What is the effect of Mounjaro® (tirzepatide) on fasting serum glucose?

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

Fasting Serum Glucose 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

In SURPASS-1 to -6, changes in fasting serum glucose (FSG) from baseline were assessed in adults with T2D treated with tirzepatide 5, 10, and 15 mg, placebo, semaglutide 1 mg, titrated insulin degludec, titrated insulin glargine, and titrated insulin lispro (Table 1).^2-7

Two statistical estimands, efficacy or treatment-regimen, were used to evaluate efficacy data from the phase 3 clinical trials of tirzepatide.^2-7

In the SURPASS clinical trial program, the

• efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug, and 

• treatment-regimen estimand evaluates the treatment effect irrespective of adherence to the study drug.^2-7

Differences in reported data may reflect the application of these estimands. This response presents data reflecting the efficacy estimand. For treatment-regimen estimand results, please refer to the manuscript cited and/or the US prescribing information, where applicable.^1-7

Table 1. Summary of Fasting Serum Glucose in SURPASS Studies^2-8

FSG, mg/dLa	Tirzepatide 5 mg	Tirzepatide 10 mg	Tirzepatide 15 mg	Comparatorb
SURPASS-1
FSG at baseline	153.7±3.7	152.6±3.7	154.6±3.7	155.2±3.8
FSG change from baseline	-43.6±3.4	-45.9±3.5	-49.3±3.6	12.9±4.0
Difference vs placeboc	-56.5 (-66.8, -46.1)***	-58.8 (-69.2, -48.4)***	-62.1 (-72.7, -51.5)***	--
SURPASS-2
FSG at baseline	174.2±2.39	174.6±2.40	172.3±2.39	170.9±2.40
FSG change from baseline	-56.0±1.57	-61.6±1.60	-63.4±1.59	-48.6±1.58
Difference vs semaglutided	-7.3 (-11.7, -3.0)**	-13.0 (-17.4, -8.6)***	-14.7 (-19.1, -10.3)***	--
SURPASS-3
FSG at baseline	171.8±2.44	170.7±2.44	168.4±2.44	166.4±2.44
FSG change from baseline	-48.2±1.82	-54.8±1.86	-59.2±1.85	-55.7±1.81
Difference vs insulin degludecd	7.5 (2.4, 12.5)**	0.8 (-4.3, 5.9)	-3.6 (-8.7, 1.5)	--
SURPASS-4
FSG at baseline	172.3±2.81	175.7±2.84	174.2±2.78	168.7±1.62
FSG change from baseline	-50.4±2.07	-54.9±2.06	-59.3±2.04	-51.4±1.17
Difference vs insulin glargined	1.0 (-3.7, 5.7)	-3.6 (-8.2, 1.1)	-8.0 (-12.6, -3.4)***	--
SURPASS-5
FSG at baseline	162.2±4.81	162.9±4.79	160.4±4.75	164.4±4.75
FSG change from baseline	-61.4±2.55	-67.9±2.55	-67.7±2.64	-38.9±2.49
Difference vs placeboc	-22.5 (-29.5, -15.4)***	-29.0 (-36.0, -22.0)***	-28.8 (-35.9, -21.6)***	--
SURPASS-6
FSG at baseline	163.4±3.61	155.6±3.65	156.4±3.67	156.0±2.13
FSG change from baseline	-33.2±3.28	-43.0±3.32	-41.6±3.42	-10.0±1.99
Difference vs insulin lisprod	-23.2 (-30.8, -15.7)***	-33.0 (-40.6, -25.4)***	-31.6 (-39.3, -23.8)***	--

Abbreviations: FSG = fasting serum glucose; LSM = least squares mean; mITT = modified intention-to-treat; MMRM = mixed model repeated measures.

Efficacy estimand evaluates the treatment effect prior to discontinuation of the study drug without confounding effects of antihyperglycemic rescue therapy. Analyzed by MMRM using the mITT population (efficacy analysis set).

 **p<.01, and ***p<.001 versus comparator. 

^a Data are LSM±SE at baseline and change from baseline at endpoint and treatment differences are LSM (95% CI).

^b Comparator was placebo in SURPASS-1 and SURPASS-5 for 40 weeks. Comparator was semaglutide 1 mg once weekly in SURPASS-2 for 40 weeks. Comparator was titrated insulin degludec in SURPASS-3 for 52 weeks. Comparator was titrated insulin glargine in SURPASS-4 for 52 weeks. Comparator was titrated insulin lispro in SURPASS-6 for 52 weeks.

^c Tested for superiority, controlled for type 1 error.

^d Not controlled for type 1 error.

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. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398(10295):143-155. https://doi.org/10.1016/S0140-6736%2821%2901324-6

3. Frías 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

4. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021;398(10300):583-598. https://doi.org/10.1016/S0140-6736(21)01443-4

5. Del 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

6. Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545. https://doi.org/10.1001/jama.2022.0078

7. Rosenstock J, Frías JP, Rodbard HW, et al. Tirzepatide vs insulin lispro added to basal insulin in type 2 diabetes: the SURPASS-6 randomized clinical trial. JAMA. 2023;330(17):1631-1640. https://doi.org/10.1001/jama.2023.20294

8. Data on file, Eli Lilly and Company and/or one of its subsidiaries.