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A Comparison of Effects of DPP-4 Inhibitor and SGLT2 Inhibitor On Cha et al. Lipids in Health and Disease (2017) 16:58 DOI 10.1186/s12944-017-0443-4 RESEARCH Open Access A comparison of effects of DPP-4 inhibitor and SGLT2 inhibitor on lipid profile in patients with type 2 diabetes Seon-Ah Cha1, Yong-Moon Park2, Jae-Seung Yun1, Tae-Seok Lim1, Ki-Ho Song1, Ki-Dong Yoo3, Yu-Bae Ahn1 and Seung-Hyun Ko1* Abstract Background: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. Methods: From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled. We compared the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile at baseline and after 24 weeks of treatment. To compare lipid parameters between the two groups, we used the analysis of covariance (ANCOVA). Results: A total of 184 patients completed follow-up (mean age: 53.1 ± 6.9 years, mean duration of diabetes: 7.1 ± 5. 7 years). From baseline to 24 weeks, HDL-cholesterol (HDL-C) levels were increased by 0.5 (95% CI, −0.9 to 2.0) mg/dl with a DPP-4 inhibitor and by 5.1 (95% CI, 3.0 to 7.1) mg/dl with an SGLT2 inhibitor (p = 0.001). LDL-cholesterol (LDL-C) levels were reduced by 8.4 (95% CI, −14.0 to -2.8) mg/dl with a DPP-4 inhibitor, but increased by 1.3 (95% CI, −5.1 to 7.6) mg/dl with an SGLT2 inhibitor (p = 0.046). There was no significant difference in the mean hemoglobin A1c (8.3 ± 1.1 vs. 8.0 ± 0. 9%, p = 0.110) and in the change of total cholesterol (TC) (p = 0.836), triglyceride (TG) (p = 0.867), apolipoprotein A (p =0. 726), apolipoprotein B (p =0.660),andlipoprotein(a)(p = 0.991) between the DPP-4 inhibitor and the SGLT2 inhibitor. Conclusions: The SGLT2 inhibitor was associated with a significant increase in HDL-C and LDL-C after 24 weeks of SGLT2 inhibitor treatment in patients with type 2 diabetes compared with those with DPP-4 inhibitor treatment in this study. Trial registration: This study was conducted by retrospective medical record review. Keywords: DPP-4 inhibitor, SGLT2 inhibitor, Lipid, Type 2 diabetes Background has average annual per-person medical care costs Diabetes mellitus is related to an increased risk of car- adjusted for age and sex that are 1.6-fold higher than diovascular disease (CVD) [1]. In Korea, a risk of coron- those without diabetes [6]. ary heart disease and stroke were 4 times and 2 times Contributing factors that increase the risk of CVD higher in patients with diabetes compared with those include hypertension, dyslipidemia, obesity, and smoking in without diabetes, respectively [2]. CVD is the major patients with diabetes [4]. Dyslipidemia is common in cause of morbidity and cardiovascular mortality in patients with type 2 diabetes, which is characterized by low patients with type 2 diabetes [3–5]. Diabetes with CVD HDL-cholesterol (HDL-C), elevated triglycerides (TG), and a predominance of small, dense LDL particles [7, 8]. The American Diabetes Association (ADA) and * Correspondence: [email protected] American College of Cardiology Foundation recommend 1Department of Internal Medicine, Division of Endocrinology and Metabolism, College of Medicine, The Catholic University of Korea, St. that lifestyle intervention and pharmacologic therapy be Vincent’s Hospital, 93 Jungbu − daero, Paldal − gu, Suwon, Gyeonggi − do, started concurrently in patients with type 2 diabetes, Seoul 442-723, Republic of Korea regardless of LDL-cholesterol (LDL-C) [9]. In its recent Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Cha et al. Lipids in Health and Disease (2017) 16:58 Page 2 of 8 guideline, the ADA recommended pharmacologic thyroid hormones, steroids within 3 months before therapy, primarily statin therapy, in patients with type 2 enrollment or during the period of DPP-4 inhibitor or diabetes who have any CVD risk factors or patients SGLT2 inhibitor treatment, fasting serum TG ≥ 600 mg/dl 40 years of age or older [10]. at screening, or estimated glomerular filtration rate (eGFR) Despite the evidence that lowered LDL-C could lead to less than 60 ml/min/1.73 m2. The enrolled patients were reduced risk of CVD, it is estimated that nearly half of pa- divided into two groups (DPP-4 inhibitor group or SGLT2 tients with type 2 diabetes did not achieve current LDL-C inhibitor group) according to the drugs that they were re- goals [11, 12]. Thus, a relatively large number of patients ceiving. This study was conducted in accordance with the with type 2 diabetes are exposed to the risks of CVD [13]. Declaration of Helsinki guidelines, and it was approved by A dipeptidyl peptidase-4 (DPP-4) inhibitor is an oral investigator’s institutional ethical review board. hypoglycemic agent that exerts its effect by inactivating Information including participant’s history, ex- or current incretin, which is released from the intestinal cells after cigarette smoking status, and use of medication were meal ingestion [11]. In Korea, the use of DPP-4 inhibitors collected at the beginning of the study. Hypertension was has increased in the last decade, and DPP-4 inhibitors defined as systolic blood pressure of 140 mmHg or greater, comprised one-third of the market share in 2013 [14]. Pre- diastolic blood pressure of 90 mmHg or greater, or current vious studies reported that DPP-4 inhibitors have effects on use of antihypertensive medications. total cholesterol (TC), but results are variable across trials. The fasting blood samples, including the levels of fasting A recent meta-analysis reported a possible beneficial effect plasma glucose (FPG), hemoglobin A1c (HbA1c), TC, TG, of DPP-4 inhibitors including vildagliptin and alogliptin on HDL-C, LDL-C, lipoprotein (a) (Lp[a]), apolipoprotein A, TC and TG levels compared to placebo [15]. apolipoprotein B and creatinine, aspartate aminotransferase, A sodium glucose cotransporter 2 (SGLT2) inhibitor is and alanine transaminase, were measured at baseline and an antihyperglycemic agent that effectively improves gly- 24 weeks after DPP-4 inhibitor or SGLT2 inhibitor therapy. cemic control through inhibiting glucose absorption in the The FPG and lipid profile were assessed using an auto- proximal tubule of the kidney [16]. In addition to improv- mated enzymatic method (736–40; Hitachi, Tokyo, Japan), ing glycemic control, SGLT2 inhibitors are reported to have and HbA1c was assessed using high-performance liquid additional beneficial effects on body weight and blood chromatography (Bio-Rad, Montreal, QC, Canada). Serum pressure, with a low risk of hypoglycemia. SGLT2 inhibitors Lp(a) concentration was measured using a one-step sand- are also reported to have an association with increases in wich enzyme-linked immunoassay (TintElize Lp(a) kt, HDL-C and LDL-C [17]. The mechanism that an SGLT2 Biopool AB, Umea, Sweden) [19]. The eGFR was assessed inhibitor increases LDL-C levels remains unknown, and a using the four-component Modification of Diet in Renal dose-related increase in LDL-C has been observed in Disease equation [20]. The urinary albumin excretion patients who were given an SGLT2 inhibitor [18]. rates were measured from single-void urine specimens DPP-4 inhibitors and SGLT2 inhibitors are both a using immunoturbidimetry (Eiken, Tokyo, Japan). C- treatment option as monotherapy or as part of dual and peptide and insulin levels were measured using a chemilu- triple therapy in patients with type 2 diabetes, having minescent microparticle immunoassay (ARCHITECT C- different effects on the lipid profile. This study com- Peptide Reagent Kit [CL53], Biokit S.A., Barcelona, Spain, pared the effects of two DPP-4 inhibitors (linagliptin, ARCHITECT Insulin, Denka Seiken Co., Ltd. Tokyo, gemigliptin) and an SGLT2 inhibitor (dapagliflozin) on Japan). Insulin resistance and insulin secretion were esti- the lipid profile in patients with type 2 diabetes. mated by homeostatic model assessment-insulin resist- ance (HOMA-IR) and the HOMA β-Cell function. Methods Diabetic retinopathy was assessed through a compre- Through retrospective medical record review, a total of hensive eye examination by an ophthalmologist from 228 patients with type 2 diabetes, aged 25–65 years and retinal photographs taken at baseline. Diabetic nephrop- who did not achieve glycemic goals with metformin and/ athy was defined as a urine albumin-to-creatinine ratio > or a sulfonylurea and were receiving linagliptin or gemi- 30 mg/g of creatinine in spot urine specimens [21]. gliptin or dapagliflozin as add-on therapy, were consecu- tively recruited from January 2013 to December 2015, Statistical analysis and scheduled for follow-up from July 2013 to June 2016 All data are expressed as the mean ± standard deviation at the university-affiliated diabetes center of St. Vincent’s or frequencies or medians with an interquartile range or Hospital in South Korea.
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