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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 information is available on switching to Mounjaro® (tirzepatide) from a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of type 2 diabetes?
In SURPASS-SWITCH-2, participants with T2D who switched from a GLP-1 RA to tirzepatide 5 mg experienced improved glycemic control and additional weight reduction over 12 weeks. Mild or moderate gastrointestinal AEs were reported by 13.2% of participants.
See important safety information, including boxed warning, in the attached prescribing information.
Prescribing Information Related to Dosing
Mounjaro (tirzepatide) is a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) 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
The recommended starting dose of tirzepatide is 2.5 mg injected subcutaneously once weekly. The 2.5 mg dosage is for treatment initiation and is not intended for glycemic control.1
After 4 weeks, increase the dose to 5 mg once weekly. If additional glycemic control is needed, increase the dosage in 2.5 mg increments after at least 4 weeks on the current dose. The maximum dosage of tirzepatide is 15 mg once weekly.1
Switching From a GLP-1 RA
Switching from a GLP-1 RA to tirzepatide is being evaluated in 2 phase 4 studies in adults with T2D including
Results from SURPASS-SWITCH-2 are available at this time and are described in this response.
Overview of SURPASS-SWITCH-2 Study
SURPASS-SWITCH-2 is a phase 4 clinical trial that evaluates glycemic outcomes, body weight, and adverse events (AEs) that occur in the first 12 weeks following a switch from a GLP-1 RA directly to tirzepatide 5 mg, omitting the 2.5 mg initiation dose.4
Participants in this study had T2D and were on a stable dose of either semaglutide, dulaglutide, or liraglutide prior to enrollment into the trial.4
SURPASS-SWITCH-2 was an open-label, single-arm, multicenter trial in the United States. A control arm was omitted from the study design since the short 12-week duration would not provide adequate insight into comparative efficacy and for additional operational efficiency.4,5
Key Inclusion and Exclusion Criteria
Key inclusion and exclusion criteria are presented in SURPASS-SWITCH-2 Phase 4 Study in Adults With T2D: Key Inclusion and Exclusion Criteria.
Key Inclusion Criteria |
Key Exclusion Criteria |
|
|
|
|
Abbreviations: BMI = body mass index; CHF = congestive heart failure; CV = cardiovascular; GLP-1 = glucagon-like peptide-1; HbA1c = glycated hemoglobin; NYHA = New York Heart Association; OAM = oral antidiabetic medication; RA = receptor agonist; SGLT-2i = sodium-glucose cotransporter-2 inhibitor; T1D = type 1 diabetes; T2D = type 2 diabetes.
aThe OAMs could include metformin, SGLT-2i, thiazolidinediones, or α-glucosidase inhibitors.
Study Design
In SURPASS-SWITCH-2, a total of 152 participants across the United States received treatment with tirzepatide 5 mg once weekly with no dose escalation. Of these, 140 participants were included in efficacy analyses. All participants switched treatment from a prior GLP-1 RA directly to tirzepatide 5 mg. The tirzepatide 2.5 mg initiation dose was omitted (SURPASS-SWITCH-2 Study Design).4
Figure 1 description: SURPASS-SWITCH-2 had 2 study periods. Period 1 consisted of a 3-week screening period, which included a continuous glucose monitoring assessment while participants continued stable dose therapy with their baseline glucagon-like peptide-1 receptor agonist (eg, semaglutide, liraglutide, or dulaglutide). In period 2, participants switched to treatment with tirzepatide 5 mg once weekly, with additional continuous glucose monitoring performed at weeks 4 and 12. The study concluded after 12 weeks of tirzepatide 5 mg treatment. There was no safety follow-up period.
Abbreviations: CGM = continuous glucose monitoring; GLP-1 RA = glucagon-like peptide-1 receptor agonist; QW = once weekly; SC = subcutaneous.
Study Objectives
The primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 12 weeks after switching from a stable dose of GLP-1 RA to tirzepatide 5 mg.4
Secondary endpoints included change from baseline in
- fasting serum glucose (FSG) at week 12
- body weight at week 12, and
- continuous glucose monitoring (CGM)-derived glucose levels time above range (TAR) at weeks 4 and 12.4
Tolerability and safety were also assessed through the reporting of AEs.4
Baseline Characteristics
The baseline characteristics of SURPASS-SWITCH-2 participants who switched from GLP-1 RA to tirzepatide 5 mg are summarized in Baseline Demographics and Characteristics .4
Characteristica |
Study Population |
Age, y |
58.3±10.3 |
Female, n (%) |
77 (55.0) |
Duration of T2D, y |
12.4±7.4 |
Race, n (%) |
|
American Indian or Alaska Native |
2 (1.4) |
Asian |
9 (6.4) |
Black or African American |
21 (15.0) |
White |
108 (77.1) |
HbA1c, % |
7.39±0.66 |
Fasting serum glucose, mg/dL |
140.24±33.25 |
Body mass index, kg/m2 |
35.18±6.74 |
Weight, kg |
100.55±22.60 |
Baseline GLP-1 RA, n (%)c |
|
Semaglutide |
77 (55.0) |
0.5 mg QW |
20 (26.0) |
1.0 mg QW |
39 (50.6) |
2.0 mg QW |
18 (23.4) |
Dulaglutide |
59 (42.1) |
0.75 mg QW |
15 (25.4) |
1.5 mg QW |
21 (35.6) |
3.0 mg QW |
11 (18.6) |
4.5 mg QW |
12 (20.3) |
Liraglutide |
3 (2.1) |
1.2 mg QD |
1 (33.3) |
1.8 mg QD |
2 (66.7) |
Participants with ≥1 concomitant OAM, n (%) |
110 (78.6) |
Metformin |
89 (63.6) |
SGLT-2 inhibitors |
48 (34.3) |
Thiazolidinediones |
12 (8.6) |
Metformin/SGLT-2 inhibitor combination therapy |
5 (3.6) |
Abbreviations: GLP-1 RA = glucagon-like peptide-1 receptor agonist; HbA1c = glycated hemoglobin; OAM = oral antihyperglycemic medication; QD = once daily; QW = once weekly; SGLT-2 = sodium-glucose cotransporter-2; T2D = type 2 diabetes.
aData are presented as mean ± SD unless otherwise noted.
bExcludes inadvertently enrolled participants.
cOne participant had a missing value for the baseline GLP-1 RA.
Efficacy Results
As presented in SURPASS-SWITCH-2 Primary and Secondary Endpoints at Week 12, participants on stable GLP-1 RA doses who switched directly to tirzepatide 5 mg showed significant reductions from baseline to week 12 (p<.001) in
- HbA1c
- FSG
- body weight, and
- TAR (>180 mg/dL by CGM).4
Significant reductions from baseline (p<.001) in HbA1c (Change in HbA1c Over Time After Switching to Tirzepatide 5 mg Based on Prior GLP-1 RA) and weight (Change in Body Weight Over Time After Switching to Tirzepatide 5 mg Based on Prior GLP-1 RA) were also observed in a subgroup analysis of participants who switched to tirzepatide 5 mg from prior stable doses of semaglutide or dulaglutide.6
Parametera |
Tirzepatide 5 mg |
HbA1c, % |
|
Baseline |
7.39 |
Week 12 |
6.96 |
CFB |
-0.43*** |
FSG, mg/dL |
|
Baseline |
140.49 |
Week 12 |
132.85 |
CFB |
-7.83** |
Body weight, kg |
|
Baseline |
100.42 |
Week 12 |
98.27 |
CFB |
-2.15*** |
TAR >180 mg/dL by CGM, % |
|
Baseline |
21.9 |
Week 12 |
14.58 |
CFB |
-7.37*** |
Abbreviations: CFB = change from baseline; CGM = continuous glucose monitoring; FSG = fasting serum glucose; HbA1c = glycated hemoglobin; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures; TAR = time above range.
***p<.001, **p<.01 versus baseline.
Note: Data are from MMRM analysis of mITT population. The efficacy analysis set includes all participants who took at least 1 dose of study drug, excluding participants who were inadvertently enrolled and data after treatment discontinuation.
aData are presented as least squares mean.
Figure 2 description: Participants who switched from stable doses of semaglutide or dulaglutide to tirzepatide 5 mg experienced significant reductions in glycated hemoglobin over 12 weeks (p<.001).
Abbreviations: GLP-1 RA = glucagon-like peptide-1 receptor agonist; HbA1c = glycated hemoglobin; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Notes: Data presented are least squares means ± SE. MMRM analysis, mITT population (efficacy analysis set). Assessment of participants on liraglutide at baseline was performed but n=3, so results are not displayed.
***p<0.001 from baseline.
Figure 3 description: Participants who switched from stable doses of semaglutide or dulaglutide to tirzepatide 5 mg experienced significant reductions in body weight over 12 weeks (p<.001).
Abbreviations: GLP-1 RA = glucagon-like peptide-1 receptor agonist; mITT = modified intention-to-treat; MMRM = mixed-effects model for repeated measures.
Notes: Data presented are least squares mean ± SE. MMRM analysis, mITT population (efficacy analysis set). Assessment of participants on liraglutide at baseline was performed but n=3, so results are not displayed.
***p<0.001 from baseline.
Safety Results
Out of 152 participants included in safety analyses for SURPASS-SWITCH-2, 20 (13.2%) participants reported gastrointestinal AEs. Of these,
- 18 (11.8%) were mild severity, and
- 2 (1.3%) were moderate severity.4
Three (2.0%) participants discontinued tirzepatide due to AEs (SURPASS-SWITCH-2 Treatment-Emergent Adverse Events).4
There were no deaths or events of severe hypoglycemia during the trial. Severe hypoglycemia was defined as altered mental or physical status requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions for the treatment of hypoglycemia.4
Eventsa |
Tirzepatide 5 mg |
Participants with ≥1 TEAE |
54 (35.5) |
Serious AEs |
1 (0.7) |
Deaths |
0 |
AEs leading to treatment discontinuationb |
3 (2.0) |
GI AEs leading to treatment discontinuation |
2 (1.3) |
Participants with GI disorders |
20 (13.2) |
GI disorders with mild severity |
18 (11.8) |
GI disorders with moderate severityc |
2 (1.3) |
Abbreviations: AE = adverse event; GI = gastrointestinal; mITT = modified intention-to-treat; TEAE = treatment-emergent adverse event.
aData are presented as n (%) from the mITT population (safety analysis set).
bTwo participants were considered inadvertently enrolled and had an AE that led to discontinuation.
cOne participant had moderate diarrhea and another had moderate constipation/dyspepsia.
Clinical Use
Eli Lilly and Company cannot provide treatment recommendations on how to switch a patient with T2D from a GLP-1 RA to tirzepatide.
Health care providers should assess and determine the appropriate path for individual patients when they are considering changing medications. SURPASS-SWITCH-2 demonstrated one example of a transition from a stable GLP-1 RA to tirzepatide. It was not designed to inform longer-term outcomes, comparative efficacy or define the optimal transition strategy, as that depends on many individual characteristics.5
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; 2023.
2A study of tirzepatide (LY3298176) in adult participants with type 2 diabetes switching from dulaglutide (SURPASS-SWITCH). ClinicalTrials.gov identifier: NCT05564039. Updated March 7, 2024. Accessed April 2, 2024. https://clinicaltrials.gov/ct2/show/NCT05564039
3A study of tirzepatide (LY3298176) in adults with type 2 diabetes switching from a GLP-1 RA (SURPASS-SWITCH-2). ClinicalTrials.gov identifier: NCT05706506. Updated January 23, 2024. Accessed April 2, 2024. https://www.clinicaltrials.gov/ct2/show/NCT05706506
4Jabbour S, Paik JS, Aleppo G, et al. Switching to tirzepatide 5 mg from GLP-1 RAs: clinical expectations in the first 12 weeks of treatment. Endocr Pract. Published online May 7, 2024. https://doi.org/10.1016/j.eprac.2024.05.005
5Data on file, Eli Lilly and Company and/or one of its subsidiaries.
6Jabbour S, Paik JS, Aleppo G, et al. Switching to tirzepatide 5 mg from GLP-1 RAs: clinical expectations in the first 12 weeks of treatment. Poster presented at: 33rd Annual Meeting of the American Association of Clinical Endocrinology (AACE); May 9-11, 2024; New Orleans, LA.
Date of Last Review: April 02, 2024