (5, 10, or 15 mg) compared with their respective comparator groups (at week 40 or 52) using the efficacy analysis dataset.² 

Results from each of the endpoints of the HbA1c value of <7.0%, ≤6.5%, or <5.7% with ≥5%, ≥10%, or ≥15% weight reduction and without hypoglycemia are presented in Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, and Figure 9.²

Figure 1. Proportions of Participants with an HbA1c <5.7%, With ≥5% Weight Reduction, and Without Hypoglycemia²

Figure 1 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c less than 5.7% with 5% or more weight loss and without hypoglycemia ranged from 16% to 51% across tirzepatide doses (SURPASS-1 to -5), 1% with placebo (SURPASS-1 and -5), 15% with semaglutide 1 mg (SUPASS-2), and 1-2% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 2. Proportions of Participants with an HbA1c <5.7%, With ≥10% Weight Reduction, and Without Hypoglycemia²

Figure 2 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than 5.7% with 10% or more weight loss and without hypoglycemia ranged from 9% to 41% across tirzepatide doses (SURPASS-1 to -5), 0% with placebo (SURPASS-1 and -5), 9% with semaglutide 1 mg (SURPASS-2), and less than 1% to 1% with basal insulin (SURPASS-3 and -4). 

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 3. Proportions of Participants With an HbA1c <5.7%, With ≥15% Weight Reduction, and Without Hypoglycemia²

Figure 3 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than 5.7% with 15% or more weight loss and without hypoglycemia ranged from 5% to 29% across tirzepatide doses (SURPASS-1 to -5), 0% with placebo (SURPASS-1 and -5), 3% with semaglutide 1 mg (SURPASS-2), and 0 to less than 1% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 4. Proportions of Participants With an HbA1c <6.5%, With ≥5% Weight Reduction, and Without Hypoglycemia²

Figure 4 description: After 40 or 52 weeks of treament, the proportions of participants having an HbA1c value of less than or equal to 6.5% with 5% or more weight loss and without hypoglycemia ranged from 38% to 78% across tirzepatide doses (SURPASS-1 to -5), 3% with placebo (SURPASS-1 and -5), 45% with semaglutide 1 mg (SURPASS-2), and 3-4% with basal insulin (SURPASS-3 and -4). 

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 5. Proportions of Participants With an HbA1c ≤6.5%, With ≥10% Weight Reduction, and Without Hypoglycemia²

Figure 5 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than or equal to 6.5% with 10% or more weight loss and without hypoglycemia ranged from 16% to 64% across tirzepatide doses (SURPASS-1 to -5), 0-1% with placebo (SURPASS-1 and -5), 22% with semaglutide 1 mg (SURPASS-2), and 1-3% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 6. Proportions of Participants With an HbA1c ≤6.5%, With ≥15% Weight Reduction, and Without Hypoglycemia²

Figure 6 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than or equal to 6.5% with 15% or more weight loss and without hypoglycemia ranged from 6% to 40% across tirzepatide doses (SURPASS-1 to -5), 0% with placebo (SURPASS-1 and -5), 7% with semaglutide 1 mg (SURPASS-2), and 0 to less than 1% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 7. Proportions of Participants With an HbA1c <7.0%, With ≥5% Weight Reduction, and Without Hypoglycemia²

Figure 7 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than 7% with 5% or more weight loss and without hypoglycemia ranged from 43% to 82% across tirzepatide groups (SURPASS-1 to -5), 4-5% with placebo (SURPASS-1 and -5), 51% with semaglutide 1 mg (SURPASS-2), and 5% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 8. Proportions of Participants With an HbA1c <7.0%, With ≥10% Weight Reduction, and Without Hypoglycemia²

Figure 8 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than 7% with 10% or more weight loss and without hypoglycemia ranged from 17% to 66% across tirzepatide doses (SURPASS-1 to -5), 0-1% with placebo (SURPASS-1 and -5), 25% with semaglutide 1 mg (SURPASS-2), and 1-3% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Figure 9. Proportions of Participants With an HbA1c <7.0%, With ≥15% Weight Reduction, and Without Hypoglycemia²

Figure 9 description: After 40 or 52 weeks of treatment, the proportions of participants having an HbA1c value of less than 7% with 15% or more weight loss and without hypoglycemia ranged from 6% to 42% across tirzepatide doses (SURPASS-1 to -5), 0% with placebo (SURPASS-1 and -5), 8% with semaglutide 1 mg (SURPASS-2), and 0 to less than 1% with basal insulin (SURPASS-3 and -4).

Abbreviations: HbA1c = glycated hemoglobin; MET = metformin; N = number of subjects in imputed data; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; SU = sulfonylurea; wk = week.

Note: HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS-1, -2, -5) or week 52 (SURPASS-3, -4). Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. A logistic regression model using imputed data with baseline HbA1c value, baseline weight, pooled country, and treatment as factors was used in each study to compare treatment arms.

*p<.05 versus comparator arm.

**p<.001 versus comparator arm. 

Enclosed Prescribing Information

MOUNJARO® (tirzepatide) injection, for subcutaneous use, Lilly

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1. Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2025.

2. Lingvay I, Cheng AYY, Levine JA, et al. Achievement of glycaemic targets with weight loss and without hypoglycaemia in type 2 diabetes with the once-weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide: a post hoc analysis of the SURPASS-1 to -5 studies. Diabetes Obes Metab. 2023;25(4):965-974. https://doi.org/10.1111/dom.14943