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Second-Line Therapy for Type 2 Diabetes Management: The Treatment/Benefit Paradox of Cardiovascular and Kidney Comorbidities

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posted on 30.07.2021, 14:19 authored by Rozalina G. McCoy, Holly K. Van Houten, Pinar Karaca Mandic, Joseph S. Ross, Victor M. Montori, Nilay D. Shah
Objective: To examine whether GLP-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLT2i) are preferentially initiated among patients with cardiovascular disease, heart failure (HF), or nephropathy, where these drug classes have established benefit, as compared to DPP-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 de-identified 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, as compared to DPP-4i, for those with 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 to 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.


This effort was funded by the National Institute of Diabetes and Digestive and Kidney Diseases grant K23DK114497 (McCoy), AHRQ's Comparative Health System Performance Initiative grant 1U19HS024075 (Shah), and AHRQ’s grant R01HS025164 (Karaca-Mandic). Study contents are the sole responsibility of the authors and do not necessarily represent the official views of NIH.