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Cited by 39Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Contemporary trends in the utilization of second‐line pharmacological therapies for type 2 diabetes in the United States and the United Kingdom

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Abrahami, Devin, D'Andrea, Elvira, Yin, Hui, Kim, Seoyoung C., Paik, Julie M., Wexler, Deborah, Azoulay, Laurent, Patorno, Elisabetta·2023·Diabetes, Obesity and Metabolism
DOI 10.1111/dom.15196PMC PMC10527897
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Abstract

Aim: To examine trends of second‐line glucose‐lowering therapies among patients with type 2 diabetes (T2D) initiating first‐line metformin in the United States and the United Kingdom, overall and by subgroups of cardiovascular disease (CVD) and calendar time. Methods: Using the US Optum Clinformatics and the UK Clinical Practice Research Datalink, we identified adults with T2D who initiated first‐line metformin or sulphonylurea monotherapy, separately, from 2013 to 2019. Within both cohorts, we identified patterns of second‐line medications through June 2021. We stratified patterns by CVD and calendar time to investigate the impact of rapidly evolving treatment guidelines. Results: We identified 148 511 and 169 316 patients initiating treatment with metformin monotherapy in the United States and the United Kingdom, respectively. Throughout the study period, sulphonylureas and dipeptidyl peptidase‐4 inhibitors were the most frequently initiated second‐line medications in the United States (43.4% and 18.2%, respectively) and the United Kingdom (42.5% and 35.8%, respectively). After 2018, sodium‐glucose co‐transporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists were more commonly used as second‐line agents in the United States and the United Kingdom, although these agents were not preferentially prescribed among patients with CVD. Initiation of first‐line sulphonylureas was much less common, and most sulphonylurea initiators had metformin added as the second‐line agent. Conclusions: This international cohort study shows that sulphonylureas remain the most common second‐line medications prescribed following metformin in both the United States and the United Kingdom. Despite recommendations, the use of newer glucose‐lowering therapies with cardiovascular benefits remains low.

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  • SGLT-2 inhibitors are also used at a disease stage similar to GLP-1 receptor agonists and have not been associated with the outcome.

    “We chose SGLT-2 inhibitors as the secondary comparator because they are also used at a disease stage similar to GLP-1 receptor agonists and have not been associated with the outcome.1 6”

    From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [1]

    The Introduction (page unavailable) describes both SGLT-2 inhibitors and GLP-1 receptor agonists as second- or third-line treatments, and the Results report both being prescribed as second-line treatments. This supports use at a similar disease stage. The paper does not identify the citing sentence’s outcome or establish that SGLT-2 inhibitors have not been associated with it. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • DPP-4 inhibitors are not associated with the outcome and are used at a similar disease stage to GLP-1 receptor agonists.

    “We selected DPP-4 inhibitors as the comparator because they are not associated with the outcome and are used at a similar disease stage to GLP-1 receptor agonists1 6 8 27; furthermore, DPP-4 inhibitors and GLP-1 receptor agonists entered the UK market in the same year.”

    From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [1]

    The Introduction (page not provided) describes both DPP-4 inhibitors and GLP-1 receptor agonists as second- or third-line treatments, supporting their use at a similar treatment stage. The paper does not establish that DPP-4 inhibitors are unassociated with the citing document’s unspecified outcome; its statement that they have a neutral effect on weight cannot verify that broader claim. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Authors
Abrahami, D., D'Andrea, E., Yin, H., Kim, S. C., Paik, J. M., Wexler, D., Azoulay, L., & Patorno, E.
Affiliations
  • Brigham and Women's Hospital (US)
  • Division of Pharmacoepidemiology, Department of Medicine Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts USA
  • Jewish General Hospital (CA)
  • Harvard University (US)
Corresponding author
Patorno, Elisabetta
ORCID
Venue
Diabetes, Obesity and Metabolism
Publisher
Wiley
Published
2023-07-03
Volume
25
Issue
10
Pages
2980-2988
ISSN
  • 1462-8902 (ISSN-L)
  • 1463-1326
DOI
10.1111/dom.15196
PMC
PMC10527897
OpenAlex
W4382918428
Cited by
39
References
23
Citations by year
2026: 11 · 2025: 13 · 2024: 14 · 2023: 1
FWCI
7.94
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Diabetes Obesity and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Patient-Centered Outcomes Research Institute (DB‐2020C2‐20326)
  • National Institute on Aging (K08AG055670)
  • Food and Drug Administration (5U01FD007213)
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 › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
type 2 diabetes, second-line therapy, metformin, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists, cardiovascular disease, treatment trends, prescribing patterns, treatment guidelines
MeSH terms
Sodium-Glucose Transporter 2 Inhibitors, Adult, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Glucose, United Kingdom, Humans, Hypoglycemic Agents, Metformin, Sulfonylurea Compounds, United States, Cohort Studies, Dipeptidyl-Peptidase IV Inhibitors

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