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Mounjaro ® (tirzepatide) injection
2.5 mg/5 mg/7.5 mg/10 mg/12.5 mg/15 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What were the results of the analysis on the composite endpoints across the SURPASS-1 to -5 clinical trials in patients with type 2 diabetes?
Across the SURPASS-1 to -5 clinical trials, more tirzepatide-treated participants with T2D achieved clinically meaningful composite endpoints, than those in the comparator groups.
See important safety information, including boxed warning, in the attached prescribing information.
Triple Endpoint
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 proportion of participants achieving the composite endpoint glycated hemoglobin (HbA1c) (<7.0%, ≤6.5%, or <5.7%) with weight loss (≥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
Compared to those who received placebo, semaglutide 1 mg or basal insulin, significantly more tirzepatide-treated patients achieved clinically meaningful composite endpoints, which included an HbA1c value of <7.0%, ≤6.5%, or <5.7% with ≥5%, ≥10%, or ≥15% weight loss and without hypoglycemia (Proportions of Participants Achieving an HbA1c <5.7%, With ≥5% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c <5.7%, With ≥10% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c <5.7%, With ≥15% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c <6.5%, With ≥5% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c ≤6.5%, With ≥10% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c ≤6.5%, With ≥15% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c <7.0%, With ≥5% Weight Loss, and Without Hypoglycemia, Proportions of Participants Achieving an HbA1c <7.0%, With ≥10% Weight Loss, and Without Hypoglycemia, and Proportions of Participants Achieving an HbA1c <7.0%, With ≥15% Weight Loss, and Without Hypoglycemia).2
Figure description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <5.7%, with ≥5% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <5.7%, with ≥10% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <5.7%, with ≥15% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <6.5%, with ≥5% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS 1-5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <6.5%, with ≥10% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint (HbA1c <6.5%, with ≥15% weight loss, and without hypoglycemia) compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite (HbA1c <7.0%, with ≥5% weight loss, and without hypoglycemia) endpoint compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite endpoint compared with placebo or active comparators in SURPASS-1 to -5.
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 description: Significantly more participants treated with any dose of tirzepatide achieved the composite (HbA1c <7.0%, with ≥15% weight loss, and without hypoglycemia) endpoint compared with placebo or active comparators in SURPASS-1 to -5.
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
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1Mounjaro [package insert]. Indianapolis, IN: Eli Lilly and Company; 2022.
2Lingvay 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
3Lingvay 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. Published online December 13, 2022. https://doi.org/10.1111/dom.14943
Date of Last Review: February 10, 2023