Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND)

Summary

The purpose of this trial is to assess whether dulaglutide can reduce major cardiovascular events and other serious outcomes in persons with type 2 diabetes, when added to their anti-hyperglycemic regimen.

Timeline

Start

2011-07-22

Primary completion

2018-08-21

Completion

2018-08-21

Outcome

Met primary endpoint

registry Placebo vs Dulaglutide; p = 0.026; Hazard Ratio (HR) 0.88 (95.33% CI 0.79 to 0.99) NCT01394952 ↗

release “The company announced that Trulicity® met the primary efficacy objective in the REWIND clinical trial” lilly.com ↗

release “Detailed results from REWIND, the Trulicity® (dulaglutide) cardiovascular outcome trial, showed a significant 12 percent reduction in major cardiovascular events (MACE)” lilly.com ↗

Publications

• Wilson JM, Dage JL, Qian HR, Irelan CL, Crowder HS, Duffin KL, Mintun M, Brooks DA, Gerstein HC, Bethel MA. Dulaglutide and neurodegeneration biomarkers: REWIND post hoc analysis. Alzheimers Dement. 2026 Apr;22(4):e71391. doi: 10.1002/alz.71391.
• Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
• Gerstein HC, Lee SF, Pare G, Bethel MA, Colhoun HM, Hoover A, Lakshmanan M, Lin Y, Pirro V, Qian HR, Ruotolo G, Ryden L, Wilson JM, Duffin KL. Biomarker Changes Associated With Both Dulaglutide and Cardiovascular Events in the REWIND Randomized Controlled Trial: A Nested Case-Control Post Hoc Analysis. Diabetes Care. 2023 May 1;46(5):1046-1051. doi: 10.2337/dc22-2397.
• Ferrannini G, Maldonado JM, Raha S, Rao-Melacini P, Khatun R, Atisso C, Shurzinske L, Gerstein HC, Ryden L, Bethel MA. Gender differences in cardiovascular risk, treatment, and outcomes: a post hoc analysis from the REWIND trial. Scand Cardiovasc J. 2023 Dec;57(1):2166101. doi: 10.1080/14017431.2023.2166101.
• Gerstein HC, Ramasundarahettige C, Avezum A, Basile J, Conget I, Cushman WC, Dagenais GR, Franek E, Lakshmanan M, Lanas F, Leiter LA, Pogosova N, Probstfield J, Raubenheimer PJ, Riddle M, Shaw J, Sheu WH, Temelkova-Kurktschiev T, Turfanda I, Xavier D. A novel kidney disease index reflecting both the albumin-to-creatinine ratio and estimated glomerular filtration rate, predicted cardiovascular and kidney outcomes in type 2 diabetes. Cardiovasc Diabetol. 2022 Aug 22;21(1):158. doi: 10.1186/s12933-022-01594-6.
• Franek E, Gerstein HC, Riddle MC, Nicolay C, Hickey A, Botros FT, Loo LS. Efficacy and safety outcomes of dulaglutide by baseline HbA1c: A post hoc analysis of the REWIND trial. Diabetes Obes Metab. 2022 Sep;24(9):1753-1761. doi: 10.1111/dom.14760. Epub 2022 May 30.
• Cukierman-Yaffe T, Gerstein HC, Basile J, Bethel MA, Cardona-Munoz EG, Conget I, Dagenais G, Franek E, Hall S, Hancu N, Jansky P, Lakshmanan M, Lanas F, Leiter LA, Lopez-Jaramillo P, Pirags V, Pogosova N, Probstfield J, Rao-Melacini P, Ramasundarahettige C, Raubenheimer PJ, Riddle MC, Ryden L, Shaw JE, Sheu WH, Temelkova-Kurktschiev T. Novel Indices of Cognitive Impairment and Incident Cardiovascular Outcomes in the REWIND Trial. J Clin Endocrinol Metab. 2022 Jul 14;107(8):e3448-e3454. doi: 10.1210/clinem/dgac200.
• Kwan AYM, Gerstein HC, Basile J, Xavier D, Maldonado JM, Raha S, Konig M. HbA1c Reduction in Dulaglutide-Treated Patients Irrespective of Duration of Diabetes, Microvascular Disease, and BMI: A Post Hoc Analysis From the REWIND Trial. Diabetes Care. 2022 Mar 1;45(3):547-554. doi: 10.2337/dc21-1160.
• Konig M, Riddle MC, Colhoun HM, Branch KR, Atisso CM, Lakshmanan MC, Mody R, Raha S, Gerstein HC. Exploring potential mediators of the cardiovascular benefit of dulaglutide in type 2 diabetes patients in REWIND. Cardiovasc Diabetol. 2021 Sep 25;20(1):194. doi: 10.1186/s12933-021-01386-4.
• Bajaj HS, Gerstein HC, Rao-Melacini P, Basile J, Colhoun H, Conget I, Cushman WC, Dagenais GR, Franek E, Hanefeld M, Keltai M, Lakshmanan M, Lanas F, Leiter LA, Lopez-Jaramillo P, Pirags V, Pogosova N, Probstfield J, Raubenheimer P, Ryden L, Shaw JE, Sheu WH, Xavier D. Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial. Lancet Diabetes Endocrinol. 2021 Aug;9(8):484-490. doi: 10.1016/S2213-8587(21)00115-7. Epub 2021 Jun 18.
• Riddle MC, Gerstein HC, Xavier D, Cushman WC, Leiter LA, Raubenheimer PJ, Atisso CM, Raha S, Varnado OJ, Konig M, Lakshmanan M, Franek E. Efficacy and Safety of Dulaglutide in Older Patients: A post hoc Analysis of the REWIND trial. J Clin Endocrinol Metab. 2021 Apr 23;106(5):1345-1351. doi: 10.1210/clinem/dgab065.
• Dagenais GR, Ryden L, Leiter LA, Lakshmanan M, Dyal L, Probstfield JL, Atisso CM, Shaw JE, Conget I, Cushman WC, Lopez-Jaramillo P, Lanas F, Munoz EGC, Pirags V, Pogosova N, Basile J, Sheu WHH, Temelkova-Kurktschiev T, Raubenheimer PJ, Keltai M, Hall S, Pais P, Colhoun HM, Riddle MC, Gerstein HC. Total cardiovascular or fatal events in people with type 2 diabetes and cardiovascular risk factors treated with dulaglutide in the REWIND trail: a post hoc analysis. Cardiovasc Diabetol. 2020 Nov 25;19(1):199. doi: 10.1186/s12933-020-01179-1.
• Cukierman-Yaffe T, Gerstein HC, Colhoun HM, Diaz R, Garcia-Perez LE, Lakshmanan M, Bethel A, Xavier D, Probstfield J, Riddle MC, Ryden L, Atisso CM, Hall S, Rao-Melacini P, Basile J, Cushman WC, Franek E, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T. Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet Neurol. 2020 Jul;19(7):582-590. doi: 10.1016/S1474-4422(20)30173-3.
• Gerstein HC, Hart R, Colhoun HM, Diaz R, Lakshmanan M, Botros FT, Probstfield J, Riddle MC, Ryden L, Atisso CM, Dyal L, Hall S, Avezum A, Basile J, Conget I, Cushman WC, Hancu N, Hanefeld M, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Munoz EGC, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T. The effect of dulaglutide on stroke: an exploratory analysis of the REWIND trial. Lancet Diabetes Endocrinol. 2020 Feb;8(2):106-114. doi: 10.1016/S2213-8587(19)30423-1. Epub 2020 Jan 7.
• Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Ryden L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. Epub 2019 Jun 9.
• Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Botros FT, Riddle MC, Ryden L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019 Jul 13;394(10193):131-138. doi: 10.1016/S0140-6736(19)31150-X. Epub 2019 Jun 9.
• Wittbrodt ET, Eudicone JM, Bell KF, Enhoffer DM, Latham K, Green JB. Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials enrollment criteria to the US type 2 diabetes population. Am J Manag Care. 2018 Apr;24(8 Suppl):S146-S155.
• Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riddle MC, Ryden L, Xavier D, Atisso CM, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona-Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw J, Sheu WH, Temelkova-Kurktschiev T; REWIND Trial Investigators. Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide. Diabetes Obes Metab. 2018 Jan;20(1):42-49. doi: 10.1111/dom.13028. Epub 2017 Jul 14.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Dulaglutide	Peptide	1.5 mg	Subcutaneous

Indications