{ "abstract": "Purpose: To compare glycemic and weight effects of fixed-ratio combinations (FRCs) of basal insulin (BI) and glucagon-like peptide-1 receptor agonists (GLP1RAs) in adults with type 2 diabetes (T2D).\n\nMethods: Randomized controlled trials of BI–GLP1RA FRCs in adults with T2D were identified across major databases through 20 December 2025. Co-primary outcomes were changes in glycated hemoglobin (HbA1c) and body weight. A frequentist random-effects network meta-analysis, with BI as the reference, was conducted in R using netmeta. Certainty was assessed using Confidence in Network Meta-Analysis (CINeMA).\n\nResults: Thirty trials involving 17,862 participants were included. All FRCs reduced HbA1c and body weight more than BI alone. For HbA1c, HR17031 had the largest estimated reduction (mean difference [MD]: -0.72%), followed by IDegLira (-0.64%) and iGlarLixi (-0.53%). For body weight, IcoSema had the largest estimated reduction (-3.16 kg), followed by HR17031 (-1.74 kg) and IDegLira (-1.65 kg). No HR17031 comparison with other FRCs was statistically significant for either co-primary outcome; its ranking is hypothesis-generating. Excluding the high-risk-of-bias trial produced broadly consistent estimates. Compared with BI, FRCs increased achievement of HbA1c < 7%, often without weight gain or clinically significant/severe hypoglycemia. CINeMA indicated predominantly low- to moderate-certainty evidence for FRC versus BI comparisons and low- to very low-certainty evidence for many indirect comparisons among active regimens.\n\nConclusions: BI–GLP1RA FRCs improve glycemic control and weight outcomes compared with BI alone. Rankings and apparent differences among FRCs or versus other active regimens warrant cautious interpretation given heterogeneity, inconsistency, and limited certainty of indirect evidence.\n\nGraphical Abstract: This image summarizes a network meta-analysis of 30 randomized controlled trials comparing fixed-ratio combinations of basal insulin and GLP1 receptor agonists to basal insulin alone or other comparators in adults with type 2 diabetes and inadequate control. The key findings are that fixed-ratio combinations provide greater benefit in reducing HbA1c levels and achieving HbA1c below 7 percent, while also presenting less risk of weight gain and hypoglycemia. The conclusion states that fixed-ratio combinations offer superior glycemic control and weight loss compared to basal insulin alone, are generally more effective than other regimens without causing weight gain or hypoglycemia, and that high heterogeneity in results indicates a need for further direct comparison trials.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s12020-026-04857-4.", "abstract_shown": true, "affiliations": [ "Department of Endocrinology, Mymensingh Medical College, Mymensingh, 2200 Bangladesh", "Department of Endocrinology, NRS Medical College, 138 AJC Bose Road, Kolkata, 700014 West Bengal India", "Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru, 570015 Karnataka India", "Department of Medicine, Ibrahim Khalil, MBBS, Dhaka Medical College and Hospital, Dhaka, 1000 Bangladesh", "Department of Endocrinology, CEDAR Superspeciality Healthcare, Dwarka, Delhi 110075 New Delhi, India", "Department of Endocrinology, Countess of Chester Hospital NHS Trust, CH2 2AZ Chester, UK", "Faculty of Science, Manchester Metropolitan University, Manchester, Greater Manchester, M15 6BH UK", "Department of Endocrinology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal, Manipal, 576104 Karnataka India" ], "article_type": "review article", "arxiv": null, "author_total": 6, "authors": [ { "affs": [ 0 ], "name": "A B M Kamrul-Hasan", "orcid": "0000-0002-5681-6522" }, { "affs": [ 1 ], "name": "Sunetra Mondal", "orcid": "0000-0003-3064-466X" }, { "affs": [ 2 ], "name": "Lakshmi Nagendra", "orcid": "0000-0001-6865-5554" }, { "affs": [ 3 ], "name": "Ibrahim Khalil", "orcid": "0009-0002-8995-1058" }, { "affs": [ 4 ], "name": "Deep Dutta", "orcid": "0000-0003-4915-8805" }, { "affs": [ 5, 6, 7 ], "name": "Joseph M Pappachan", "orcid": "0000-0003-0886-5255" } ], "bibtex": "https://research.draconitic.com/paper/0h04c8hqyj44r.bib", "cited_by": 0, "doi": "10.1007/s12020-026-04857-4", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723511/", "id": "0h04c8hqyj44r", "issns": [ "1355-008X", "1559-0100" ], "landing_url": "https://doi.org/10.1007/s12020-026-04857-4", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Systematic Review" ], [ "openalex", "2712|Diabetes Treatment and Management" ] ], "openalex": "W7224997792", "pdf_url": "https://link.springer.com/content/pdf/10.1007/s12020-026-04857-4.pdf", "pmcid": "PMC13723511", "pmid": "42965609", "published": "2026-10-31", "publisher": null, "ris": "https://research.draconitic.com/paper/0h04c8hqyj44r.ris", "sources": [ { "first_seen": "2026-11-04T12:22:08Z", "native_id": "PMC13723511", "source": "pmc", "url": "https://doi.org/10.1007/s12020-026-04857-4" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2712|Diabetes Treatment and Management", "subfield": "endocrinology-metabolism" } ], "title": "Glycemic control and weight loss benefits of fixed-ratio combinations of basal insulins and GLP1 receptor agonists in type 2 diabetes: A systematic review and network meta-analysis", "title_text": "Glycemic control and weight loss benefits of fixed-ratio combinations of basal insulins and GLP1 receptor agonists in type 2 diabetes: A systematic review and network meta-analysis", "type": "peer-reviewed", "updated_at": "2026-11-05T12:20:19Z", "url": "https://research.draconitic.com/paper/0h04c8hqyj44r", "venue": "Endocrine", "versions": [] }