Diabetes & Metabolism Journal (Jul 2024)
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
- Jie-Eun Lee,
- Seung Hee Yu,
- Sung Rae Kim,
- Kyu Jeung Ahn,
- Kee-Ho Song,
- In-Kyu Lee,
- Ho-Sang Shon,
- In Joo Kim,
- Soo Lim,
- Doo-Man Kim,
- Choon Hee Chung,
- Won-Young Lee,
- Soon Hee Lee,
- Dong Joon Kim,
- Sung-Rae Cho,
- Chang Hee Jung,
- Hyun Jeong Jeon,
- Seung-Hwan Lee,
- Keun-Young Park,
- Sang Youl Rhee,
- Sin Gon Kim,
- Seok O Park,
- Dae Jung Kim,
- Byung Joon Kim,
- Sang Ah Lee,
- Yong-Hyun Kim,
- Kyung-Soo Kim,
- Ji A Seo,
- Il Seong Nam-Goong,
- Chang Won Lee,
- Duk Kyu Kim,
- Sang Wook Kim,
- Chung Gu Cho,
- Jung Han Kim,
- Yeo-Joo Kim,
- Jae-Myung Yoo,
- Kyung Wan Min,
- Moon-Kyu Lee
Affiliations
- Jie-Eun Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Korea
- Seung Hee Yu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Soonchunhyang University Gumi Hospital, Soonchunhyang University College of Medicine, Gumi, Korea
- Sung Rae Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea
- Kyu Jeung Ahn
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul, Korea
- Kee-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Korea
- In-Kyu Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
- Ho-Sang Shon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Daegu Catholic University Medical Center, Daegu, Korea
- In Joo Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
- Soo Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
- Doo-Man Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- Choon Hee Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea
- Won-Young Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
- Soon Hee Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Korea
- Dong Joon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea
- Sung-Rae Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Changwon Fatima Hospital, Changwon, Korea
- Chang Hee Jung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Hyun Jeong Jeon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
- Seung-Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Keun-Young Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea
- Sang Youl Rhee
- Department of Endocrinology and Metabolism, Kyung Hee University Hospital, College of Medicine, Kyung Hee University, Seoul, Korea
- Sin Gon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
- Seok O Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gwangmyeong Sungae Hospital, Gwangmyeong, Korea
- Dae Jung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
- Byung Joon Kim
- Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
- Sang Ah Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea
- Yong-Hyun Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Korea
- Kyung-Soo Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
- Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
- Il Seong Nam-Goong
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
- Chang Won Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Busan St. Mary’s Hospital, Busan, Korea
- Duk Kyu Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dong-A University Hospital, Dong-A University College of Medicine, Busan, Korea
- Sang Wook Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
- Chung Gu Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Wonkwang University Hospital, Wonkwang University School of Medicine, Iksan, Korea
- Jung Han Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sungae Hospital, Seoul, Korea
- Yeo-Joo Kim
- Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea
- Jae-Myung Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
- Kyung Wan Min
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea
- Moon-Kyu Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu, Korea
- DOI
- https://doi.org/10.4093/dmj.2023.0077
- Journal volume & issue
-
Vol. 48,
no. 4
pp. 730 – 739
Abstract
Background It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and 100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
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