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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.
Can Mounjaro® (tirzepatide) be used to treat latent autoimmune diabetes in adults (LADA)?
No clinical trials have been conducted to evaluate tirzepatide for the treatment of people with LADA. In a post hoc analysis of SURPASS-2 to -5 trials, tirzepatide reduced HbA1c and body weight irrespective of GADA status in adults with type 2 diabetes.
See important safety information, including boxed warning, in the attached prescribing information.
Latent Autoimmune Diabetes in Adults
Tirzepatide is not indicated to treat latent autoimmune diabetes in adults (LADA), also known as type 1.5 diabetes.1
Currently, Eli Lilly and Company does not have any planned tirzepatide clinical trials in people with LADA.
Post Hoc Analysis – GADA-Positive Versus GADA-Negative Patients in SURPASS-2 to -5 Trials
Patients with type 2 diabetes (T2D) who test positive for glutamic acid decarboxylase autoantibodies (GADAs) are considered to have LADA.2
A post hoc analysis of SURPASS-2 through -5 evaluated the effect of tirzepatide on glycated hemoglobin (HbA1c) and body weight in people with T2D who were GADA-positive versus those who were GADA-negative. Patients were categorized as GADA-positive if they had GADA concentrations ≥5 IU/mL as detected by ELISA assay.2
There were 3827 tirzepatide-treated patients from SURPASS-2 to -5 who were tested for GADA. Of those with available data,
- 3671 (96.8%) were GADA-negative, and
- 120 (3.2%) were GADA-positive.2
Baseline characteristics were similar between the GADA-positive and GADA-negative groups, with the exception of baseline body mass index (BMI) and serum triglycerides, which were slightly lower in the GADA-positive group.2
Tirzepatide Efficacy Based on GADA Status
At week 40/42, both GADA-positive and GADA-negative patients experienced significant reductions from baseline in
- HbA1c (p<.001), and
- body weight (p<.001).2
Reductions in HbA1c at week 40/42 were significantly greater (p=.024) in the GADA-negative patients than the GADA-positive patients (p=.024) ().2
Parameterb |
GADA-Positive |
GADA-Negative |
Change in HbA1c, % |
-2.11 |
-2.32 |
P value versus baseline |
<.001 |
<.001 |
ETD (95% CI)c |
0.21 (0.03, 0.39); p=0.024 |
|
Change in body weight, kg |
-9.22 |
-9.60 |
P value versus baseline |
<.001 |
<.001 |
ETD (95% CI)c |
0.38 (-0.99, 1.75); p=0.588 |
Abbreviations: BMI = body mass index; ETD = estimated treatment difference; GADA = glutamic acid decarboxylase autoantibodies; HbA1c = glycated hemoglobin; LSM = least squares mean; MMRM = mixed-effects model for repeated measures.
Note: Analyses used the efficacy analysis set, which included all randomized patients who took at least one dose of study drug, excluding patients who discontinued study drug due to inadvertent enrollment and excluding data after initiation of rescue medication or premature discontinuation of study drug. MMRM was adjusted for baseline covariates including study, sex, HbA1c, and BMI.
aSURPASS-2, -3, and -5 had measurements at week 40; SURPASS-4 had measurements at week 42.
bData are LSM change from baseline.
cGADA-negative group versus GADA-positive group.
Efficacy Based on Baseline C-peptide Level
Fasting connecting peptide (C-peptide) levels have been used to assess beta-cell function in patients with LADA, and guide therapeutic decisions, including the potential need for insulin therapy.3-7
For this reason, the effect of tirzepatide on glycemic control was evaluated based on baseline fasting C-peptide levels in GADA-positive patients from SURPASS-2 and SURPASS-4.2
The baseline fasting C-peptide level subgroups selected for this analysis were based on C-peptide categories outlined in the consensus statement from 2020 on the management of LADA from an international expert panel.7
The GADA-positive, tirzepatide-treated patients experienced reductions in HbA1c at primary endpoint irrespective of their fasting baseline C-peptide level ().2
Baseline C-peptide Subgroup |
Number of Participantsa |
Baseline C-peptide, nmol/Lb |
|
<0.3 nmol/L |
10 |
0.19 (0.1, 0.3) |
-2.00 (-2.9, 0.9) |
≥0.3 to ≤0.7 nmol/L |
22 |
0.54 (0.3, 0.7) |
-2.40 (-4.1, -0.1) |
>0.7 nmol/L |
32 |
1.09 (0.7, 2.8) |
-2.15 (-4.9, -0.5) |
Abbreviations: GADA = glutamic acid decarboxylase autoantibody; HbA1c = glycated hemoglobin; TZP = tirzepatide.
Note: C-peptide cut-offs are based on the current guidelines for management of LADA.7
aPopulation consisted of GADA-positive patients treated with TZP from SURPASS-2 and SURPASS-4.
bData are median (min, max).
cSURPASS-2 primary endpoint was 40 weeks. SURPASS-4 primary endpoint was 52 weeks.
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.
2Peters AL, Buzzetti R, Lee CJE, et al. Effect of tirzepatide in GADA-positive individuals with T2D: a post hoc analysis of the SURPASS 2-5 trials. Poster presented at: The 105th Annual Meeting of the Endocrine Society (ENDO); June 15-18, 2023; Chicago, IL.
3Liu L, Li X, Xiang Y, et al. Latent autoimmune diabetes in adults with low-titer GAD antibodies: similar disease progression with type 2 diabetes: a nationwide, multicenter prospective study (LADA China Study 3). Diabetes Care. 2015;38(1):16-21. https://doi.org/10.2337/dc14-1770
4Davis AK, DuBose SN, Haller MJ, et al; T1D Exchange Clinic Network. Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 2015;38(3):476-481. https://doi.org/10.2337/dc14-1952
5Pipi E, Marketou M, Tsirogianni A. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus. World J Diabetes. 2014;5(4):505-510. https://doi.org/10.4239/wjd.v5.i4.505
6Hernandez M, Mollo A, Marsal JR, et al; Action LADA consortium. Insulin secretion in patients with latent autoimmune diabetes (LADA): half way between type 1 and type 2 diabetes: action LADA 9. BMC Endocr Disord. 2015;15:1. https://doi.org/10.1186/1472-6823-15-1
7Buzzetti R, Tuomi T, Mauricio D, et al. Management of latent autoimmune diabetes in adults: a consensus statement from an international expert panel. Diabetes. 2020;69(10):2037-2047. https://doi.org/10.2337/dbi20-0017
8Frías JP, Davies MJ, Rosenstock J, et al; SURPASS-2 Investigators. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. https://doi.org/10.1056/NEJMoa2107519
9Del Prato S, Kahn SE, Pavo I, et al; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021;398(10313):1811-1824. https://doi.org/10.1016/S0140-6736(21)02188-7
Date of Last Review: April 21, 2023