Achieving Normoglycemia With Tirzepatide: Analysis of SURPASS 1–4 Trials
Open accessAbstract
OBJECTIVE: Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health. RESEARCH DESIGN AND METHODS: Baseline characteristics and change from baseline to week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (<5.7%, 5.7–6.5%, and >6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1–4 trials (N = 3,229). Logistic regression models with tirzepatide doses adjusted as a covariate were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c <5.7%. RESULTS: Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with those who did not achieve HbA1c <5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk. CONCLUSIONS: Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.
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The only episodes of clinically significant hypoglycaemia with tirzepatide were reported for up to 2% of participants who received it as add-on to sulphonylurea or basal insulin.
“The only episodes of clinically significant hypoglycaemia with tirzepatide were reported for up to 2% of participants who received it as add-on to sulphonylurea or basal insulin [64].”
From Recent advances in peptide-based therapies for obesity and type 2 diabetes (2024) · cites this paper as [64]
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Recent advances in peptide-based therapies for obesity and type 2 diabetes
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- Authors
- Rosenstock, J., Vázquez, L., Del Prato, S., Franco, D. R., Weerakkody, G., Dai, B., Landó, L. F., Bergman, B. K., & Rodríguez, A.
- Affiliations
- Velocity Clinical Research (United States) (US)
- Marqués de Valdecilla University Hospital (ES)
- 3Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- DASA (Brazil) (BR)
- Eli Lilly (United States) (US)
- 5Eli Lilly and Co., Indianapolis, IN
- Corresponding author
- Rosenstock, Julio
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2023-09-06
- Volume
- 46
- Issue
- 11
- Pages
- 1986-1992
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC10620542
- OpenAlex
- W4386471316
- Cited by
- 45
- References
- 18
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 13
- FWCI
- 9.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- tirzepatide, normoglycemia, HbA1c, type 2 diabetes, GIP/GLP-1 receptor agonist, SURPASS trials, glycemic control, weight loss, cardiometabolic health, hypoglycemia risk, blood pressure, liver enzymes, lipid parameters, waist circumference
- MeSH terms
- Tirzepatide, Blood Pressure, Body Weight, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents
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