CoChat
Sign Up
Cited by 14Diabetes Treatment and ManagementHeart Failure Treatment and ManagementBlood Pressure and Hypertension Studies

Effects of newer anti-hyperglycemic agents on cardiovascular outcomes in older adults: systematic review and meta-analysis

Open access
Bilal, Anika, Yi, Fanchao, Gonzalez, Gonzalo Romero, Ali, Mehreen, Im, KyungAh, Ruff, Christian T., Thethi, Tina K., Pratley, Richard E.·2024·Journal of Diabetes and its Complications
DOI 10.1016/j.jdiacomp.2024.108783

Published version of a preprint

Open this paper in CoChat — free accountOpen PDF

Abstract

Aim To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups. Methods PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years). Results For SGLT-2is, five CVOTs (46,969 patients, 45-50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85-0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73-0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79-0.93]) with no difference in subgroups <65 or ≥65 years. For GLP-1RAs, nine CVOTs (n = 64,236, 34-75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83-0.95]), stroke (RR; 0.86 [CI, 0.76-0.97]) and ACM (RR; 0.90 [CI, 0.83-0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years. Four CVOTs (n = 33,063; 35-58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups. Conclusion The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.jdiacomp.2024.108783

Cites

54 of 54 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • DPP-4 inhibitors are relatively weak agents and do not reduce or increase major adverse cardiovascular outcomes generally, and there is no interaction by age-group.

    “DPP-4 inhibitors are relatively weak agents and do not reduce or increase major adverse cardiovascular outcomes generally, and there is no interaction by age-group (121).”

    From 13. Older Adults: Standards of Care in Diabetes—2025 (2025) · cites this paper as [121]

    The DPP-4 results passage (labeled Conclusion; page unavailable) reports no significant difference in MACE versus placebo and no significant interaction between the <65 and ≥65 age groups. The passage following Figure 5 likewise reports no cardiovascular-outcome benefit. Our copy does not characterize DPP-4 inhibitors as “relatively weak agents,” so that part of the attributed claim is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • DPP-4 inhibitors are relatively weak glucose-lowering agents and do not reduce cardiovascular or kidney disease risks like GLP-1 RAs and SGLT2 inhibitors.

    “DPP-4 inhibitors are relatively weak glucose-lowering agents and do not reduce cardiovascular or kidney disease risks like GLP-1 RAs and SGLT2 inhibitors”

    From 13. Older Adults: Standards of Care in Diabetes—2026 (2026) · cites this paper as [130]

    The DPP-4i discussion (page unavailable) reports no reduction in cardiovascular outcomes versus placebo, while the Abstract reports cardiovascular benefits for GLP-1 RAs and SGLT-2 inhibitors. The paper does not establish that DPP-4 inhibitors are relatively weak glucose-lowering agents or compare the drug classes’ effects on kidney disease risk (searched: glycemic efficacy and kidney/renal outcomes). (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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

Flagged first, then by citations

1 of the 55 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. N Engl J Med. 2014;370(16):1514-23.

Cited by

Sorted by citations

Related

Authors
Bilal, A., Yi, F., Gonzalez, G. R., Ali, M., Im, K., Ruff, C. T., Thethi, T. K., & Pratley, R. E.
Affiliations
  • AdventHealth (US)
  • AdventHealth Orlando (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Bilal, Anika
ORCID
Venue
Journal of Diabetes and its Complications
Publisher
Elsevier BV
Published
2024-08
Volume
38
Issue
8
Pages
108783
ISSN
  • 0891-6632 (ISSN-L)
  • 1056-8727
DOI
10.1016/j.jdiacomp.2024.108783
OpenAlex
W4399565073
Cited by
14
References
55
Citations by year
2026: 6 · 2025: 5 · 2024: 3
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Diabetes and its Complications (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Yale University
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Keywords
anti-hyperglycemic agents, cardiovascular safety, older adults, type 2 diabetes, SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, major adverse cardiovascular events, cardiovascular mortality, all-cause mortality, age subgroups, cardiovascular outcome trials, stroke
MeSH terms
Glucagon-Like Peptide-1 Receptor, Sodium-Glucose Transporter 2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Male, Treatment Outcome, Dipeptidyl-Peptidase IV Inhibitors

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