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Purpose: Despite newer type 2 diabetes (T2D) medications, patients do not always achieve metabolic targets, remaining at risk for cardiorenal complications. Therapeutic decisions are generally made by the healthcare team without considering patients' preferences. We aimed to evaluate patients' T2D treatment preference in two Latin-American countries between two different oral medication profiles, one resembling dipeptidyl peptidase-4 inhibitors (DPP4i) and another resembling sodium-glucose cotransporter-2 inhibitors (SGLT2i)., Patients and Methods: In this cross-sectional, multicenter study from June to September 2020, patients with T2D from Argentina and Mexico (n = 390) completed a discrete choice experiment questionnaire to identify preferences between DPP4i (medication profile A) and SGLT2i (medication profile B). The reason behind patients' choice, and the association between their baseline characteristics and their preference were evaluated using logistic regression methods., Results: Most participants (88.2%) preferred SGLT2i's profile. Participants with older age (p = 0.0346), overweight or obesity (p < 0.0001), high blood pressure (BP; p < 0.0001), high total cholesterol (p = 0.0360), and glycosylated hemoglobin (HbA1c) <7% (p = 0.0001) were more likely to choose SGLT2i compared with DPP4i's profile. The most and least important reasons to choose either drug profile were HbA1c reduction and genital infection risk, respectively. The likelihood of selecting the SGLT2i's profile significantly increased in participants with increased body mass index (BMI; odds ratio [OR] = 8.9, 95% confidence interval [CI]: 3.5-22.5, p < 0.05), high BP (OR = 4.9, 95% CI: 1.9-12.4, p < 0.05), and lower education level (OR = 3.6, 95% CI: 1.0-12.6, p < 0.05)., Conclusion: Latin-American patients with T2D preferred medication with a profile resembling SGLT2i over one resembling DPP4i as a treatment option. A patient-centered approach may aid the healthcare team in decision-making for improved outcomes., Competing Interests: JECG, JCGC, PPT, JACC, AAGP, PMM, LR, and ASC have received consulting and/or speaker and/or advisory board fees from AstraZeneca. JCGC, PPT, AFH, JACC, AAGP, PMM, LR, and ASC have received investigators’ fees from AstraZeneca. JECG has received consulting and/or speaker and/or advisory board fees from Novo Nordisk and Abbott (outside the submitted work) and is the President of ALAD (Asociación Latinoamericana de Diabetes). JCGC has received consulting and/or speaker and/or advisory board fees from Novo Nordisk, Sanofi, Merck, Novartis, Takeda, Janssen, and MSD (outside the submitted work). PPT has received speaker and advisory board fees from Novo Nordisk and Boehringer Ingelheim (outside the submitted work). AFH has received speaker and/or advisory board fees from Sanofi, Novo Nordisk, Boehringer Ingelheim, and Medtronic (outside the submitted work). JACC has received speaker and/or advisory board fees from Novo Nordisk, Sanofi, Abbott, and Boehringer Ingelheim (outside the submitted work). AAGP has received advisory board fees from Novo Nordisk, Merck, Novartis, and Sanofi (outside the submitted work). PMM has received speaker and/or advisory board fees from Novo Nordisk, Sanofi, Amgen, and Boehringer Ingelheim (outside the submitted work). LR has received speaker and/or advisory board fees from Roche, Novo Nordisk, and Craveri (outside the submitted work). ASC has received speaker and/or advisory board fees from Novo Nordisk, Merck, Silanes, and Armstrong (outside the submitted work). EVM, LFTG, HC, AE, and VBT are employees of AstraZeneca. HC is a shareholder of AstraZeneca. The authors report no other conflicts of interest in this work., (© 2022 Costa Gil et al.)