Exenatide Versus Glibenclamide in Patients with Diabetes
Abstract
BACKGROUND: Incretin-based therapies have provided additional options for the treatment of type 2 diabetes mellitus. The aim of our study was to evaluate the effects of exenatide compared to glibenclamide on body weight, glycemic control, beta-cell function, insulin resistance, and inflammatory state in patients with diabetes. METHODS: One hundred twenty-eight patients with uncontrolled type 2 diabetes mellitus receiving therapy with metformin were randomized to take exenatide 5 microg twice a day or glibenclamide 2.5 mg three times a day and titrated to exenatide 10 microg twice a day or glibenclamide 5 mg three times a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance (HOMA-IR) index, homeostasis model assessment beta-cell function (HOMA-beta) index, plasma proinsulin (PPr), PPr/FPI ratio, resistin, retinol binding protein-4 (RBP-4), and high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3, 6, 9, and 12 months. RESULTS: Body weight and BMI decreased with exenatide and increased with glibenclamide. A similar improvement of HbA(1c), FPG, and PPG was obtained in both groups, whereas FPI decreased with exenatide and increased with glibenclamide. The HOMA-IR index decreased and the HOMA-beta index increased with exenatide but not with glibenclamide. A decrease of PPr was reported in both groups, but only glibenclamide decreased the PPr/FPI ratio. Resistin and RBP-4 decreased with exenatide and increased with glibenclamide. A decrease of Hs-CRP was obtained with exenatide, whereas no variations were observed with glibenclamide. CONCLUSIONS: Both exenatide and glibenclamide gave a similar improvement of glycemic control, but only exenatide gave improvements of insulin resistance and beta-cell function, giving also a decrease of body weight and of inflammatory state.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Individual randomized controlled trial findings on the effects of GLP-1 receptor agonists on inflammatory biomarkers are inconsistent.
“The findings, however, have been inconsistent. Some studies report significant reductions in TNF-α and CRP with GLP-1 RA therapy compared to placebo or other antidiabetic medications (6, 15, 17, 18), while others show non-significant or conflicting results (19, 20).”
Exenatide showed better anti-inflammatory activity than metformin (SMD = -0.95; 95% CI: -1.78 to -0.13) in spite of metformin's proven pleiotropic advantages.
“This is clear when compared to metformin (SMD = -0.95; 95% CI: -1.78 to -0.13), where exenatide showed better anti-inflammatory activity in spite of metformin’s proven pleiotropic advantages (13, 19, 38).”
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Use and Abuse of HOMA Modeling
Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1487 · Cited by 5,114 · see citing works
Buse, J. B., Henry, R. R., Han, J., Kim, D. D., Fineman, M. S., Baron, A. D., & for the Exenatide-113 Clinical Study Group (2004) · Diabetes Care · doi:10.2337/diacare.27.11.2628 · Cited by 1,346 · see citing works
Kendall, D. M., Riddle, M. C., Rosenstock, J., Zhuang, D., Kim, D. D., Fineman, M. S., & Baron, A. D. (2005) · Diabetes Care · doi:10.2337/diacare.28.5.1083 · Cited by 1,177 · see citing works
Heine, R. J., Van Gaal, L. F., Johns, D., Mihm, M. J., Widel, M. H., Brodows, R. G., & for the GWAA Study Group* (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-143-8-200510180-00006 · Cited by 795 · see citing works
Deacon, C. F., Johnsen, A. H., & Holst, J. J. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.3.7883856 · Cited by 792 · see citing works
Bunck, M. C., Diamant, M., Cornér, A., Eliasson, B., Malloy, J. L., Shaginian, R. M., Deng, W., Kendall, D. M., Taskinen, M.-R., Smith, U., et al. (2009) · Diabetes Care · doi:10.2337/dc08-1797 · Cited by 388 · see citing works
Moretto, T. J., Milton, D. R., Ridge, T. D., MacConell, L. A., Okerson, T., Wolka, A. M., & Brodows, R. G. (2008) · Clinical Therapeutics · doi:10.1016/j.clinthera.2008.08.006 · Cited by 350 · see citing works
Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006
Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., Franch, H. A., Franklin, B., Kris-Etherton, P., Harris, W. S., Howard, B., et al. (2006) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.0000238352.25222.5e · Cited by 345 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vilsboll, T., Christensen, M., Junker, A. E., Knop, F. K., & Gluud, L. L. (2012) · BMJ · doi:10.1136/bmj.d7771 · Cited by 970 · see citing works
GLP-1 and the kidney: from physiology to pharmacology and outcomes in diabetes
Muskiet, M. H. A., Tonneijck, L., Smits, M. M., van Baar, M. J. B., Kramer, M. H. H., Hoorn, E. J., Joles, J. A., & van Raalte, D. H. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.123 · Cited by 407 · see citing works
Robinson, L. E., Holt, T. A., Rees, K., Randeva, H. S., & O'Hare, J. P. (2013) · BMJ Open · doi:10.1136/bmjopen-2012-001986 · Cited by 296 · see citing works
Exenatide Exerts a Potent Antiinflammatory Effect
Chaudhuri, A., Ghanim, H., Vora, M., Sia, C. L., Korzeniewski, K., Dhindsa, S., Makdissi, A., & Dandona, P. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1508 · Cited by 284 · see citing works
Bray, J. J. H., Foster‐Davies, H., Salem, A., Hoole, A. L., Obaid, D. R., Halcox, J. P. J., & Stephens, J. W. (2021) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14399 · Cited by 194 · see citing works
“They comprised 6749 patients (inflammation evaluated in 6560, oxidative stress in 701 patients), included a median (IQR) study population of 60 (33-122) participants, and had a median (IQR) follow-up of 6 months (84-182 days).”
BackgroundDeacon, C. F., Mannucci, E., & Ahrén, B. (2012) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2012.01603.x · Cited by 190 · see citing works
Potts, J. E., Gray, L. J., Brady, E. M., Khunti, K., Davies, M. J., & Bodicoat, D. H. (2015) · PLOS ONE · doi:10.1371/journal.pone.0126769 · Cited by 163 · see citing works
Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research
Levin, P. A., Nguyen, H., Wittbrodt, E., & Kim, S. C. (2017) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s130834 · Cited by 107 · see citing works
Incretin Effects on β-Cell Function, Replication, and Mass
Garber, A. J. (2011) · Diabetes Care · doi:10.2337/dc11-s230 · Cited by 92 · see citing works
Derosa, G., Franzetti, I. G., Querci, F., Carbone, A., Ciccarelli, L., Piccinni, M. N., Fogari, E., & Maffioli, P. (2012) · Diabetic Medicine · doi:10.1111/j.1464-5491.2012.03699.x · Cited by 70 · see citing works
Self-citationRen, Y., Chen, Y., Zheng, W., Kong, W., Liao, Y., Zhang, J., Wang, M., & Zeng, T. (2025) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.16366 · Cited by 59 · see citing works
Cardiovascular Effects of Glucagon-Like Peptide-1 Receptor Agonists
Kang, Y. M., & Jung, C. H. (2016) · Endocrinology and Metabolism · doi:10.3803/enm.2016.31.2.258 · Cited by 51 · see citing works
Clinical use of liraglutide in type 2 diabetes and its effects on cardiovascular risk factors
Varanasi, A., Patel, P., Makdissi, A., Dhindsa, S., Chaudhuri, A., & Dandona, P. (2012) · Endocrine Practice · doi:10.4158/ep11169.or · Cited by 50 · see citing works
Treatment potential of the GLP-1 receptor agonists in type 2 diabetes mellitus: a review
Østergaard, L., Frandsen, C. S., & Madsbad, S. (2016) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.2016.1121808 · Cited by 38 · see citing works
Zhao, F., Wang, H., Li, S., Yun, H., & Su, W. (2026) · PeerJ · doi:10.7717/peerj.20710 · Cited by 6 · see citing works
Kanbay, M., Shah, E., AlShiab, R., Ozbek, L., Ay, S., Rustamov, A., Covic, A., Mallamaci, F., & Zoccali, C. (2026) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.71106 · Cited by 4 · see citing works
Alrasheed, T., Mostafa, M. E. A., Madkhali, M. A., & Khairy, H. A. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1734549 · Cited by 4 · see citing works
- Authors
- Derosa, G., Maffioli, P., Salvadeo, S. A. T., Ferrari, I., Ragonesi, P. D., Querci, F., Franzetti, I. G., Gadaleta, G., Ciccarelli, L., Piccinni, M. N., D'Angelo, A., & Cicero, A. F. G.
- Affiliations
- University of Pavia (IT)
- Diabetes Care Unit, S. Carlo Hospital, Milano, Italy.
- Ospedale Pesenti Fenaroli (IT)
- Metabolic Unit, Regional Hospital, Varese, Italy.
- Division of Medicine, Civic Hospital, Cittiglio, Varese, Italy.
- RSA Don Leone Porta, Milano, Italy.
- Istituti Ospitalieri di Cremona (IT)
- Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
- University of Bologna (IT)
- Corresponding author
- Derosa, G.
- Venue
- Diabetes Technology & Therapeutics
- Publisher
- SAGE Publications
- Published
- 2010-03
- Volume
- 12
- Issue
- 3
- Pages
- 233-240
- ISSN
- 1520-9156 (ISSN-L)
- 1557-8593
- OpenAlex
- W2061691264
- Cited by
- 125
- References
- 9
- Citations by year
- 2026: 5 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 5 · 2017: 8 · 2016: 6 · 2015: 13 · 2014: 8 · 2013: 16 · 2012: 18
- FWCI
- 14.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Technology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- exenatide, glibenclamide, type 2 diabetes, glycemic control, insulin resistance, beta-cell function, body weight, inflammation, proinsulin, resistin, retinol-binding protein 4, C-reactive protein, metformin, incretin-based therapy, sulfonylureas
- MeSH terms
- Exenatide, Adolescent, Adult, Aged, Aged, 80 and over, Blood Glucose, Body Weight, C-Reactive Protein, Diabetes Mellitus, Type 2, Female, Glyburide, Glycated Hemoglobin, Humans, Hyperglycemia, Hypoglycemic Agents, Insulin Resistance, Male, Metformin, Middle Aged, Peptides, Proinsulin, Venoms, Body Mass Index, Insulin-Secreting Cells, Resistin, Incretins, Retinol-Binding Proteins, Plasma, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
