HbA 1c 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;45:547–554 | https://doi.org/10.2337/dc21-1160 Anita Y.M. Kwan, 1 Hertzel C. Gerstein, 2 Jan Basile, 3 Denis Xavier, 4 Juan M. Maldonado, 1 Sohini Raha, 1 and Manige Konig 1 OBJECTIVE To evaluate participant characteristics and long-term changes in glycated hemo- globin (HbA 1c ) levels in patients treated with dulaglutide 1.5 mg in a post hoc analysis of the Researching cardiovascular Events with a Weekly INcretin in Dia- betes (REWIND) trial. RESEARCH DESIGN AND METHODS Change from baseline in HbA 1c was assessed during and up to 72 months of treat- ment before and after adjustment for duration of diabetes, prior microvascular disease (nephropathy or retinopathy), and BMI. Slope analyses were used to assess the change in HbA 1c during 0–12 months and 12–72 months of therapy. RESULTS HbA 1c was significantly reduced in patients treated with dulaglutide compared with placebo during 72 months of treatment (least-squares mean difference 5 20.61%, P < 0.001), regardless of diabetes duration, prior microvascular disease, and BMI (all interaction P > 0.07). Significant reductions were apparent at all time points and were independent of these baseline characteristics. Slope analyses revealed that the dulaglutide group experienced a higher rate of HbA 1c reduction compared with the placebo group from 0 to 12 months before and after adjustment. The dulaglutide group also experienced a higher rate of HbA 1c increase from 12 to 72 months com- pared with the placebo group that became nonsignificant after adjustment for diabe- tes duration, prior microvascular disease, and BMI combined. Despite the greater rate of HbA 1c increase in the dulaglutide group during this period, mean HbA 1c values remained below baseline in the dulaglutide group and below mean HbA 1c values in the placebo group. CONCLUSIONS Dulaglutide 1.5-mg treatment was statistically associated with a long-lasting decrease in HbA 1c over 72 months, irrespective of baseline duration of diabetes, microvascular disease, and BMI. Glucose lowering reduces symptoms of hyperglycemia and many of the long-term complications of diabetes (1). Patient characteristics may affect the glycemic responses 1 Eli Lilly and Company, Indianapolis, IN 2 Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada 3 Medical University of South Carolina, Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 4 St. Johns Medical College and Research Institute, Bangalore, India Correspondence: Manige Konig, konig_manige@ lilly.com Received 1 June 2021 and accepted 19 December 2021 Clinical trial reg. no. NCT01394952, clinicaltrials. gov This article contains supplementary material online at https://doi.org/10.2337/figshare.17380850. © 2022 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www. diabetesjournals.org/journals/pages/license. CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL Diabetes Care Volume 45, March 2022 547 Downloaded from http://diabetesjournals.org/care/article-pdf/45/3/547/715853/dc211160.pdf by guest on 30 June 2023