Glucagon‐like peptide‐1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta‐analysis
Open accessAbstract
Aims: Since 2005, several glucagon‐like peptide‐1 receptor agonists ( GLP ‐1 RAs ) have been approved to treat people with type 2 diabetes. These agents are considered for use at the same point in the treatment paradigm as basal insulins. A comprehensive comparison of these drug classes, therefore, can help inform treatment decisions. This systematic review and meta‐analysis assessed the clinical efficacy and safety of GLP ‐1 RAs compared with basal insulins. Materials and methods: MEDLINE , EMBASE , CENTRAL and PubMed databases were searched. Randomized clinical trials ( RCTs ) of ≥16 weeks’ duration comparing GLP ‐1 RAs vs basal insulins in adults with type 2 diabetes inadequately controlled with oral antihyperglycemic drugs were included. Data on the change from baseline to 26 weeks (±10 weeks) of treatment in hemoglobin A1c ( HbA1c ) and weight, as well as the proportion of patients experiencing hypoglycaemia, were extracted. Fixed‐effect pairwise meta‐analyses were conducted where data were available from ≥2 studies. Results: Fifteen RCTs were identified and 11 were meta‐analysed. The once‐weekly GLP ‐1 RAs , exenatide long acting release ( LAR ) and dulaglutide, led to greater, statistically significant mean HbA1c reductions vs basal insulins (exenatide: −0.31% [95% confidence interval −0.42, −0.19], dulaglutide: −0.39% [−0.49, −0.29]) whilst once‐daily liraglutide and twice‐daily exenatide did not (liraglutide: 0.06% [−0.06, 0.18], exenatide: 0.01% [−0.11, 0.13]). Mean weight reduction was seen with all GLP ‐1 RAs while mean weight gain was seen with basal insulins. Interpretation of the analysis of hypoglycaemia was limited by inconsistent definitions and reporting. Because of the limited number of available studies sensitivity analyses to explore heterogeneity could not be conducted. Conclusions: Although weight reduction is seen with all GLP‐1 RA ’s, only the once‐weekly agents, exenatide LAR and dulaglutide, demonstrate significant HbA1c reductions when compared to basal insulins.
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GLP-1 RAs and dual GIP and GLP-1 RA in these trials had beneficial effects on body weight compared with insulin.
“GLP-1 RAs and dual GIP and GLP-1 RA in these trials also had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects.”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [124]
The Discussion reports significant weight loss with all GLP-1 RAs studied, compared with weight gain on basal insulin. The Methods describe trials of GLP-1 RAs versus basal insulin; the paper does not address dual GIP and GLP-1 receptor agonists, so it does not support that part of the claim. Page numbers were not provided in the passages. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIn trials analyzing addition of injectable GLP-1 RA, dual GIP and GLP-1 RA, or insulin in people needing further glucose lowering, glycemic efficacies of GLP-1 RAs and the dual GIP and GLP-1 RA were similar to or greater than that of basal insulin.
“In trials analyzing the addition of an injectable GLP-1 RA, dual GIP and GLP-1 RA, or insulin in people needing further glucose lowering, glycemic efficacies of GLP-1 RAs and the dual GIP and GLP-1 RA were similar to or greater than that of basal insulin (123-130).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [124]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredGLP-1 RAs and dual GIP and GLP-1 RA in these trials had a lower risk of hypoglycemia compared with insulin.
“GLP-1 RAs and dual GIP and GLP-1 RA in these trials also had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects.”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [124]
The Results (Safety outcomes; page unavailable) report lower odds of hypoglycaemia with two GLP-1 receptor agonists than with insulin glargine. The Discussion cautions that differing definitions limit interpretation. This paper does not study dual GIP/GLP-1 receptor agonists, so it cannot support that part of the claim. (LLM, conf=0.90)
Experimental — accuracy not yet measuredGLP-1 RAs and dual GIP and GLP-1 RA in these trials had greater gastrointestinal side effects compared with insulin.
“GLP-1 RAs and dual GIP and GLP-1 RA in these trials also had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects.”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [124]
The Results, under Safety outcomes (page unavailable), say gastrointestinal-event reporting was insufficient for a meaningful analysis; they do not state whether GLP-1 RAs caused more gastrointestinal side effects than insulin. The Results list GLP-1 RAs compared with basal insulins, but no dual GIP/GLP-1 agonist. I searched the copy for gastrointestinal-event comparisons and dual-agonist trials. (LLM, conf=0.77)
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- Authors
- Singh, S., Wright, E. E., Kwan, A. Y. M., Thompson, J. C., Syed, I. A., Korol, E. E., Waser, N. A., Yu, M. B., & Juneja, R.
- Affiliations
- Johns Hopkins University (US)
- Duke Medical Center (US)
- Eli Lilly (United States) (US)
- ICON Epidemiology Vancouver British Columbia Canada
- Eli Lilly (Canada) (CA)
- Corresponding author
- Juneja, Rattan
- ORCID
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2016-12-05
- Volume
- 19
- Issue
- 2
- Pages
- 228-238
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC5299485
- OpenAlex
- W2528138059
- Cited by
- 101
- References
- 44
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 15 · 2023: 12 · 2022: 6 · 2021: 11 · 2020: 16 · 2019: 11 · 2018: 9 · 2017: 5 · 2016: 2
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Boehringer Ingelheim
- Amgen
- 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 › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- GLP-1 receptor agonists, basal insulin, type 2 diabetes, glycemic control, HbA1c reduction, weight loss, hypoglycemia, dulaglutide, liraglutide, exenatide, insulin sensitizers
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Insulin Glargine, Insulin Detemir, Liraglutide, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Blood Glucose, Diabetes Mellitus, Type 2, Glucagon-Like Peptides, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Immunoglobulin Fc Fragments, Insulin, Peptides, Recombinant Fusion Proteins, Venoms, Insulin, Long-Acting, Incretins
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