GLP-1 Evidence

Evidence map

Adverse effects: what the evidence base looks like

9 publications, 7 of them trials and 1 syntheses. This page describes the shape of that literature rather than summarising its conclusions.

Updated 4 min read 9 citations

What the evidence on adverse effects is made of Of 9 publications on this topic, the breakdown by study type: 1 meta-analysis, 7 randomised trial, 1 review. 171meta-analysis (1)randomised trial (7)review (1)
9 publications, by study type. Volume is not strength — the same count can be a settled question or a pile of commentary, and which one it is depends almost entirely on this breakdown. Harvested from PubMed and Crossref; publication type as recorded by the source.

What this literature is made of

There is a real trial literature here, but comparatively little synthesis. Individual trials can disagree, and without meta-analysis it is easy to find one that supports almost any position.

The distinction that matters most is between synthesis and primary research. A meta-analysis pools trials and is the closest thing to a settled answer a field produces. A narrative review is one group's reading of the same material and can be selective without being dishonest. Counting them together, which most citation counts do, obscures exactly the thing you want to know.

When the adverse effects literature was published Publication years for the 9 papers on this topic, grouped into bands from before 2015 through to 2023 onwards. 2023 onwards4 papers2015-20193 papers2020-20222 papers
Still active. The most recent paper here is from 2025, so this is a field where an answer written today may not hold for long. Publication years as recorded by PubMed and Crossref.

How this page is built

Everything above is computed from the citations this site harvested from PubMed and Crossref, not written by hand. When the weekly harvest finds a new paper on this topic, these counts change and the characterisation changes with them. That is the point: a hand-written claim about how strong an evidence base is starts decaying the day it is written.

Publication type is taken as the source records it. That is imperfect — journals label inconsistently, and a paper indexed as a "review" may be a systematic one — so treat the bands as approximate. They are accurate enough to distinguish a trial literature from a commentary literature, which is the distinction that matters.

The strongest work on this topic

Ordered by study design first, then recency. The full set is listed in the references below.

  1. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials30249-9) — Kristensen SL, Rørth R, Jhund PS et al., 2019, meta-analysis
  2. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment — Wharton S, Aronne LJ, Stefanski A et al., 2025, randomised controlled trial
  3. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes — Rosenstock J, Hsia S, Nevarez Ruiz L et al., 2025, randomised controlled trial
  4. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity — Wharton S, Blevins T, Connery L et al., 2023, randomised controlled trial
  5. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes — Frías JP, Davies MJ, Rosenstock J et al., 2021, randomised controlled trial
  6. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial01324-6) — Rosenstock J, Wysham C, Frías JP et al., 2021, randomised controlled trial
  7. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial31149-3) — Gerstein HC, Colhoun HM, Dagenais GR et al., 2019, randomised controlled trial
  8. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept — Coskun T, Sloop KW, Loghin C et al., 2018, randomised controlled trial
  9. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies — Thomsen RW, Mailhac A, Løhde JB et al., 2025, review
How much research is there on adverse effects?
9 publications are indexed here, of which 7 are trials and 1 are syntheses.
Does more research mean a stronger conclusion?
No. Composition matters more than volume — five randomised trials support a claim far better than fifty commentaries, and citation counts do not distinguish between them.
How current is this?
The most recent paper indexed here is from 2025. The set is refreshed weekly from PubMed and Crossref.
Why does this page not tell me the answer?
Because summarising a literature into a conclusion requires reading it, and doing that automatically is how confident nonsense gets published. This page tells you how much weight a conclusion could bear; the articles on this site do the interpreting.

References

Every citation below links to the original peer-reviewed record on PubMed or via DOI. Nothing here is a substitute for medical advice.

  1. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials Kristensen SL, Rørth R, Jhund PS, et al. · The lancet. Diabetes & endocrinology · 2019 · Meta-analysis DOIPubMed 31422062
  2. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist, in Early Type 2 Diabetes Rosenstock J, Hsia S, Nevarez Ruiz L, et al. · The New England journal of medicine · 2025 · Randomised controlled trial DOIPubMed 40544435
  3. Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment Wharton S, Aronne LJ, Stefanski A, et al. · The New England journal of medicine · 2025 · Randomised controlled trial DOIPubMed 40960239
  4. Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity Wharton S, Blevins T, Connery L, et al. · The New England journal of medicine · 2023 · Randomised controlled trial DOIPubMed 37351564
  5. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial Rosenstock J, Wysham C, Frías JP, et al. · Lancet (London, England) · 2021 · Randomised controlled trial DOIPubMed 34186022
  6. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes Frías JP, Davies MJ, Rosenstock J, et al. · The New England journal of medicine · 2021 · Randomised controlled trial DOIPubMed 34170647
  7. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial Gerstein HC, Colhoun HM, Dagenais GR, et al. · Lancet (London, England) · 2019 · Randomised controlled trial DOIPubMed 31189511
  8. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept Coskun T, Sloop KW, Loghin C, et al. · Molecular metabolism · 2018 · Randomised controlled trial DOIPubMed 30473097Full text
  9. Real-world evidence on the utilization, clinical and comparative effectiveness, and adverse effects of newer GLP-1RA-based weight-loss therapies Thomsen RW, Mailhac A, Løhde JB, et al. · Diabetes, obesity & metabolism · 2025 · Review DOIPubMed 40196933Full text