Addition of a dipeptidyl peptidase-4 inhibitor, sitagliptin, to ongoing therapy with the glucagon-like peptide-1 receptor agonist liraglutide: a randomized controlled trial in patients with type 2 diabetes
Abstract
Aim To determine whether the addition of sitagliptin to pre-existing therapy with liraglutide changes glycaemic excursions after a mixed meal. Methods A total of 16 patients with type 2 diabetes treated with metformin and liraglutide (1.2 mg/d for ≥2 weeks) were randomized (sealed envelopes), within a cross-over design, to be studied on two occasions, after an overnight fast, with (1) sitagliptin (100 mg orally) and (2) placebo (patients and care givers blinded) administered 60 minutes before a mixed meal, or vice versa. Glucose excursions (incremental area under the curve [AUC]; primary endpoint) and insulin, C-peptide, glucagon and incretin concentrations were measured. The study setting was a metabolic study unit at a specialized diabetes hospital. Results All 16 patients completed the study and were analysed. Glucose (AUC glucose 319 ± 30 [placebo] vs 315 ± 18 mmol.L -1 .min -1 [sitagliptin], Δ 7 [95% confidence interval -50 to 63] mmol.L -1 .min -1 ), insulin, C-peptide and glucagon concentrations were not affected significantly by sitagliptin treatment ( P = .60-1.00). Intact glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) concentrations were augmented by sitagliptin, by 78.4% and 90.2%, respectively (both P Conclusions Sitagliptin, in patients already treated with a GLP-1 receptor agonist (liraglutide), increased intact GLP-1 and GIP concentrations, but with marginal, non-significant effects on glycaemic control. GLP-1 receptors h…
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There is no added glucose-lowering benefit of using GLP-1 RAs (or dual GIP and GLP-1 RA) together with a DPP-4 inhibitor beyond that of the GLP-1 RA alone.
“We do not recommend using GLP-1 RAs (or the dual GIP and GLP-1 RA) together with a DPP-4 inhibitor as there is no added glucose-lowering benefit beyond that of the GLP-1 RA alone (119-121).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [121]
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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-citationGLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus
Meier, J. J. (2012) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2012.140 · Cited by 1,311 · see citing works
Pyke, C., Heller, R. S., Kirk, R. K., Ørskov, C., Reedtz-Runge, S., Kaastrup, P., Hvelplund, A., Bardram, L., Calatayud, D., & Knudsen, L. B. (2014) · Endocrinology · doi:10.1210/en.2013-1934 · Cited by 876 · cited 4× · see citing works
“quential improvements in glucose control can only partially be inhibited by the GLP-1 receptor agonist exendin [9-39].”
BackgroundMethodInfluentialAgersø, H., Jensen, L. B., Elbrønd, B., Rolan, P., & Zdravkovic, M. (2002) · Diabetologia · doi:10.1007/s00125-001-0719-z · Cited by 510 · see citing works
Edwards, C. M., Todd, J. F., Mahmoudi, M., Wang, Z., Wang, R. M., Ghatei, M. A., & Bloom, S. R. (1999) · Diabetes · doi:10.2337/diabetes.48.1.86 · Cited by 344 · see citing works
Elbrønd, B., Jakobsen, G., Larsen, S., Agersø, H., Jensen, L. B., Rolan, P., Sturis, J., Hatorp, V., & Zdravkovic, M. (2002) · Diabetes Care · doi:10.2337/diacare.25.8.1398 · Cited by 279 · see citing works
Rosenstock, J., Raccah, D., Korányi, L., Maffei, L., Boka, G., Miossec, P., & Gerich, J. E. (2013) · Diabetes Care · doi:10.2337/dc12-2709 · Cited by 253 · see citing works
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Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868 · see citing works
Self-citation9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
Gilbert, M. P., & Pratley, R. E. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00178 · Cited by 407 · see citing works
Miras, A. D., Pérez-Pevida, B., Aldhwayan, M., Kamocka, A., McGlone, E. R., Al-Najim, W., Chahal, H., Batterham, R. L., McGowan, B., Khan, O., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30157-3 · Cited by 190 · see citing works
The Role of Glucagon in the Pathophysiology and Treatment of Type 2 Diabetes
Hædersdal, S., Lund, A., Knop, F. K., & Vilsbøll, T. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2017.12.003 · Cited by 162 · see citing works
Ndumele, C. E., Rodriguez, F., Dixon, D. L., Khan, S. S., Mukherjee, D., Bajaj, M., Bangalore, S., Bozkurt, B., Breathett, K., Clarke, S. L., et al. (2026) · JACC · doi:10.1016/j.jacc.2026.03.056 · Cited by 90 · see citing works
Lajthia, E., Bucheit, J. D., Nadpara, P. A., Dixon, D. L., Caldas, L. M., Murchie, M., & Sisson, E. M. (2019) · Pharmacy Practice · doi:10.18549/pharmpract.2019.4.1588 · Cited by 25 · see citing works
- Authors
- Nauck, M. A., Kahle, M., Baranov, O., Deacon, C. F., & Holst, J. J.
- Affiliations
- Diabeteszentrum Bad Lauterberg (DE)
- University of Copenhagen (DK)
- Corresponding author
- Nauck, Michael A.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2016-11-09
- Volume
- 19
- Issue
- 2
- Pages
- 200-207
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2528223296
- Cited by
- 44
- References
- 7
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 6 · 2019: 7 · 2018: 4 · 2017: 6
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Merck Research Laboratories, Rahway, New Jersey
- NovoNordisk Foundation
- 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 › Natural Antidiabetic Agents Studies
- Keywords
- sitagliptin, liraglutide, type 2 diabetes, DPP-4 inhibitors, GLP-1 receptor agonists, combination therapy, incretins, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, insulin, C-peptide, glucagon, metformin
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Sitagliptin Phosphate, Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Adult, Aged, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Female, Gastric Inhibitory Polypeptide, Glucagon, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Metformin, Middle Aged, Treatment Outcome, Cross-Over Studies, Glucagon-Like Peptide 1, Dipeptidyl-Peptidase IV Inhibitors
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