PMID- 33530982 OWN - NLM STAT- MEDLINE DCOM- 20211005 LR - 20221207 IS - 1475-2840 (Electronic) IS - 1475-2840 (Linking) VI - 20 IP - 1 DP - 2021 Feb 2 TI - A prospective randomized study comparing effects of empagliflozin to sitagliptin on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes: the ASSET study. PG - 32 LID - 10.1186/s12933-021-01228-3 [doi] LID - 32 AB - BACKGROUND: While the cardioprotective benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors have been established in patients with cardiovascular disease (CVD), their advantages over other anti-diabetic drugs at earlier stages remain unclear. We compared the cardioprotective effects of empagliflozin, an SGLT2 inhibitor, with those of sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, focusing on cardiac fat accumulation, cardiac function, and cardiac metabolism in patients with early-stage type 2 diabetes mellitus (T2DM) without CVD complications. METHODS: This was a prospective, randomized, open-label, blinded-endpoint, parallel-group trial that enrolled 44 Japanese patients with T2DM. The patients were randomized for 12-week administration of empagliflozin or sitagliptin. Pericardial fat accumulation and myocardial triglyceride content were evaluated by magnetic resonance imaging and proton magnetic resonance spectroscopy, respectively. Echocardiography, (123)I-beta-methyl-iodophenyl pentadecanoic acid myocardial scintigraphy, and laboratory tests were performed at baseline and after the 12-week treatment period. RESULTS: The patients were middle-aged (50.3 +/- 10.7 years, mean +/- standard deviation) and overweight (body mass index 29.3 +/- 4.9 kg/m(2)). They had a short diabetes duration (3.5 +/- 3.2 years), HbA1c levels of 7.1 +/- 0.8%, and preserved cardiac function (ejection fraction 73.8 +/- 5.0%) with no vascular complications, except for one baseline case each of diabetic nephropathy and peripheral arterial disease. After the 12-week treatment, no differences from baseline were observed between the two groups regarding changes in pericardial, epicardial, and paracardial fat content; myocardial triglyceride content; cardiac function and mass; and cardiac fatty acid metabolism. However, considering cardiometabolic biomarkers, high-density lipoprotein cholesterol and ketone bodies, including beta-hydroxybutyric acid, were significantly increased, whereas uric acid, plasma glucose, plasma insulin, and homeostasis model assessment of insulin resistance were significantly lower in the empagliflozin group than in the sitagliptin group (p < 0.05). CONCLUSIONS: Although the effects on cardiac fat and function were not statistically different between the two groups, empagliflozin exhibited superior effects on cardiometabolic biomarkers, such as uric acid, high-density lipoprotein cholesterol, ketone bodies, and insulin sensitivity. Therefore, when considering the primary preventive strategies for CVD, early supplementation with SGLT2 inhibitors may be more beneficial than DPP-4 inhibitors, even in patients with early-stage T2DM without current CVD complications. CLINICAL TRIAL REGISTRATION: UMIN000026340; registered on February 28, 2017. https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000030257. FAU - Hiruma, Shigenori AU - Hiruma S AD - Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Shigiyama, Fumika AU - Shigiyama F AD - Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Hisatake, Shinji AU - Hisatake S AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Mizumura, Sunao AU - Mizumura S AD - Department of Radiology, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Shiraga, Nobuyuki AU - Shiraga N AD - Department of Radiology, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Hori, Masaaki AU - Hori M AD - Department of Radiology, Toho University Omori Medical Center, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Ikeda, Takanori AU - Ikeda T AD - Division of Cardiovascular Medicine, Department of Internal Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Hirose, Takahisa AU - Hirose T AD - Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. FAU - Kumashiro, Naoki AU - Kumashiro N AUID- ORCID: 0000-0002-5432-3599 AD - Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University Graduate School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, Japan. naoki.kumashiro@med.toho-u.ac.jp. LA - eng SI - UMIN-CTR/UMIN000026340 PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20210202 PL - England TA - Cardiovasc Diabetol JT - Cardiovascular diabetology JID - 101147637 RN - 0 (Benzhydryl Compounds) RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Dipeptidyl-Peptidase IV Inhibitors) RN - 0 (Glucosides) RN - 0 (Glycated Hemoglobin A) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (hemoglobin A1c protein, human) RN - HDC1R2M35U (empagliflozin) RN - TS63EW8X6F (Sitagliptin Phosphate) SB - IM MH - Adiposity/*drug effects MH - Adult MH - Benzhydryl Compounds/adverse effects/*therapeutic use MH - Biomarkers/blood MH - Blood Glucose/drug effects/metabolism MH - Cardiovascular Diseases/diagnosis/metabolism/physiopathology/*prevention & control MH - Diabetes Mellitus, Type 2/diagnosis/*drug therapy/metabolism/physiopathology MH - Dipeptidyl-Peptidase IV Inhibitors/adverse effects/*therapeutic use MH - Energy Metabolism/*drug effects MH - Female MH - Glucosides/adverse effects/*therapeutic use MH - Glycated Hemoglobin/metabolism MH - Heart/*drug effects/physiopathology MH - Humans MH - Male MH - Middle Aged MH - Myocardium/*metabolism MH - Primary Prevention MH - Prospective Studies MH - Sitagliptin Phosphate/adverse effects/*therapeutic use MH - Sodium-Glucose Transporter 2 Inhibitors/adverse effects/*therapeutic use MH - Time Factors MH - Tokyo MH - Treatment Outcome PMC - PMC7852076 OTO - NOTNLM OT - 123I-BMIPP scintigraphy OT - DPP-4 inhibitor OT - Early-stage type 2 diabetes mellitus OT - Epicardial fat OT - Myocardial triglyceride content OT - Pericardial fat OT - Preserved cardiac function OT - SGLT2 inhibitor COIS- NK received research funds from Nippon Boehringer Ingelheim Co., Ltd., and lecture fees from Takeda Pharmaceutical Company Ltd.; Ono Pharmaceutical Co., Ltd.; Mitsubishi Tanabe Pharma Corporation; and Nippon Boehringer Ingelheim Co., Ltd. TH received research funds from AstraZeneca K.K., Mitsubishi Tanabe Pharma Corporation, and Novo Nordisk Pharma Ltd., and lecture fees from Sanofi K.K.; Eli Lilly Japan K.K.; Novo Nordisk Pharma Ltd.; Sumitomo Dainippon Pharma Co., Ltd.; Ono Pharmaceutical Co., Ltd.; AstraZeneca K.K.; Mitsubishi Tanabe Pharma Corporation; and Kowa Company, Limited. All funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. SH1, FS, SH2, SM, NS, MH, and TI declare that they have no conflicts of interest. EDAT- 2021/02/04 06:00 MHDA- 2021/10/06 06:00 PMCR- 2021/02/02 CRDT- 2021/02/03 05:36 PHST- 2020/12/09 00:00 [received] PHST- 2021/01/25 00:00 [accepted] PHST- 2021/02/03 05:36 [entrez] PHST- 2021/02/04 06:00 [pubmed] PHST- 2021/10/06 06:00 [medline] PHST- 2021/02/02 00:00 [pmc-release] AID - 10.1186/s12933-021-01228-3 [pii] AID - 1228 [pii] AID - 10.1186/s12933-021-01228-3 [doi] PST - epublish SO - Cardiovasc Diabetol. 2021 Feb 2;20(1):32. doi: 10.1186/s12933-021-01228-3.