Vildagliptin, a Dipeptidyl Peptidase-IV Inhibitor, Improves Model-Assessed β-Cell Function in Patients with Type 2 Diabetes
Open accessAbstract
AIMS/HYPOTHESIS: The dipeptidyl peptidase IV inhibitor, vildagliptin, increases levels of intact glucagon-like peptide-1 (GLP-1) and improves glycemic control in patients with type 2 diabetes. Although GLP-1 is known to stimulate insulin secretion, vildagliptin does not affect plasma insulin levels in diabetic patients, suggesting that more sophisticated measures are necessary to ascertain the influence of vildagliptin on beta-cell function. METHODS: This study examined the effects of 28-d treatment with vildagliptin (100 mg, twice daily; n = 9) vs. placebo (n = 11) on beta-cell function in diabetic patients using a mathematical model that describes the insulin secretory rate as a function of glucose levels (beta-cell dose response), the change in glucose with time (derivative component), and a potentiation factor, which is a function of time and may reflect the actions of nonglucose secretagogues and other factors. RESULTS: Vildagliptin significantly increased the insulin secretory rate at 7 mmol/liter glucose (secretory tone), calculated from the dose response; the difference in least squares mean (deltaLSM) was 101 +/- 51 pmol.min(-1).m(-2) (P = 0.002). The slope of the beta-cell dose response, the derivative component, and the potentiation factor were not affected. Vildagliptin also significantly decreased mean prandial glucose (deltaLSM, -1.2 +/- 0.4 mmol/liter; P = 0.01) and glucagon (deltaLSM, -10.7 +/- 4.8 ng/liter; P = 0.03) levels and increased plasma levels of intact GLP-1 (deltaLSM, +10.8 +/- 1.6 pmol/liter; P < 0.0001) and gastric inhibitory polypeptide (deltaLSM, +43.4 +/- 9.4 pmol/liter; P < 0.0001) relative to placebo. CONCLUSION: Vildagliptin is an incretin degradation inhibitor that improves beta-cell function in diabetic patients by increasing the insulin secretory tone.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.
“Clinical studies of DPPIV inhibitors indicate that this class of drugs improves glycemic control in patients with type 2 diabetes mellitus.[35][36][37]”
From Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema (2008) · cites this paper as [37]
Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.
“Published trials have either not included subjects taking ACEi or have not commented on the inclusion of subjects exposed to ACEis.[35][36][37][38][39]”
From Dipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema (2008) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Glucagon-like peptide-1 7–36: a physiological incretin in man
Kreymann, B., Ghatei, M. A., Williams, G., & Bloom, S. R. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91194-9 · Cited by 1,928 · see citing works
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728 · see citing works
Nauck, M. A., Heimesaat, M. M., Orskov, C., Holst, J. J., Ebert, R., & Creutzfeldt, W. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116186 · Cited by 1,651 · see citing works
Self-citationZander, M., Madsbad, S., Madsen, J. L., & Holst, J. J. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07952-7 · Cited by 1,297 · see citing works
Self-citationDipeptidyl-peptidase IV (CD26)-role in the inactivation of regulatory peptides
Mentlein, R. (1999) · Regulatory Peptides · doi:10.1016/s0167-0115(99)00089-0 · Cited by 1,273 · see citing works
Cauter, E. V., Mestrez, F., Sturis, J., & Polonsky, K. (1992) · Diabetes · doi:10.2337/diab.41.3.368 · Cited by 938 · see citing works
A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test
Mari, A., Pacini, G., Murphy, E., Ludvik, B. H., & Nolan, J. J. (2001) · Diabetes Care · doi:10.2337/diacare.24.3.539 · Cited by 805 · see citing works
Self-citationScrocchi, L. A., Brown, T. J., Maclusky, N., Brubaker, P. L., Auerbach, A. B., Joyner, A. L., & Drucker, D. J. (1996) · Nature Medicine · doi:10.1038/nm1196-1254 · Cited by 793 · see citing works
Åhrén, B., Landin‐Olsson, M., Jansson, P., Svensson, M. K. E., Holmes, D., & Schweizer, A. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031907 · Cited by 710 · see citing works
Cauter, E. V., Mestrez, F., Sturis, J., et al. (1992) · Diabetes · doi:10.2337/diabetes.41.3.368 · Cited by 643 · see citing works
Villhauer, E. B., Brinkman, J. A., Naderi, G. B., Burkey, B. F., Dunning, B. E., Prasad, K., Mangold, B. L. K., Russell, M. E., & Hughes, T. E. (2003) · Journal of Medicinal Chemistry · doi:10.1021/jm030091l · Cited by 618 · see citing works
Self-citationThe Influence of GLP-1 on Glucose-Stimulated Insulin Secretion
Kjems, L. L., Holst, J. J., Vølund, A., & Madsbad, S. (2003) · Diabetes · doi:10.2337/diabetes.52.2.380 · Cited by 582 · see citing works
Self-citationGutzwiller, J., Drewe, J., Göke, B., Schmidt, H., Rohrer, B., Lareida, J., & Beglinger, C. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.276.5.r1541 · Cited by 521 · see citing works
T., V., T., K., S., M., & J., H. (2002) · Diabetologia · doi:10.1007/s00125-002-0878-6 · Cited by 518 · see citing works
Glucagon-like peptide-1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats
Farilla, L., Hui, H., Bertolotto, C., Kang, E., Bulotta, A., Di Mario, U., & Perfetti, R. (2002) · Endocrinology · doi:10.1210/en.2002-220405 · Cited by 502 · see citing works
Inhibition of the activity of dipeptidyl-peptidase IV as a treatment for type 2 diabetes.
Holst, J. J., & Deacon, C. F. (1998) · Diabetes · doi:10.2337/diabetes.47.11.1663 · Cited by 487 · see citing works
Self-citationRole of fatty acids in the pathogenesis of insulin resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diabetes.46.1.3 · Cited by 479 · see citing works
Miyawaki, K., Yamada, Y., Yano, H., Niwa, H., Ban, N., Ihara, Y., Kubota, A., Fujimoto, S., Kajikawa, M., Kuroe, A., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.14843 · Cited by 454 · see citing works
Deacon, C. F., Nauck, M. A., Meier, J. J., Hücking, K., & Holst, J. J. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.10.6855 · Cited by 439 · see citing works
Self-citationAhrén, B., Simonsson, E., Larsson, H., Landin-Olsson, M., Torgeirsson, H., Jansson, P.-A., Sandqvist, M., Båvenholm, P., Efendic, S., Eriksson, J. W., et al. (2002) · Diabetes Care · doi:10.2337/diacare.25.5.869 · Cited by 421 · see citing works
Glucagon-like peptide-1 prevents beta cell glucolipotoxicity
Joly, E. C., Prentki, M., Buteau, J., El-Assaad, W., Rhodes, C. J., & Rosenberg, L. (2004) · Diabetologia · doi:10.1007/s00125-004-1379-6 · Cited by 337 · see citing works
Creutzfeldt, W., Kleine, N., Willms, B., Ørskov, C., Holst, J. J., & Nauck, M. A. (1996) · Diabetes Care · doi:10.2337/diacare.19.6.580 · Cited by 328 · see citing works
Self-citationMeier, J. J., Gallwitz, B., Siepmann, N., Holst, J. J., Deacon, C. F., Schmidt, W. E., & Nauck, M. A. (2003) · Diabetologia · doi:10.1007/s00125-003-1103-y · Cited by 314 · see citing works
Self-citationHansotia, T., Baggio, L. L., Delmeire, D., Hinke, S. A., Yamada, Y., Tsukiyama, K., Seino, Y., Holst, J. J., Schuit, F., & Drucker, D. J. (2004) · Diabetes · doi:10.2337/diabetes.53.5.1326 · Cited by 309 · see citing works
Self-citationMeal and oral glucose tests for assessment of β-cell function: modeling analysis in normal subjects
Mari, A., Schmitz, O., Gastaldelli, A., Oestergaard, T., Nyholm, B., & Ferrannini, E. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00093.2002 · Cited by 303 · see citing works
Self-citationGLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans
Näslund, E. B., Bogefors, J., Skogar, S., Grybäck, P., Jacobsson, H., Holst, J. J., & Hellström, P. M. (1999) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1999.277.3.r910 · Cited by 286 · see citing works
Self-citationAssessing Insulin Secretion by Modeling in Multiple-Meal Tests
Mari, A., Tura, A., Gastaldelli, A., & Ferrannini, E. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s221 · Cited by 248 · see citing works
Self-citationBalkan, B., Kwasnik, L., Miserendino, R., Holst, J. J., & Li, X. (1999) · Diabetologia · doi:10.1007/s001250051445 · Cited by 211 · see citing works
Self-citationRitzel, R. A., �rskov, C., Holst, J. J., & Nauck, M. A. (1995) · Diabetologia · doi:10.1007/bf00401846 · Cited by 210 · see citing works
Self-citationPrigeon, R. L., Quddusi, S., Paty, B., & D'Alessio, D. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00024.2003 · Cited by 199 · see citing works
Deacon, C. F., Åhrén, B., & Holst, J. J. (2004) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.13.9.1091 · Cited by 194 · see citing works
Self-citationImproved glucose tolerance and insulin secretion by inhibition of dipeptidyl peptidase IV in mice
Åhrén, B., Holst, J. J., Mårtensson, H., & Balkan, B. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00600-2 · Cited by 193 · see citing works
Self-citationDeacon, C. F., Wamberg, S., Bie, P., Hughes, T., & Holst, J. J. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.1720355 · Cited by 146 · see citing works
Self-citationÅhrén, B., Larsson, H., & Holst, J. J. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.2.3728 · Cited by 135 · see citing works
Self-citationD’Alessio, D. A., Prigeon, R. L., & Ensinck, J. W. (1995) · Diabetes · doi:10.2337/diab.44.12.1433 · Cited by 120 · see citing works
Glucagon-Like Peptide-1 Augments Insulin-Mediated Glucose Uptake in the Obese State
Egan, J. M., Meneilly, G. S., Habener, J. F., & Elahi, D. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.8.8743 · Cited by 119 · see citing works
Lambeir, A., Durinx, C., Proost, P., Damme, J. V., Scharpé, S., & Meester, I. D. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02982-9 · Cited by 112 · see citing works
Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects
Boden, G., Ruiz, J. P. G., Kim, C. J., & Chen, X. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.2.e251 · Cited by 75 · see citing works
Characterization of GLP-1 Effects on β-Cell Function After Meal Ingestion in Humans
Ahrén, B., Holst, J. J., & Mari, A. (2003) · Diabetes Care · doi:10.2337/diacare.26.10.2860 · Cited by 72 · see citing works
Self-citationMeneilly, G. S., McIntosh, C. H. S., Pederson, R. A., Habener, J. F., Gingerich, R. L., Egan, J. M., Finegood, D. T., & Elahi, D. (2001) · Diabetes Care · doi:10.2337/diacare.24.11.1951 · Cited by 63 · see citing works
Mitani, H., Takimoto, M., & Kimura, M. (2002) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.88.451 · Cited by 28 · see citing works
Ritzel, R. A., �rskov, C., Holst, J. J., et al. (1995) · Diabetologia · doi:10.1007/s001250050344 · Cited by 22 · see citing works
Self-citationLarsen, M. O., Rolin, B. C., Ribel, U., Wilken, M., Deacon, C. F., Svendsen, O., Gotfredsen, C. F., & Carr, R. D. (2003) · Journal of Diabetes Research · doi:10.1155/edr.2003.93 · Cited by 16 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Physiology of Glucagon-like Peptide 1
Holst, J. J. (2007) · Physiological Reviews · doi:10.1152/physrev.00034.2006 · Cited by 3,371 · see citing works
Self-citationRaz, I., Hanefeld, M., Xu, L., Caria, C., Williams-Herman, D., Khatami, H., & Sitagliptin Study 023 Group (2006) · Diabetologia · doi:10.1007/s00125-006-0416-z · Cited by 614 · see citing works
Nauck, M. (2016) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12591 · Cited by 429 · see citing works
Dunning, B. E., & Gerich, J. E. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0026 · Cited by 369 · see citing works
Self-citationMatikainen, N., Mänttäri, S., Schweizer, A., Ulvestad, A., Mills, D., Dunning, B. E., Foley, J. E., & Taskinen, M.-R. (2006) · Diabetologia · doi:10.1007/s00125-006-0340-2 · Cited by 336 · see citing works
Self-citationEfficacy and tolerability of vildagliptin monotherapy in drug-naïve patients with type 2 diabetes
Pi-Sunyer, F. X., Schweizer, A., Mills, D., & Dejager, S. (2007) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2006.12.009 · Cited by 312 · see citing works
Rosenstock, J., Kim, S. W., Baron, M. A., Camisasca, R. ‐., Cressier, F., Couturier, A., & Dejager, S. (2007) · Diabetes, Obesity and Metabolism · doi:10.1111/j.1463-1326.2006.00698.x · Cited by 255 · see citing works
Madsen, K., Knudsen, L. B., Agersoe, H., Nielsen, P. F., Thøgersen, H., Wilken, M., & Johansen, N. L. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070861j · Cited by 244 · see citing works
Glucagon-like peptide-1: From extract to agent. The Claude Bernard Lecture, 2005
Holst, J. J. (2006) · Diabetologia · doi:10.1007/s00125-005-0107-1 · Cited by 228 · see citing works
Self-citationRosenstock, J., Foley, J. E., Rendell, M., Landin-Olsson, M., Holst, J. J., Deacon, C. F., Rochotte, E., & Baron, M. A. (2008) · Diabetes Care · doi:10.2337/dc07-1616 · Cited by 153 · see citing works
Self-citationDipeptidyl Peptidase IV in Angiotensin-Converting Enzyme Inhibitor–Associated Angioedema
Byrd, J. B., Touzin, K., Sile, S., Gainer, J. V., Yu, C., Nadeau, J., Adam, A., & Brown, N. J. (2008) · Hypertension · doi:10.1161/hypertensionaha.107.096552 · Cited by 147 · see citing works
Effects of GLP-1 and Incretin-Based Therapies on Gastrointestinal Motor Function
Marathe, C. S., Rayner, C. K., Jones, K. L., & Horowitz, M. (2011) · Experimental Diabetes Research · doi:10.1155/2011/279530 · Cited by 138 · see citing works
D'Alessio, D. A., Denney, A. M., Hermiller, L. M., Prigeon, R. L., Martin, J. M., Tharp, W. G., Saylan, M. L., He, Y., Dunning, B. E., Foley, J. E., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1135 · Cited by 99 · see citing works
Self-citationEleftheriadou, I., Grigoropoulou, P., Katsilambros, N., & Tentolouris, N. (2008) · Current Diabetes Reviews · doi:10.2174/157339908786241133 · Cited by 55 · see citing works
Huang, J.-H., Chen, Y.-C., Lee, T.-I., Kao, Y.-H., Chazo, T.-F., Chen, S.-A., & Chen, Y.-J. (2016) · Peptides · doi:10.1016/j.peptides.2016.02.007 · Cited by 36 · see citing works
GLP-1-Based Strategies: A Physiological Analysis of Differential Mode of Action
Burcelin, R., Gourdy, P., & Dalle, S. (2014) · Physiology · doi:10.1152/physiol.00009.2013 · Cited by 26 · see citing works
- Authors
- Mari, A., Sallas, W. M., He, Y. L., Watson, C., Ligueros-Saylan, M., Dunning, B. E., Deacon, C. F., Holst, J. J., & Foley, J. E.
- Affiliations
- National Research Council (IT)
- Novartis (United States) (US)
- University of Copenhagen (DK)
- Corresponding author
- Mari, A.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2005-08
- Volume
- 90
- Issue
- 8
- Pages
- 4888-4894
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2043121816
- Cited by
- 361
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 13 · 2014: 28 · 2013: 17 · 2012: 18
- FWCI
- 29.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (other-oa)
- 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
- vildagliptin, DPP-4 inhibitors, type 2 diabetes, beta-cell function, insulin secretion, glucagon-like peptide-1, incretin-based therapy, glucagon, glucose-dependent insulinotropic polypeptide
- MeSH terms
- Vildagliptin, Insulin Secretion, Adamantane, Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Enzyme Inhibitors, Female, Glycoproteins, Humans, Insulin, Islets of Langerhans, Male, Middle Aged, Models, Biological, Nitriles, Pyrrolidines, Treatment Outcome, Dipeptidyl Peptidase 4, Adenosine Deaminase Inhibitors
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
