Liraglutide enhances insulin secretion and prolongs the remission period in adults with newly diagnosed type 1 diabetes (the NewLira study): A randomized, double‐blind, placebo‐controlled trial
Open accessAbstract
Aim: To test the effect of the glucagon‐like peptide‐1 receptor agonist, liraglutide, on residual beta‐cell function in adults with newly diagnosed type 1 diabetes. Materials and Methods: In a multicentre, double‐blind, parallel‐group trial, adults with newly diagnosed type 1 diabetes and stimulated C‐peptide of more than 0.2 nmol/L were randomized (1:1) to 1.8‐mg liraglutide (Victoza) or placebo once daily for 52 weeks with 6 weeks of follow‐up with only insulin treatment. The primary endpoint was the between‐group difference in C‐peptide area under the curve (AUC) following a liquid mixed‐meal test after 52 weeks of treatment. Results: Sixty‐eight individuals were randomized. After 52 weeks, the 4‐hour AUC C‐peptide response was maintained with liraglutide, but decreased with placebo ( P = .002). Six weeks after end‐of‐treatment, C‐peptide AUCs were similar for liraglutide and placebo. The average required total daily insulin dose decreased from 0.30 to 0.23 units/kg/day with liraglutide, but increased from 0.29 to 0.43 units/kg/day in the placebo group at week 52 ( P < .001). Time without the need for insulin treatment was observed in 13 versus two patients and lasted for 22 weeks (from 3 to 52 weeks) versus 6 weeks (from 4 to 8 weeks) on average for liraglutide and placebo, respectively. Patients treated with liraglutide had fewer episodes of hypoglycaemia compared with placebo‐treated patients. The adverse events with liraglutide were predominantly gastrointestinal and transient. Conclusions: Treatment with liraglutide improves residual beta‐cell function and reduces the dose of insulin during the first year after diagnosis. Beta‐cell function was similar at 6 weeks postliraglutide treatment.
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?
Liraglutide improved residual β-cell function and reduced insulin requirements in people with adult-onset type 1 diabetes during the first year post-diagnosis.
“Similarly, liraglutide improved residual βcell function and reduced insulin requirements in people with adultonset type 1 diabetes during the first year postdiagnosis.50”
From The future of type 1 diabetes therapy (2025) · cites this paper as [50]
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
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-citationJakobsen, J. C., Gluud, C., Wetterslev, J., & Winkel, P. (2017) · BMC Medical Research Methodology · doi:10.1186/s12874-017-0442-1 · Cited by 2,747 · cited 1× · see citing works
“24 To account for the influence of missingness, for outcomes collected at multiple visits, a mixed-effects linear regression model was used, where the outcome of interest at all visits was included as an outcome, and allocation and week were included as fixed effects, while participants were…”
Steffes, M. W., Sibley, S., Jackson, M., & Thomas, W. (2003) · Diabetes Care · doi:10.2337/diacare.26.3.832 · Cited by 695 · see citing works
Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus.
Killestein, J. (2002) · New England Journal of Medicine · doi:10.1056/nejm200210033471416 · Cited by 694 · see citing works
6. Glycemic Targets: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s006 · Cited by 684 · see citing works
Digon, B., & Rother, K. I. (2003) · Diabetes Care · doi:10.1089/152091503765692036 · Cited by 638 · cited 1×
“3,4 15 Hence, treatment with GLP-1 receptor agonists (GLP-1RAs) might have beneficial effects in people with type 1 diabetes with residual beta-cell function.”
International Hypoglycaemia Study Group (2017) · Diabetes Care · doi:10.2337/dc16-2215 · Cited by 608 · see citing works
GAD treatment and insulin secretion in recent-onset type 1 diabetes
Ludvigsson, J., Faresjö, M., Hjorth, M., Axelsson, S., Chéramy, M., Pihl, M., Vaarala, O., Forsander, G., Ivarsson, S., Johansson, C., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804328 · Cited by 520 · see citing works
Palmer, J. P., Fleming, G. A., Greenbaum, C. J., Herold, K. C., Jansa, L. D., Kolb, H., Lachin, J. M., Polonsky, K. S., Pozzilli, P., Skyler, J. S., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.1.250 · Cited by 491 · see citing works
Moran, A., Bundy, B. N., BECKER, D. J., DiMeglio, L. A., Gitelman, S. E., Goland, R., Greenbaum, C. J., Herold, K. C., Marks, J. B., Raskin, P., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60023-9 · Cited by 356 · see citing works
Mathieu, C., Zinman, B., Hemmingsson, J. U., Woo, V., Colman, P., Christiansen, E., Linder, M., Bode, B., & for the ADJUNCT ONE Investigators (2016) · Diabetes Care · doi:10.2337/dc16-0691 · Cited by 347 · 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
Ahrén, B., Hirsch, I. B., Pieber, T. R., Mathieu, C., Gómez-Peralta, F., Hansen, T. K., Philotheou, A., Birch, S., Christiansen, E., Jensen, T. J., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0690 · Cited by 262 · cited 1× · see citing works
“31 In another trial, adults with type 1 diabetes and a mean time from diagnosis of approximately 11 weeks were randomized to treatment with an IL-21 antibody, liraglutide, IL-21 antibody + liraglutide or placebo, as an adjunct to insulin therapy.”
Sherry, N. A., Chen, W., Kushner, J. A., Glandt, M., Tang, Q., Tsai, S., Santamaria, P., Bluestone, J. A., Brillantes, A.-M. B., & Herold, K. C. (2007) · Endocrinology · doi:10.1210/en.2007-0358 · Cited by 169 · see citing works
ISEC: a program to calculate insulin secretion.
Hovorka, R., Soons, P., & Young, M. A. (1996) · Computer Methods and Programs in Biomedicine · doi:10.1016/0169-2607(96)01755-5 · Cited by 169 · see citing works
GLP-1 receptor signaling: effects on pancreatic beta-cell proliferation and survival.
Buteau, J. (2008) · Diabetes & Metabolism · doi:10.1016/s1262-3636(08)73398-6 · Cited by 152 · see citing works
Rother, K. I., Spain, L. M., Wesley, R. A., Digon, B. J., Baron, A., Chen, K., Nelson, P., Dosch, H.-M., Palmer, J. P., Brooks-Worrell, B., et al. (2009) · Diabetes Care · doi:10.2337/dc09-0773 · Cited by 133 · cited 1× · see citing works
“25,26 30 In all studies, placebo-corrected reductions of body weight from 4.3 to 6.8 kg, and in total daily insulin dose of between 5 and 10 U/day, have been found for liraglutide 1.8-mg OD.”
InfluentialUtzschneider, K., Prigeon, R., Tong, J., Gerchman, F., Carr, D. B., Zraika, S., Udayasankar, J., Montgomery, B., Mari, A., & Kahn, S. E. (2007) · Diabetologia · doi:10.1007/s00125-007-0819-5 · Cited by 116 · see citing works
Madsbad, S. (1983) · Diabetologia · doi:10.1007/bf00250151 · Cited by 107 · cited 1× · see citing works
“Type 1 diabetes is very heterogeneous in relation to disease progression, 2 but the current study is too small to identify subgroups that could benefit more from treatment with GLP-1RAs.”
Self-citationFrandsen, C. S., Dejgaard, T. F., Holst, J. J., Andersen, H. U., Thorsteinsson, B., & Madsbad, S. (2015) · Diabetes Care · doi:10.2337/dc15-1037 · Cited by 103 · see citing works
Self-citationZhang, J., Tokui, Y., Yamagata, K., Kozawa, J., Sayama, K., Iwahashi, H., Okita, K., Miuchi, M., Konya, H., Hamaguchi, T., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0737-6 · Cited by 79 · see citing works
Prevention and Reversal of Type 1 Diabetes—Past Challenges and Future Opportunities
Skyler, J. (2015) · Diabetes Care · doi:10.2337/dc15-0349 · Cited by 78 · see citing works
Park, J., Ntelis, S., Yunasan, E., Downton, K. D., Yip, T. C.-F., Munir, K. M., & Haq, N. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad471 · Cited by 69 · see citing works
Dejgaard, T., Schmidt, S., Frandsen, C., Vistisen, D., Madsbad, S., Andersen, H. U., & Nørgaard, K. (2019) · Diabetes, obesity and metabolism · doi:10.1111/dom.13911 · Cited by 69 · see citing works
Self-citationMethods and Guidelines for Measurement of Glucagon in Plasma
Holst, J. J., & Albrechtsen, N. J. W. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20215416 · Cited by 59 · see citing works
Self-citationDisease-Modifying Therapies in Type 1 Diabetes: A Look into the Future of Diabetes Practice
Greenbaum, C. J., VanBuecken, D., & Lord, S. M. (2019) · Drugs · doi:10.1007/s40265-018-1035-y · Cited by 55 · see citing works
Johansen, N., Dejgaard, T., Lund, A., Schlüntz, C., Frandsen, C., Forman, J., Albrechtsen, N. J. W., Holst, J., Pedersen-Bjergaard, U., Madsbad, S., et al. (2020) · The Lancet Diabetes and Endocrinology · doi:10.1016/s2213-8587(20)30030-9 · Cited by 53 · cited 2× · see citing works
“25,27 – 30 Importantly, a prespecified subgroup analysis from the ADJUNCT TWO trial with 1.8-mg liraglutide indicated that in those with residual beta-cell function ( n = 183, C-peptide > 0.03 nmol/L), HbA1c showed a placebo-corrected reduction of 8.4 mmol/mol.”
InfluentialSelf-citationMadsbad, S., Krarup, T., Regeur, L., Faber, O. K., & Binder, C. (1980) · Acta Endocrinologica · doi:10.1530/acta.0.0950359 · Cited by 52 · see citing works
Self-citationKielgast, U., Asmar, M., Madsbad, S., & Holst, J. (2010) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2009-2440 · Cited by 51 · cited 1× · see citing works
“16 In clinical trials investigating GLP-1RAs as an add-on to insulin in long-standing type 1 diabetes, an average reduction of 3 mmol/mol in HbA1c, 8 units of insulin per day and 5 kg in body weight, with no elevated risk of hypoglycaemia or ketoacidosis, was found.”
Self-citationRondas, D., Bugliani, M., D’Hertog, W., Lage, K., Masini, M., Waelkens, E., Marchetti, P., Mathieu, C., & Overbergh, L. (2013) · Journal of Proteome Research · doi:10.1021/pr400527q · Cited by 32 · cited 1× · see citing works
“3,4 15 Hence, treatment with GLP-1 receptor agonists (GLP-1RAs) might have beneficial effects in people with type 1 diabetes with residual beta-cell function.”
Flagged first, then by citations
1 of the 31 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes control and complications trial research group. Ann Intern Med. 1998;128(7):517-523. doi:10. 7326/0003-4819-128-7-199804010-00001 · DOI · Paper page
- Dejgaard TF, Frandsen CS, Hansen TS, et al. Efficacy and safety of lir- aglutide for overweight adult patients with type 1 diabetes and insuf- ficient glycaemic control (Lira-1): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2016;4(3):221- 232. doi:10.1016/S2213-8587(15)00436-2 · DOI
- von Herrath M, Bain SC, Bode B, et al. Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo- controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2021;9(4):212- 224. doi:10.1016/S2213-8587(21)00019-X · DOI · Paper page
Cited by
Sorted by citations
Oprea, A. D., Ostapenko, L. J., Sweitzer, B., Selzer, A., Irizarry-Alvarado, J. M., Hurtado Andrade, M. D., Mendez, C. E., Kelley, K. D., Stewart, E., Fernandez Robles, C. R., et al. (2025) · British Journal of Anaesthesia · doi:10.1016/j.bja.2025.04.001 · Cited by 104 · see citing works
The expanding landscape of GLP-1 medicines
Drucker, D. J. (2026) · Nature Medicine · doi:10.1038/s41591-025-04124-5 · Cited by 70 · see citing works
The future of type 1 diabetes therapy
Ziegler, A.-G., Cengiz, E., & Kay, T. W. H. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01438-2 · Cited by 42 · see citing works
Infante, M., Silvestri, F., Padilla, N., Pacifici, F., Pastore, D., Pinheiro, M. M., Caprio, M., Tesauro, M., Fabbri, A., Novelli, G., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14041303 · Cited by 16 · see citing works
“Moreover, a multicenter, double-blind, parallel-group trial found that liraglutide treatment leads to significant preservation of residual beta-cell function and reduction in daily insulin requirements during the first year after diagnosis in patients with new-onset T1D [100].”
Glucagon-like peptide-1 receptor agonists and type 1 diabetes: a potential game changer?
Resnick, O., Bril, F., & Beauchamp, G. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1520313 · Cited by 20 · see citing works
The effects of GLP-1 agonists on HbA1c and insulin dose among patients with type 1 diabetes
Alhowiti, A., & Mirghani, H. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1550938 · Cited by 9 · see citing works
Garg, S. K., Aktürk, H. K., Garg, S., Beck, R. W., Bellini, N. J., Bjornstad, P., Carlson, A. L., Carroll, J., Close, K., Block, C., et al. (2026) · Diabetes Technology & Therapeutics · doi:10.1177/15209156261449879 · Cited by 6 · see citing works
“34 – 37 Despite more than a century passing since the discovery of insulin, there remain no other approved adjunctive treat-ment options available for people with T1D and over-weight/obesity who need improved glycemic management, glucose stability, and protection from diabetes-related complications.”
Safety of GLP-1 receptor agonists in type 1 diabetes: a systematic review and meta-analysis.
Kateel, R., Parida, A., Chogtu, B., & Holla, S. N. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113270 · Cited by 5 · see citing works
The evolution of C-peptide's role in diabetes care
Briggs, L., Read, A., Darch, S. J., Williams, E. L., Loh, W. J., & Kenkre, J. S. (2025) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000947 · Cited by 6 · see citing works
Chen, Y., Tang, Y.-F., Yue, R., Yang, B., Wang, A.-H., Long, Y., Xu, Y., & Gao, C.-L. (2025) · Diabetes/Metabolism Research Reviews · doi:10.1002/dmrr.70111 · Cited by 5 · see citing works
Autoimmune Type 1 Diabetes in the Era of Disease‐Modifying Immune Therapy
Michels, A. W., Gottlieb, P. A., Nelson, B., & Dayan, C. M. (2025) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.70091 · Cited by 6 · see citing works
Noninsulin Therapies in Management of Type 1 Diabetes
Saeed, Z. I., Ambalavanan, J., Rayan, M. N., Patadia, P., & Shah, V. N. (2025) · Endocrine Practice · doi:10.1016/j.eprac.2025.06.027 · Cited by 5 · see citing works
Abdel‐Rahman, S. M., Al-Shiab, R., Shah, E., Güldan, M., Ak, A. B., Yilmaz, Z. Y., Fidan, D. G., Özbek, L., & Kanbay, M. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.70506 · Cited by 7 · see citing works
Nwosu, B. U. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1462249 · Cited by 4 · see citing works
Advances in Microneedle Drug Delivery for Obesity: Mechanisms, Applications, and Perspectives
Wu, C., Zong, Z., Hua, F., Wu, J., Shen, Y., Tian, Y., & Chen, Y. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s566132 · Cited by 4 · see citing works
Litus, E., Shevelyova, M., Vologzhannikova, A., Deryusheva, E. I., Chaplygina, A. V., Rastrygina, V. A., Machulin, A., Alikova, V. D., Nazipova, A. A., Permyakova, M. E., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094095 · Cited by 3 · see citing works
Mirghani, H., Albishi, L. A., & Alblewi, S. M. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1758755 · Cited by 2 · see citing works
Lawaetz, T. W. H., Kücük, Z., Andersen, T. H., Jensen, A. K., & Johannesen, J. (2025) · Pediatric Diabetes · doi:10.1155/pedi/1633755 · Cited by 1 · see citing works
“…T1D with low c-peptide levels [39 – 42] and might only be bene fi cial for the patients being early in their disease progression as these patients might still have receptor expression, potentially explaining why this group also seem to be the best therapeutic responders in clinical studies [43, 44].”
Hirai, T., Kitada, M., Endo, K., Hayashi, K., & Suzuki, T. (2025) · Cureus · doi:10.7759/cureus.96335 · Cited by 1 · see citing works
Mechanisms of Hepatic Insulin Resistance and Its Contribution to the Pathogenesis of Type 2 Diabetes
Onyango, A. N. (2026) · Comprehensive physiology · doi:10.1002/cph4.70285
Caballero-Corbalán, J., Lundkvist, P., Espes, D., & Carlsson, P. (2026) · Diabetes Obesity and Metabolism · doi:10.1111/dom.71204
Innes, R., Petrie, J., & Dejgaard, T. (2026) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2026.04.002
Self-citationGLP-1 Receptor Agonists May Reduce Insulin Requirements in New-Onset Type 1 Diabetes.
Gregory, J. (2026) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2026.04.010
Fernandes, S., Hettinger, B., Ang, L., & Pop-Busui, R. (2026) · Endocrinology and metabolism clinics of North America (Print) · doi:10.1016/j.ecl.2026.04.007
Pipella, J., & Thompson, P. J. (2026) · Diabetes, obesity and metabolism · doi:10.1111/dom.70711
“Importantly, studies indicate that tirzepatide could modify disease progression by preserving stimulated C-peptide secretion, reducing insulin requirements, and extending the remission period, though long-term randomized trials are needed to validate these effects [60, 61].”
Metabolic dysfunction and the use of adjunct medications in type 1 diabetes
Luk, A., Cheah, Y. S., Misra, S., & Salem, V. (2026) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000956
Stopyra, M., Feret, K., Andrzejczyk, A., Nafalska, N., Tomaszewska, A., Gadzinowska, J., Kokoszka, M., Chodór, M., Szpila, G., & Lewandowska, A. (2025) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(47).2025.3970
Letter: Tirzepatide in Type 1 Diabetic Obese Patient Using Hybrid Closed-Loop
Baretić, M. (2025) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2025.0245
- Authors
- Dejgaard, T. F., Frandsen, C. S., Kielgast, U., Størling, J., Overgaard, A. J., Svane, M. S., Olsen, M. H., Thorsteinsson, B., Andersen, H. U., Krarup, T., Holst, J. J., & Madsbad, S.
- Affiliations
- University of Copenhagen (DK)
- Hvidovre Hospital (DK)
- Copenhagen University Hospital (DK)
- Steno Diabetes Center Copenhagen (DK)
- Corresponding author
- Madsbad, Sten
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2024-08-27
- Volume
- 26
- Issue
- 11
- Pages
- 4905-4915
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4401968110
- Cited by
- 29
- References
- 31
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 1 · 2022: 1
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- liraglutide, type 1 diabetes, newly diagnosed diabetes, GLP-1 receptor agonists, residual beta-cell function, C-peptide, insulin secretion, insulin dose reduction, remission, hypoglycemia, mixed meal tolerance test
- MeSH terms
- Liraglutide, Insulin Secretion, Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Remission Induction, Treatment Outcome, Area Under Curve, Insulin-Secreting Cells
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
