Secretion of glucagon-like peptide-1 in patients with type 2 diabetes mellitus: systematic review and meta-analyses of clinical studies
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Aims/hypothesis We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test.Methods Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied.Results Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes (n = 275) and controls without type 2 diabetes (n = 279) exhibited similar responses of total GLP-1 (p = NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [-2.50, 4.67]), total AUC (tAUC) (159 pmol/l × min [-270, 589]), time-corrected tAUC (tAUC min⁻¹) (0.99 pmol/l [-1.28, 3.27]), incremental AUC (iAUC) (-122 pmol/l × min [-410, 165]) and time-corrected iAUC (iAUC min⁻¹) (-0.49 pmol/l [-2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min⁻¹) and after a 50 g OGTT (AUC and tAUC min⁻¹), and reduced responses after a solid mixed meal test (tAUC min⁻¹) among patients with type 2 diabetes. Meta-regression analyses showed that HbA1c and fasting plasma glucose predicted the outcomes iAUC and iAUC min⁻¹, respectively.Conclusions/interpretation The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion.
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GIP has protective features on β-cell survival, and this has a synergistic effect with GLP-1 in healthy humans, but this mechanism is impaired in those with T2DM.
“It has protective features on the β-cells survival, and this has a synergistic effect with GLP-1 in healthy humans, but this mechanism is impaired in those with T2DM [21,22].”
From The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update. (2024) · cites this paper as [22]
The Introduction and Discussion report a reduced incretin effect in people with type 2 diabetes. They do not establish that GIP protects β-cell survival, that GIP and GLP-1 act synergistically in healthy humans, or that this specific synergy is impaired in type 2 diabetes. Page numbers are unavailable in our copy. (LLM, conf=0.78)
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References 52 · Cited by 251
- Authors
- Calanna, S., Christensen, M., Holst, J. J., Laferrère, B., Gluud, L. L., Vilsbøll, T., & Knop, F. K.
- Affiliations
- University of Copenhagen (DK)
- St. Luke's-Roosevelt Hospital Center (US)
- Corresponding author
- Knop, F. K.
- Venue
- Diabetologia
- Published
- 2013-02-03
- Volume
- 56
- Issue
- 5
- Pages
- 965-972
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC3687347
- OpenAlex
- W2146532684
- Cited by
- 251
- References
- 52
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 21 · 2023: 13 · 2022: 12 · 2021: 19 · 2020: 14 · 2019: 19 · 2018: 19 · 2017: 27 · 2016: 23 · 2015: 25 · 2014: 22 · 2013: 11
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Università di Pisa
- Novo Nordisk Fonden (NNF12OC1015904)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067561, P30DK026687)
- 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
- glucagon-like peptide-1, type 2 diabetes, GLP-1 secretion, oral glucose tolerance test, mixed meal tolerance test, glycemic control, HbA1c, fasting blood glucose, incretin response
- MeSH terms
- Diabetes Mellitus, Type 2, Glucose Tolerance Test, Glycated Hemoglobin, Humans, Hyperglycemia, Intestinal Mucosa, Severity of Illness Index, Down-Regulation, Postprandial Period, Enteroendocrine Cells, Glucagon-Like Peptide 1
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