Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk: The CARMELINA Randomized Clinical Trial
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Importance: Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. Objective: To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. Design, Setting, and Participants: Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A1c of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] >200 mg/g), and high renal risk (reduced eGFR and micro- or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. Interventions: Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. Main Outcomes and Measures: Primary outcome was time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. Results: Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73 m2; 80.1% with UACR >30 mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI, -0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P < .001 for noninferiority). The kidney outcome occurred in 327 of 3494 (9.4%) and 306 of 3485 (8.8%), respectively (absolute incidence rate difference, 0.22 [95% CI, -0.52 to 0.97] per 100 person-years) (HR, 1.04; 95% CI, 0.89-1.22; P = .62). Adverse events occurred in 2697 (77.2%) and 2723 (78.1%) patients in the linagliptin and placebo groups; 1036 (29.7%) and 1024 (29.4%) had 1 or more episodes of hypoglycemia; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis. Conclusions and Relevance: Among adults with type 2 diabetes and high CV and renal risk, linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk of a composite CV outcome over a median 2.2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01897532.
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EXAMINE, TECOS, and CARMELINA did not find a significant increase in risk of heart failure hospitalization with DPP-4 inhibitor use compared with placebo.
“However, three other cardiovascular outcomes trials-Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) (293), Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (294), and the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) (295)-did not find a significant increase in risk of heart failure hospitalization with D”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [295]
Three other cardiovascular outcomes trials-EXAMINE, TECOS, and CARMELINA-did not find a significant increase in risk of heart failure hospitalization with DPP-4 inhibitor use compared with placebo.
“However, three other cardiovascular outcomes trials—Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) (312), Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) (313), and the Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) (314)—did not find a significant increase in risk of heart failure hospitalization with D”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [314]
In CAROLINA, linagliptin was noninferior to glimepiride for cardiovascular outcomes and caused less hypoglycemia.
“In addition, the CAROLINA (Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Type 2 Diabetes) study demonstrated noninferiority between a DPP-4 inhibitor, linagliptin, and a sulfonylurea, glimepiride, on cardiovascular outcomes despite lower rates of hypoglycemia in the linagliptin treatment group (193).”
From 10. Cardiovascular Disease and Risk Management: <i>Standards of Care in Diabetes—2023</i> (2023) · cites this paper as [193]
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Cites
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
(2008) · New England Journal of Medicine · doi:10.1056/nejmoa0802987 · Cited by 7,397 · see citing works
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Nissen, S. E., & Wolski, K. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072761 · Cited by 4,675 · see citing works
Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
Scirica, B. M., Bhatt, D. L., Braunwald, E., Steg, P. G., Davidson, J., Hirshberg, B., Ohman, P., Frederich, R., Wiviott, S. D., Hoffman, E. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1307684 · Cited by 3,470 · see citing works
Self-citationEffect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes
Green, J. B., Bethel, M. A., Armstrong, P. W., Buse, J. B., Engel, S. S., Garg, J., Josse, R., Kaufman, K. D., Koglin, J., Korn, S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501352 · Cited by 2,577 · see citing works
Self-citationAlogliptin after acute coronary syndrome in patients with type 2 diabetes
White, W. B., Cannon, C. P., Heller, S. R., Nissen, S. E., Bergenstal, R. M., Bakris, G. L., Perez, A. T., Fleck, P. R., Mehta, C. R., Kupfer, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305889 · Cited by 2,502 · see citing works
Mortality and cardiovascular disease in type 1 and type 2 diabetes
Rawshani, A., Rawshani, A., Franzén, S., Eliasson, B., Svensson, A.-M., Miftaraj, M., McGuire, D. K., Sattar, N., Rosengren, A., & Gudbjörnsdottir, S. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1608664 · Cited by 1,389 · see citing works
Self-citationIntensive glucose control and macrovascular outcomes in type 2 diabetes
Turnbull, F. M., Abraira, C., Anderson, R. J., Byington, R. P., Chalmers, J. P., Duckworth, W. C., Evans, G. W., Gerstein, H. C., Holman, R. R., Moritz, T. E., et al. (2009) · Diabetologia · doi:10.1007/s00125-009-1470-0 · Cited by 1,189 · see citing works
Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014
Afkarian, M., Zelnick, L. R., Hall, Y. N., Heagerty, P. J., Tuttle, K., Weiss, N. S., & de Boer, I. H. (2016) · JAMA · doi:10.1001/jama.2016.10924 · Cited by 1,026 · see citing works
Zannad, F., Cannon, C. P., Cushman, W. C., Bakris, G. L., Menon, V., Perez, A. T., Fleck, P. R., Mehta, C. R., Kupfer, S., Wilson, C., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)62225-x · Cited by 757 · see citing works
Scirica, B. M., Braunwald, E., Raz, I., Cavender, M. A., Morrow, D. A., Jarolim, P., Udell, J. A., Mosenzon, O., Im, K., Umez-Eronini, A. A., et al. (2014) · Circulation · doi:10.1161/circulationaha.114.010389 · Cited by 725 · see citing works
Self-citationLago, R. M., Singh, P. P., & Nesto, R. W. (2007) · The Lancet · doi:10.1016/s0140-6736(07)61514-1 · Cited by 710 · see citing works
Levey, A. S., Inker, L. A., Matsushita, K., Greene, T., Willis, K., Lewis, E., de Zeeuw, D., Cheung, A. K., & Coresh, J. (2014) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2014.07.030 · Cited by 620 · see citing works
Metformin in Patients With Type 2 Diabetes and Kidney Disease: A Systematic Review
Inzucchi, S. E., Lipska, K. J., Mayo, H., Bailey, C. J., & McGuire, D. K. (2014) · JAMA · doi:10.1001/jama.2014.15298 · Cited by 601 · see citing works
Self-citationNissen, S. E. (2005) · JAMA · doi:10.1001/jama.294.20.joc50147 · Cited by 552 · see citing works
Groop, P., Cooper, M. E., Perkovic, V., Emser, A., Woerle, H., & von Eynatten, M. (2013) · Diabetes Care · doi:10.2337/dc13-0323 · Cited by 293 · see citing works
Self-citationEffect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial
Mosenzon, O., Leibowitz, G., Bhatt, D. L., Cahn, A., Hirshberg, B., Wei, C., Im, K., Rozenberg, A., Yanuv, I., Stahre, C., et al. (2016) · Diabetes Care · doi:10.2337/dc16-0621 · Cited by 267 · see citing works
Johansen, O. E., Neubacher, D., von Eynatten, M., Patel, S. D., & Woerle, H. (2012) · Cardiovascular Diabetology · doi:10.1186/1475-2840-11-3 · Cited by 220 · see citing works
Self-citationMcGuire, D. K., Van de Werf, F., Armstrong, P. W., Standl, E., Koglin, J., Green, J. B., Bethel, M. A., Cornel, J. H., Lopes, R. D., Halvorsen, S., et al. (2016) · JAMA Cardiology · doi:10.1001/jamacardio.2016.0103 · Cited by 217 · see citing works
Self-citationMarx, N., Rosenstock, J., Kahn, S. E., Zinman, B., Kastelein, J. J., Lachin, J. M., Espeland, M. A., Bluhmki, E., Mattheus, M., Ryckaert, B., et al. (2015) · Diabetes and Vascular Disease Research · doi:10.1177/1479164115570301 · Cited by 212 · see citing works
Self-citationCornel, J. H., Bakris, G. L., Stevens, S. R., Alvarsson, M., Bax, W. A., Chuang, L., Engel, S. S., Lópes, R. D., McGuire, D. K., Riefflin, A., et al. (2016) · Diabetes Care · doi:10.2337/dc16-1415 · Cited by 186 · see citing works
Self-citationMcGuire, D. K., Alexander, J. H., Johansen, O. E., Perkovic, V., Rosenstock, J., Cooper, M. E., Wanner, C., Kahn, S. E., Toto, R. D., Zinman, B., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.038352 · Cited by 164 · see citing works
Self-citationDiabetes with early kidney involvement may shorten life expectancy by 16 years
Wen, C. P., Ch, C., Tsai, M. K., Lee, J. H., Lu, P. J., Tsai, S. P., Chen, C., Chen, C. H., Kao, C. W., Tsao, C. K., et al. (2017) · Kidney International · doi:10.1016/j.kint.2017.01.030 · Cited by 154 · see citing works
Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease
Lo, C., Toyama, T., Wang, Y., Lin, J., Hirakawa, Y., Jun, M., Cass, A., Hawley, C. M., Pilmore, H., Badve, S. V., et al. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011798.pub2 · Cited by 153 · see citing works
Self-citationGlucose targets for preventing diabetic kidney disease and its progression
Ruospo, M., Saglimbene, V. M., Palmer, S. C., De Cosmo, S., Pacilli, A., Lamacchia, O., Cignarelli, M., Fioretto, P., Vecchio, M., Craig, J. C., et al. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010137.pub2 · Cited by 111 · see citing works
Nauck, M. A., Jensen, T. J., Rosenkilde, C., Calanna, S., Buse, J. B., & the LEADER Publication Committee on behalf of the LEADER Trial Investigators (2018) · Diabetes Care · doi:10.2337/dc17-1825 · Cited by 94 · see citing works
Rosenstock, J., Perkovic, V., Alexander, J. H., Cooper, M. E., Marx, N., Pencina, M. J., Toto, R. D., Wanner, C., Zinman, B., Baanstra, D., et al. (2018) · Cardiovascular Diabetology · doi:10.1186/s12933-018-0682-3 · Cited by 83 · see citing works
Self-citationMarx, N., McGuire, D. K., Perkovic, V., Woerle, H., Broedl, U. C., von Eynatten, M., George, J. T., & Rosenstock, J. (2017) · Diabetes Care · doi:10.2337/dc17-0068 · Cited by 72 · see citing works
Self-citationGFR Decline as an End Point in Trials of CKD: A Viewpoint From the FDA
Thompson, A., Lawrence, J., & Stockbridge, N. (2014) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2014.09.006 · Cited by 63 · see citing works
Use of incretin agents and risk of acute and chronic pancreatitis: A population‐based cohort study
Knapen, L. M., de Jong, R. G. P. J., Driessen, J. H. M., Keulemans, Y. C. A., van Erp, N. P., Bruin, M. L. D., Leufkens, H. G. M., Croes, S., & de Vries, F. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12833 · Cited by 42 · see citing works
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2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
McDonagh, T. A., Metra, M., Adamo, M., Gardner, R. S., Baumbach, A., Böhm, M., Burri, H., Butler, J., Čelutkienė, J., Chioncel, O., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab368 · Cited by 13,344 · see citing works
2021 ESC Guidelines on cardiovascular disease prevention in clinical practice
Visseren, F. L. J., Mach, F., Smulders, Y. M., Carballo, D., Koskinas, K. C., Bäck, M., Benetos, A., Biffi, A., Boavida, J.-M., Capodanno, D., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab484 · Cited by 6,485 · see citing works
Self-citationDavies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetes Care · doi:10.2337/dci18-0033 · Cited by 3,518 · see citing works
2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.012 · Cited by 2,862 · see citing works
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001063 · Cited by 4,922 · see citing works
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetes Care · doi:10.2337/dci22-0034 · Cited by 2,104 · see citing works
GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art
Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101102 · Cited by 1,647 · see citing works
2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes.
Marx, N., Federici, M., Schütt, K., Müller-Wieland, D., Ajjan, R. A., Antunes, M. J., Christodorescu, R. M., Crawford, C., Di Angelantonio, E., Eliasson, B., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad192 · Cited by 1,642 · see citing works
Self-citationDavies, M. J., D’Alessio, D. A., Fradkin, J., Kernan, W. N., Mathieu, C., Mingrone, G., Rossing, P., Tsapas, A., Wexler, D. J., & Buse, J. B. (2018) · Diabetologia · doi:10.1007/s00125-018-4729-5 · Cited by 1,455 · see citing works
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de Boer, I. H., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2020) · Kidney International · doi:10.1016/j.kint.2020.06.019 · Cited by 1,399 · see citing works
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Rossing, P., Caramori, M. L., Chan, J. C. N., Heerspink, H. J. L., Hurst, C., Khunti, K., Liew, A., Michos, E. D., Navaneethan, S. D., Olowu, W. A., et al. (2022) · Kidney International · doi:10.1016/j.kint.2022.06.008 · Cited by 1,373 · see citing works
Self-citationBuse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., D’Alessio, D. A., & Davies, M. J. (2020) · Diabetes Care · doi:10.2337/dci19-0066 · Cited by 1,192 · see citing works
Davies, M. J., Aroda, V. R., Collins, B. S., Gabbay, R. A., Green, J., Maruthur, N. M., Rosas, S. E., Del Prato, S., Mathieu, C., Mingrone, G., et al. (2022) · Diabetologia · doi:10.1007/s00125-022-05787-2 · Cited by 1,048 · see citing works
Palmer, S. C., Tendal, B., Mustafa, R. A., Vandvik, P. O., Li, S., Hao, Q., Tunnicliffe, D., Ruospo, M., Natale, P., Saglimbene, V., et al. (2021) · BMJ · doi:10.1136/bmj.m4573 · Cited by 679 · see citing works
Type 2 diabetes mellitus in older adults: clinical considerations and management
Bellary, S., Kyrou, I., Brown, J. E., & Bailey, C. J. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00512-2 · Cited by 639 · see citing works
Joseph, J. J., Deedwania, P., Acharya, T., Aguilar, D., Bhatt, D. L., Chyun, D. A., Di Palo, K. E., Golden, S. H., Sperling, L. S., & on behalf of the American Heart Association Diabetes Committee of the Council on Lifestyle and Cardiometabolic Health; Council on Arteriosclerosis, T. A. V. B. C. O. C. C. A. C. O. H. (2022) · Circulation · doi:10.1161/cir.0000000000001040 · Cited by 660 · see citing works
Rosenstock, J., Kahn, S. E., Johansen, O. E., Zinman, B., Espeland, M. A., Woerle, H. J., Pfarr, E., Keller, A., Mattheus, M., Baanstra, D., et al. (2019) · JAMA · doi:10.1001/jama.2019.13772 · Cited by 612 · see citing works
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Di Pino, A., & DeFronzo, R. A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00141 · Cited by 535 · see citing works
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Araki, E., Goto, A., Kondo, T., Noda, M., Noto, H., Origasa, H., Osawa, H., Taguchi, A., Tanizawa, Y., Tobe, K., et al. (2020) · Diabetology International · doi:10.1007/s13340-020-00439-5 · Cited by 545 · see citing works
Buse, J. B., Wexler, D. J., Tsapas, A., Rossing, P., Mingrone, G., Mathieu, C., D’Alessio, D. A., & Davies, M. J. (2020) · Diabetologia · doi:10.1007/s00125-019-05039-w · Cited by 487 · see citing works
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ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Das, S. R., Hilliard, M. E., Isaacs, D., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s010 · Cited by 465 · see citing works
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Drucker, D. J. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnaa011 · Cited by 399 · see citing works
Rosenstock, J., Allison, D., Birkenfeld, A. L., Blicher, T. M., Deenadayalan, S., Jacobsen, J. B., Serusclat, P., Violante, R., Watada, H., Davies, M., et al. (2019) · JAMA · doi:10.1001/jama.2019.2942 · Cited by 421 · see citing works
Self-citationTsapas, A., Avgerinos, I., Karagiannis, T., Malandris, K., Manolopoulos, A., Andreadis, P., Liakos, A., Matthews, D. R., & Bekiari, E. (2020) · Annals of Internal Medicine · doi:10.7326/m20-0864 · Cited by 346 · see citing works
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Arnold, S. V., Bhatt, D. L., Barsness, G. W., Beatty, A. L., Deedwania, P. C., Inzucchi, S. E., Kosiborod, M., Leiter, L. A., Lipska, K. J., Newman, J. D., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000766 · Cited by 304 · see citing works
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Pollock, C., Stefánsson, B., Reyner, D., Rossing, P., Sjöström, C. D., Wheeler, D. C., Langkilde, A. M., & Heerspink, H. J. L. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30086-5 · Cited by 205 · see citing works
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Gladstone, D. J., Lindsay, M. P., Douketis, J., Smith, E. E., Dowlatshahi, D., Wein, T., Bourgoin, A., Cox, J., Falconer, J. B., Graham, B. R., et al. (2022) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2021.127 · Cited by 168 · see citing works
McGuire, D. K., Alexander, J. H., Johansen, O. E., Perkovic, V., Rosenstock, J., Cooper, M. E., Wanner, C., Kahn, S. E., Toto, R. D., Zinman, B., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.038352 · Cited by 164 · see citing works
Self-citationAbd El Aziz, M., Cahyadi, O., Meier, J. J., Schmidt, W. E., & Nauck, M. A. (2020) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13924 · Cited by 160 · see citing works
Ghosh-Swaby, O. R., Goodman, S. G., Leiter, L. A., Cheng, A., Connelly, K. A., Fitchett, D., Jüni, P., Farkouh, M. E., & Udell, J. A. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30038-3 · Cited by 159 · see citing works
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Rodriguez-Gutierrez, R., Gonzalez-Gonzalez, J. G., Zuñiga-Hernandez, J. A., & McCoy, R. G. (2019) · BMJ · doi:10.1136/bmj.l5887 · Cited by 152 · see citing works
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Lipscombe, L., Butalia, S., Dasgupta, K., Eurich, D. T., MacCallum, L., Shah, B. R., Simpson, S., & Senior, P. A. (2020) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2020.08.001 · Cited by 153 · see citing works
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Mechanick, J. I., Farkouh, M. E., Newman, J. D., & Garvey, W. T. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.046 · Cited by 113 · see citing works
Doyle-Delgado, K., Chamberlain, J. J., Shubrook, J. H., Skolnik, N., & Trujillo, J. (2020) · Annals of Internal Medicine · doi:10.7326/m20-2470 · Cited by 111 · see citing works
10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2026
American Diabetes Association Professional Practice Committee for Diabetes*, Bajaj, M., McCoy, R. G., Balapattabi, K., Bannuru, R. R., Bellini, N. J., Bennett, A. K., Beverly, E. A., Briggs Early, K., ChallaSivaKanaka, S., et al. (2026) · Diabetes Care · doi:10.2337/dc26-s010 · Cited by 107 · see citing works
Goldney, J., Sargeant, J. A., & Davies, M. J. (2023) · Diabetologia · doi:10.1007/s00125-023-05988-3 · Cited by 100 · see citing works
Gilbert, R. E., & Thorpe, K. E. (2019) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13754 · Cited by 92 · see citing works
Lin, D. S.-H., Lee, J.-K., & Chen, W.-J. (2021) · Diabetologia · doi:10.1007/s00125-021-05497-1 · Cited by 68 · see citing works
Maiorino, M. I., Longo, M., Scappaticcio, L., Bellastella, G., Chiodini, P., Esposito, K., & Giugliano, D. (2021) · Cardiovascular Diabetology · doi:10.1186/s12933-021-01401-8 · Cited by 72 · see citing works
Patoulias, D. I., Boulmpou, A., Teperikidis, E., Katsimardou, A., Siskos, F., Doumas, M., Papadopoulos, C. E., & Vassilikos, V. (2021) · World Journal of Cardiology · doi:10.4330/wjc.v13.i10.585 · Cited by 70 · see citing works
Persson, F., Bain, S. C., Mosenzon, O., Heerspink, H. J. L., Mann, J. F. E., Pratley, R., Raz, I., Idorn, T., Rasmussen, S., von Scholten, B. J., et al. (2021) · Diabetes Care · doi:10.2337/dc20-1622 · Cited by 71 · see citing works
Glucose-dependent insulinotropic polypeptide (GIP) and cardiovascular disease
Heimbürger, S. M., Bergmann, N. C., Augustin, R., Gasbjerg, L. S., Christensen, M. B., & Knop, F. K. (2020) · Peptides · doi:10.1016/j.peptides.2019.170174 · Cited by 67 · see citing works
Landgraf, R., Aberle, J., Birkenfeld, A. L., Gallwitz, B., Kellerer, M., Klein, H., Müller-Wieland, D., Nauck, M. A., Reuter, H.-M., & Siegel, E. (2019) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1018-9106 · Cited by 62 · see citing works
Perkovic, V., Toto, R., Cooper, M. E., Mann, J. F. E., Rosenstock, J., McGuire, D. K., Kahn, S. E., Marx, N., Alexander, J. H., Zinman, B., et al. (2020) · Diabetes Care · doi:10.2337/dc20-0279 · Cited by 62 · see citing works
Self-citationBertoccini, L., & Baroni, M. G. (2020) · Advances in Experimental Medicine and Biology · doi:10.1007/5584_2020_494 · Cited by 49 · see citing works
Wexler, D. J., de Boer, I. H., Ghosh, A., Younes, N., Bebu, I., Inzucchi, S. E., McGill, J. B., Mudaliar, S., Schade, D., Steffes, M. W., et al. (2023) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2023.1487 · Cited by 39 · see citing works
Self-citationPérez-Belmonte, L. M., Osuna-Sánchez, J., Millán-Gómez, M., López-Carmona, M. D., Gómez-Doblas, J. J., Cobos-Palacios, L., Sanz-Cánovas, J., Barbancho, M. A., Lara, J. P., Jiménez-Navarro, M., et al. (2019) · Annals of Medicine · doi:10.1080/07853890.2019.1613672 · Cited by 36 · see citing works
Incretins and cardiovascular disease: to the heart of type 2 diabetes?
Solini, A., Tricò, D., & Del Prato, S. (2023) · Diabetologia · doi:10.1007/s00125-023-05973-w · Cited by 32 · see citing works
Mann, J. F. E., & Muskiet, M. H. A. (2021) · Kidney International · doi:10.1016/j.kint.2020.08.036 · Cited by 25 · see citing works
Kitada, M., Hirai, T., & Koya, D. (2020) · Diabetology International · doi:10.1007/s13340-020-00444-8 · Cited by 19 · see citing works
Bilal, A., Yi, F., Gonzalez, G. R., Ali, M., Im, K., Ruff, C. T., Thethi, T. K., & Pratley, R. E. (2024) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2024.108783 · Cited by 14 · see citing works
Cardiovascular events in individuals treated with sulfonylureas or dipeptidyl peptidase 4 inhibitors
Turchin, A., Petito, L. C., Hegermiller, E., Carnahan, R., DeVries, A., Goel, S., Lansang, M. C., McDonnell, M. E., Nair, V., Priest, E., et al. (2025) · JAMA Network Open · doi:10.1001/jamanetworkopen.2025.23067 · Cited by 14 · see citing works
Landgraf, R., Aberle, J., Birkenfeld, A. L., Gallwitz, B., Kellerer, M., Klein, H., Müller-Wieland, D., Nauck, M. A., Wiesner, T., & Siegel, E. (2022) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-1624-3449 · Cited by 12 · see citing works
Rabizadeh, S., Tavakoli Ardakani, M. A., Mouodi, M., Bitaraf, M., Shab-Bidar, S., Esteghamati, A., & Nakhjavani, M. (2020) · Advances in Therapy · doi:10.1007/s12325-020-01434-7 · Cited by 8 · see citing works
- Authors
- Rosenstock, J., Perkovic, V., Johansen, O. E., Cooper, M. E., Kahn, S. E., Marx, N., Alexander, J. H., Pencina, M., Toto, R. D., Wanner, C., Zinman, B., Woerle, H. J., Baanstra, D., Pfarr, E., Schnaidt, S., Meinicke, T., George, J. T., von Eynatten, M., McGuire, D. K., & for the CARMELINA Investigators
- Affiliations
- Dallas Diabetes Research Center (US)
- UNSW Sydney (AU)
- Boehringer Ingelheim (Norway) (NO)
- Monash University (AU)
- University of Washington (US)
- Universitätsklinikum Aachen (DE)
- Duke Clinical Research Institute (US)
- The University of Texas Southwestern Medical Center (US)
- Universitätsklinikum Würzburg (DE)
- Mount Sinai Hospital (CA)
- Universität Ulm (DE)
- Boehringer Ingelheim (Netherlands) (NL)
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany
- Corresponding author
- Rosenstock, Julio
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2019-01-01
- Volume
- 321
- Issue
- 1
- Pages
- 69
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC6583576
- OpenAlex
- W2900149048
- Cited by
- 1,084
- References
- 29
- Citations by year
- 2026: 55 · 2025: 81 · 2024: 100 · 2023: 115 · 2022: 137 · 2021: 173 · 2020: 240 · 2019: 170 · 2018: 9 · 2017: 1 · 2016: 1 · 2014: 1
- FWCI
- 117.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- CSL Behring
- Regeneron Pharmaceuticals
- Intarcia Therapeutics
- Tenax Therapeutics
- CryoLife
- Eisai
- Novo Nordisk
- Astellas Pharma
- Servier
- Esperion Therapeutics
- National Institutes of Health
- Genentech
- Medical Research Council
- National Health and Medical Research Council
- Relypsa
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK017047)
- Janssen Research and Development
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- linagliptin, type 2 diabetes, DPP-4 inhibitors, cardiovascular events, major adverse cardiovascular events, cardiovascular safety, chronic kidney disease, renal outcomes, non-inferiority, albuminuria, estimated glomerular filtration rate decline, renal failure, myocardial infarction, stroke, cardiovascular mortality, non-inferiority margin, HbA1c, urine albumin-creatinine ratio
- MeSH terms
- Linagliptin, Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Double-Blind Method, Drug Therapy, Combination, Female, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Kidney Failure, Chronic, Male, Middle Aged, Risk Factors, Proportional Hazards Models, Dipeptidyl-Peptidase IV Inhibitors
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