Second-Line Therapy for Type 2 Diabetes Management: The Treatment/Benefit Paradox of Cardiovascular and Kidney Comorbidities
Open accessAbstract
OBJECTIVE: To examine whether glucagon-like peptide 1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) are preferentially initiated among patients with cardiovascular disease, heart failure (HF), or nephropathy, where these drug classes have established benefit, compared with dipeptidyl peptidase 4 inhibitors (DPP-4i), for which corresponding benefits have not been demonstrated. RESEARCH DESIGN AND METHODS: We retrospectively analyzed claims of adults with type 2 diabetes included in OptumLabs Data Warehouse, a deidentified database of commercially insured and Medicare Advantage beneficiaries, who first started GLP-1RA, SGLT2i, or DPP-4i therapy between 2016 and 2019. Using multinomial logistic regression, we examined the relative risk ratios (RRR) of starting GLP-1RA and SGLT2i compared with DPP-4i for those with a history of myocardial infarction (MI), cerebrovascular disease, HF, and nephropathy after adjusting for demographic and other clinical factors. RESULTS: We identified 75,395 patients who started GLP-1RA, 58,234 who started SGLT2i, and 91,884 who started DPP-4i. Patients with prior MI, cerebrovascular disease, or nephropathy were less likely to start GLP-1RA rather than DPP-4i compared with patients without these conditions (RRR 0.83 [95% CI 0.78–0.88] for MI, RRR 0.77 [0.74–0.81] for cerebrovascular disease, and RRR 0.87 [0.84–0.91] for nephropathy). Patients with HF or nephropathy were less likely to start SGLT2i (RRR 0.83 [0.80–0.87] for HF and RRR 0.57 [0.55–0.60] for nephropathy). Both medication classes were less likely to be started by non-White and older patients. CONCLUSIONS: Patients with cardiovascular disease, HF, and nephropathy, for whom evidence suggests a greater likelihood of benefiting from GLP-1RA and/or SGLT2i therapy, were less likely to start these drugs. Addressing this treatment/benefit paradox, which was most pronounced in non-White and older patients, may help reduce the morbidity associated with these conditions.
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.
Integrity signals
Registry
Cites
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.
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?
Use of SGLT2 inhibitors and GLP-1 receptor agonists is paradoxically lower among patients with evidence of or increased risk factors for cardiovascular disease.
“Despite these recommendations, data from studies in the clinical setting show that use of these newer drug classes have been paradoxically lower among patients with evidence of, or increased risk factors for, CVD.3,4,5,6”
From Evaluation of Out-of-Pocket Costs and Treatment Intensification With an SGLT2 Inhibitor or GLP-1 RA in Patients With Type 2 Diabetes and Cardiovascular Disease (2023) · cites this paper as [4]
The Results report that patients with prior myocardial infarction or cerebrovascular disease were less likely to start a GLP-1 receptor agonist than a DPP-4 inhibitor, and that patients with heart failure or nephropathy were less likely to start an SGLT2 inhibitor. This supports the treatment/benefit paradox for those specific conditions, but the study does not establish lower use of both drug classes across patients with cardiovascular risk factors generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrevious research has highlighted a pattern of treatment disparities that is consistent across various data sources.
“Previous research has highlighted a pattern of treatment disparities that is consistent across various data sources [12–17].”
The Elixhauser Comorbidity Index includes 30 comorbid condition measures and has been used to assess prevalent comorbid conditions in health research for examining medication use.
“The Elixhauser Comorbidity Index includes a comprehensive set of 30 comorbid condition measures (covering acute and chronic conditions) and has been used to assess prevalent comorbid conditions in health research for examining medication use.18,22”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [22]
The Introduction describes assessing comorbidities in a study of glucose-lowering medication choice, but names the Diabetes Complications Severity Index and selected individual conditions, not the Elixhauser Comorbidity Index. Searches for “Elixhauser” and “30 comorbid condition measures” found no passage addressing the index’s composition or its use for this purpose. (LLM, conf=0.73)
Experimental — accuracy not yet measuredZip code-level household data are commonly used in Medicare studies.
“Zip code–level household data are commonly used in Medicare studies.18,22”
From Disparities in SGLT2 Inhibitor or Glucagon-Like Peptide 1 Receptor Agonist Initiation Among Medicare-Insured Adults With CKD in the United States (2023) · cites this paper as [22]
The Introduction describes claims data for commercial and Medicare Advantage enrollees and lists patient demographics, but does not mention ZIP code–level household data. Searches for ZIP code, household income, and census data found no passage addressing whether such data are commonly used in Medicare studies. (LLM, conf=0.73)
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.
The citation lists haven’t been fetched yet
References 35 · Cited by 57
Research works printed but not linked: 4
- [1]1. Centers for Disease Control and Prevention . National Diabetes Statistics Report, 2020. Atlanta, Georgia, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2020 [Google Scholar]
- [21]21. OptumLabs . OptumLabs and OptumLabs Data Warehouse (OLDW). Cambridge, MA: May 2019 [Google Scholar]
- [24]24. Chang HY, Weiner JP, Richards TM, Bleich SN, Segal JB. Validating the adapted Diabetes Complications Severity Index in claims data. Am J Manag Care 2012;18:721–726 [PubMed] [Google Scholar]
- [32]32. Centers for Disease Control and Prevention . National Diabetes Statistics Report, 2017. Atlanta, GA, Centers for Disease Control and Prevention, US Department of Health and Human Services, 2017 [Google Scholar]
- Authors
- McCoy, R. G., Van Houten, H. K., Karaca-Mandic, P., Ross, J. S., Montori, V. M., & Shah, N. D.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Rochester, MN
- Department of Finance and Medical Industry Leadership Institute, Carlson School of Management, University of Minnesota, Minneapolis, MN
- Yale New Haven Hospital (US)
- Division of Endocrinology, Diabetes, Metabolism, & Nutrition, Department of Medicine, Mayo Clinic
- Corresponding author
- McCoy, Rozalina G.
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2021-08-04
- Volume
- 44
- Issue
- 10
- Pages
- 2302-2311
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC8929191
- OpenAlex
- W3189046973
- Cited by
- 57
- References
- 35
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 19 · 2023: 15 · 2022: 10 · 2021: 1
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR001863)
- U.S. Food and Drug Administration (U01 FD004585, U01FD005938)
- Agency for Healthcare Research and Quality (R03 HS025517, U19 HS024075, R01 HS025402, R01 HS025164, R01HS022882)
- National Institute on Aging (P01AG005842)
- National Heart, Lung, and Blood Institute (R56HL130496, R01HL131535)
- National Institute of Diabetes and Digestive and Kidney Diseases (K23DK114497, P30DK111024)
- National Center for Advancing Translational Sciences
- 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 › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, second-line therapy, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, cardiovascular comorbidity, heart failure, diabetic nephropathy, myocardial infarction, cerebrovascular disease
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
