GIP Does Not Potentiate the Antidiabetic Effects of GLP-1 in Hyperglycemic Patients With Type 2 Diabetes
Open accessAbstract
OBJECTIVE: The incretin glucagon-like peptide 1 (GLP-1) exerts insulinotropic activity in type 2 diabetic patients, whereas glucose-dependent insulinotropic polypeptide (GIP) no longer does. We studied whether GIP can alter the insulinotropic or glucagonostatic activity of GLP-1 in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Twelve patients with type 2 diabetes (nine men and three women; 61 ± 10 years; BMI 30.0 ± 3.7 kg/m2; HbA1c 7.3 ± 1.5%) were studied. In randomized order, intravenous infusions of GLP-1(7-36)-amide (1.2 pmol · kg−1 · min−1), GIP (4 pmol · kg−1 · min−1), GLP-1 plus GIP, and placebo were administered over 360 min after an overnight fast (≥1 day wash-out period between experiments). Capillary blood glucose, plasma insulin, C-peptide, glucagon, GIP, GLP-1, and free fatty acids (FFA) were determined. RESULTS: Exogenous GLP-1 alone reduced glycemia from 10.3 to 5.1 ± 0.2 mmol/L. Insulin secretion was stimulated (insulin, C-peptide, P < 0.0001), and glucagon was suppressed (P = 0.009). With GIP alone, glucose was lowered slightly (P = 0.0021); insulin and C-peptide were stimulated to a lesser degree than with GLP-1 (P < 0.001). Adding GIP to GLP-1 did not further enhance the insulinotropic activity of GLP-1 (insulin, P = 0.90; C-peptide, P = 0.85). Rather, the suppression of glucagon elicited by GLP-1 was antagonized by the addition of GIP (P = 0.008). FFA were suppressed by GLP-1 (P < 0.0001) and hardly affected by GIP (P = 0.07). CONCLUSIONS: GIP is unable to further amplify the insulinotropic and glucose-lowering effects of GLP-1 in type 2 diabetes. Rather, the suppression of glucagon by GLP-1 is antagonized by GIP.
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GLP-1 has therapeutic potential for reducing elevated plasma glucose and body weight, while GIP is unable to stimulate insulin secretion or lower plasma glucose effectively in T2D.
“Among the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), the latter has been established as having therapeutic potential for reducing elevated plasma glucose (1, 2) and body weight (3), while the former has been unable to either stimulate insulin secretion (1) or lower plasma glucose effectively in type 2 diabetes (T2D) (4).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [4]
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Self-citation
- Authors
- Mentis, N., Vardarli, I., Köthe, L. D., Holst, J. J., Deacon, C. F., Theodorakis, M., Meier, J. J., & Nauck, M. A.
- Affiliations
- Diabeteszentrum Bad Lauterberg (DE)
- University of Copenhagen (DK)
- National and Kapodistrian University of Athens (GR)
- St. Josef-Hospital (DE)
- Corresponding author
- Nauck, Michael A.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2011-03-22
- Volume
- 60
- Issue
- 4
- Pages
- 1270-1276
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC3064100
- OpenAlex
- W2110914062
- Cited by
- 197
- References
- 58
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 19 · 2023: 16 · 2022: 16 · 2021: 22 · 2020: 13 · 2019: 11 · 2018: 8 · 2017: 8 · 2016: 16 · 2015: 11 · 2014: 8 · 2013: 11 · 2012: 8
- FWCI
- 8.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, type 2 diabetes, hyperglycemia, insulin secretion, glucagon suppression, free fatty acids, C-peptide, glucose-lowering effect, incretin-based therapy, insulinotropic effect
- MeSH terms
- Adult, Aged, Diabetes Mellitus, Type 2, Drug Interactions, Female, Gastric Inhibitory Polypeptide, Humans, Hyperglycemia, Hypoglycemic Agents, Male, Middle Aged, Glucagon-Like Peptide 1, Incretins
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