Endocrinology and Metabolism

Original Article

Diabetes, obesity and metabolism
Discrepancies in Dapagliflozin Response in Terms of Glycemic Control and Body Weight Reduction: Ji Eun Jun, Kyoung-Ah Kim, Nan-Hee Kim, Kwan-Woo Lee, In-Kyung Jeong, on Behalf of the BEYOND Investigators; Endocrinol Metab. 2025;40(2):278-288. Published online March 19, 2025; DOI: https://doi.org/10.3803/EnM.2024.2142

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Abstract PDF Supplementary Material PubReader ePub: Background
Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia and obesity by inhibiting renal glucose reabsorption. This post hoc study evaluated clinical factors influencing patient response to dapagliflozin.
Methods
The analysis focused on patients treated with dapagliflozin (10 mg/day for 52 weeks) within the randomized, double-blind, parallel-group BEYOND trial. Adequate glycemic control (GC) was defined as a reduction in glycated hemoglobin (HbA1c) of ≥ 1.0% or the achievement of an HbA1c level <7.0% at week 52. Significant weight loss (WL) referred to a reduction in body weight of ≥3.0% at week 52. Participants were classified into four groups based on their GC and WL responses: GC+/WL+, GC+/WL−, GC−/WL+, and GC−/WL−.
Results
Among dapagliflozin recipients (n=56), at 52 weeks, HbA1c had decreased by 1.0%±0.8% from baseline, while body weight had declined by 2.4±3.1 kg. Overall, 69.6% of participants achieved GC+, and 57.1% achieved WL+. Male sex and shorter diabetes duration were significantly associated with achieving GC+. Conversely, higher estimated glomerular filtration rate was significantly linked to WL+. The only factor significantly associated with both GC+ and WL+ was shorter diabetes duration (odds ratio, 0.81; 95% confidence interval, 0.68 to 0.97; P=0.023). The GC+ and WL+ groups exhibited favorable responses beginning soon after dapagliflozin therapy was initiated. Furthermore, HbA1c decline was more strongly associated with reduction in visceral fat than with WL.
Conclusion
A short duration of diabetes and early response to treatment appear to represent key factors in maximizing the benefits of dapagliflozin for blood glucose and weight management.

Review Article

Diabetes, obesity and metabolism
Brown Fat and Metabolic Health: The Diverse Functions of Dietary Components: Zachary Brown, Takeshi Yoneshiro; Endocrinol Metab. 2024;39(6):839-846. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2121

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Abstract PDF PubReader ePub: Brown and beige adipocytes utilize a variety of substrates for cold-induced thermogenesis, contributing to the clearance of metabolites in circulation and, consequently, metabolic health. Food-derived compounds that exhibit agonistic activity at temperature-sensitive transient receptor potential channels may serve as cold mimics to elicit thermogenesis and substrate utilization in brown adipose tissue (BAT). In addition to fatty acids and glucose, branched-chain amino acids (BCAAs), which are essential amino acids obtained from foods, are actively catabolized in BAT through mitochondrial BCAA carrier (MBC). The relative contribution of BCAAs to fueling the tricarboxylic acid cycle as a substrate (i.e., anaplerosis) is estimated to be relatively small, yet BCAA catabolism in BAT exerts a critical role in systemic insulin sensitivity. The nature of this apparent tension remained unclear until the recent discovery that active BCAA catabolism in BAT through MBC is critical for the synthesis of metabolites such as glutathione, which is delivered to the liver to improve hepatic insulin sensitivity through redox homeostasis. Novel mechanistic insights into the control of BAT function and systemic metabolism reveal the therapeutic potential of food-derived compounds for improving metabolic flexibility and insulin sensitivity.

Brief Report

Diabetes, obesity and metabolism
Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment: Hyun Ah Kim, Han Na Jang, Sung Hye Kong, Young Lee, Sung Hee Choi, Young Min Cho, Hak Chul Jang, Tae Jung Oh; Endocrinol Metab. 2024;39(4):653-658. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1919

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We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, –0.02 mL/min/1.73 m² [95% confidence interval (CI), –3.87 to 3.83 mL/min/1.73 m²] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m² [95% CI, 3.16 to 10.46 mL/min/1.73 m²]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications’ substantial renoprotective effects in individuals with ketonuria.

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Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression
Melina Messing, Jacob A. Torres, Nickolas Holznecht, Thomas Weimbs
Nutrients.2024; 16(19): 3281. CrossRef

Original Articles

Diabetes, obesity and metabolism
Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway: Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee; Endocrinol Metab. 2024;39(1):98-108. Published online January 3, 2024; DOI: https://doi.org/10.3803/EnM.2023.1786

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Background
Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states.
Methods
Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco’s modified Eagle’s medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours.
Results
SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation.
Conclusion
These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Citations

Citations to this article as recorded by

Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes
Dong Hee Kim, Min Jin Lee, Dasol Kang, Ah Reum Khang, Ji Hyun Bae, Joo Yeon Kim, Su Hyun Kim, Yang Ho Kang, Dongwon Yi
Current Issues in Molecular Biology.2024; 46(7): 7505. CrossRef
Sodium-glucose cotransporter 2 inhibitors ameliorate ER stress-induced pro-inflammatory cytokine expression by inhibiting CD36 in NAFLD progression in vitro
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Yu-Mi Lim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Biochemical and Biophysical Research Communications.2024; 735: 150620. CrossRef

Diabetes, obesity and metabolism
Efficacy of Gemigliptin Add-on to Dapagliflozin and Metformin in Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Study (SOLUTION): Byung Wan Lee, KyungWan Min, Eun-Gyoung Hong, Bon Jeong Ku, Jun Goo Kang, Suk Chon, Won-Young Lee, Mi Kyoung Park, Jae Hyeon Kim, Sang Yong Kim, Keeho Song, Soon Jib Yoo; Endocrinol Metab. 2023;38(3):328-337. Published online June 28, 2023; DOI: https://doi.org/10.3803/EnM.2023.1688

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Background
This study evaluated the efficacy and safety of add-on gemigliptin in patients with type 2 diabetes mellitus (T2DM) who had inadequate glycemic control with metformin and dapagliflozin.
Methods
In this randomized, placebo-controlled, parallel-group, double-blind, phase III study, 315 patients were randomized to receive either gemigliptin 50 mg (n=159) or placebo (n=156) with metformin and dapagliflozin for 24 weeks. After the 24-week treatment, patients who received the placebo were switched to gemigliptin, and all patients were treated with gemigliptin for an additional 28 weeks.
Results
The baseline characteristics were similar between the two groups, except for body mass index. At week 24, the least squares mean difference (standard error) in hemoglobin A1c (HbA1c) changes was –0.66% (0.07) with a 95% confidence interval of –0.80% to –0.52%, demonstrating superior HbA1c reduction in the gemigliptin group. After week 24, the HbA1c level significantly decreased in the placebo group as gemigliptin was administered, whereas the efficacy of HbA1c reduction was maintained up to week 52 in the gemigliptin group. The safety profiles were similar: the incidence rates of treatment-emergent adverse events up to week 24 were 27.67% and 29.22% in the gemigliptin and placebo groups, respectively. The safety profiles after week 24 were similar to those up to week 24 in both groups, and no new safety findings, including hypoglycemia, were noted.
Conclusion
Add-on gemigliptin was well tolerated, providing comparable safety profiles and superior efficacy in glycemic control over placebo for long-term use in patients with T2DM who had poor glycemic control with metformin and dapagliflozin.

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Dual add‐on therapy of gemigliptin and dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin alone: The SOLUTION 2 study
Kyung Ah Han, You‐Cheol Hwang, Shin Je Moon, Ho Chan Cho, Hye Jin Yoo, Sung Hee Choi, Suk Chon, Kyoung‐Ah Kim, Tae Nyun Kim, Jun Goo Kang, Cheol‐Young Park, Jong Chul Won, Eunjoo Cho, Jeongyun Kim, Kyong Soo Park
Diabetes, Obesity and Metabolism.2024; 26(9): 3743. CrossRef

Bone Metabolism
Comparison of the Effects of Various Antidiabetic Medication on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: Jeonghoon Ha, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Seung Hyun Ko, Moo Il Kang, Sung Dae Moon, Ki-Hyun Baek; Endocrinol Metab. 2021;36(4):895-903. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1026

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Background
Prospective comparative studies on the effects of various antidiabetic agents on bone metabolism are limited. This study aimed to assess changes in bone mass and biochemical bone markers in postmenopausal patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective, multicenter, open-label, comparative trial included 264 patients with T2DM. Patients who had received a metformin, or sulfonylurea/metformin combination (Group 1); a thiazolidinedione combination (Group 2); a dipeptidyl peptidase-4 inhibitor (gemigliptin) combination (Group 3); or an sodium-glucose cotransporter 2 inhibitor (empagliflozin) combination (Group 4) were prospectively treated for 12 months; bone mineral density (BMD) and bone turnover marker (BTM) changes were evaluated.
Results
The femoral neck BMD percentage changes were −0.79%±2.86% (Group 1), −2.50%±3.08% (Group 2), −1.05%±2.74% (Group 3), and −1.24%±2.91% (Group 4) (P<0.05). The total hip BMD percentage changes were −0.57%±1.79% (Group 1), −1.74%±1.48% (Group 2), −0.75%±1.87% (Group 3), and −1.27%±1.72% (Group 4) (P<0.05). Mean serum BTM (C-terminal type 1 collagen telopeptide and procollagen type 1 amino-terminal propeptide) levels measured during the study period did not change over time or differ between groups.
Conclusion
Significant bone loss in the femoral neck and total hip was associated with thiazolidinedione combination regimens. However, bone loss was not significantly associated with combination regimens including gemigliptin or empagliflozin. Caution should be exercised during treatment with antidiabetic medications that adversely affect the bone in patients with diabetes at a high risk of bone loss.

Citations

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Dapagliflozin Improves High‐Fat Diet‐Induced Cognitive Impairment in Female Mice
Xiaolin Chen, Mingxia Fan, Zhuoni Xiao, Xiaoxing Xiong
Brain and Behavior.2025;[Epub] CrossRef
Meta-Analysis on the Association Between DPP-4 Inhibitors and Bone Mineral Density and Osteoporosis
Lili Huang, Wei Zhong, Xinghuan Liang, Huijuan Wang, Shi-en Fu, Zuojie Luo
Journal of Clinical Densitometry.2024; 27(1): 101455. CrossRef
A multicentre, double‐blind, placebo‐controlled, randomized, parallel comparison, phase 3 trial to evaluate the efficacy and safety of pioglitazone add‐on therapy in type 2 diabetic patients treated with metformin and dapagliflozin
Soo Lim, Seung‐Hwan Lee, Kyung‐Wan Min, Chang Beom Lee, Sang Yong Kim, Hye Jin Yoo, Nan Hee Kim, Jae Hyeon Kim, Seungjoon Oh, Jong Chul Won, Hyuk Sang Kwon, Mi Kyung Kim, Jung Hwan Park, In‐Kyung Jeong, Sungrae Kim
Diabetes, Obesity and Metabolism.2024; 26(6): 2188. CrossRef
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Krisztina Kupai, Hsu Lin Kang, Anikó Pósa, Ákos Csonka, Tamás Várkonyi, Zsuzsanna Valkusz
International Journal of Molecular Sciences.2024; 25(13): 7269. CrossRef
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L. M. Pechmann, F. I. Pinheiro, V. F. C. Andrade, C. A. Moreira
Diabetology & Metabolic Syndrome.2024;[Epub] CrossRef
The effect of antidiabetic drugs on bone metabolism: a concise review
Stavroula Psachna, Maria Eleni Chondrogianni, Konstantinos Stathopoulos, Antonis Polymeris, Antonios Chatzigeorgiou, Efstathios Chronopoulos, Symeon Tournis, Eva Kassi
Endocrine.2024; 87(3): 907. CrossRef
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Yilin Hou, Xiaoyu Hou, Qian Nie, Qiuyang Xia, Rui Hu, Xiaoyue Yang, Guangyao Song, Luping Ren
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1177. CrossRef
Complementary effects of dapagliflozin and lobeglitazone on metabolism in a diet-induced obese mouse model
Yun Kyung Lee, Tae Jung Oh, Ji In Lee, Bo Yoon Choi, Hyen Chung Cho, Hak Chul Jang, Sung Hee Choi
European Journal of Pharmacology.2023; 957: 175946. CrossRef

Review Article

Diabetes
Cardiorenal Protection in Diabetic Kidney Disease: Jason F. Lee, Ecaterina Berzan, Vikas S. Sridhar, Ayodele Odutayo, David Z.I. Cherney; Endocrinol Metab. 2021;36(2):256-269. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2021.987

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Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.

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The Role of GLP-1 Receptor Agonists in Diabetic Kidney Disease: Recent Evidence
Jin Hwa Kim
The Journal of Korean Diabetes.2025; 26(1): 5. CrossRef
Expert Opinion on Fixed Dose Combination of Dapagliflozin Plus Sitagliptin for Unmet Cardiovascular Benefits in Type 2 Diabetes Mellitus
Soumitra Ray, J Ezhilan, Rajiv Karnik, Ashish Prasad, Rajashree Dhar
Journal of Diabetology.2024; 15(2): 131. CrossRef
The significance of finerenone as a novel therapeutic option in diabetic kidney disease: a scoping review with emphasis on cardiorenal outcomes of the finerenone phase 3 trials
Mustafa Arici, Bulent Altun, Mustafa Araz, Aysegul Atmaca, Tevfik Demir, Tevfik Ecder, Galip Guz, Dilek Gogas Yavuz, Alaattin Yildiz, Temel Yilmaz
Frontiers in Medicine.2024;[Epub] CrossRef
Relative and Absolute Risks of Adverse Events with Real-World Use of SGLT2 Inhibitors in CKD
Ayodele Odutayo, Adeera Levin
Clinical Journal of the American Society of Nephrology.2023;[Epub] CrossRef
Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease
Dong-Lim Kim, Seung-Eun Lee, Nan Hee Kim
Endocrinology and Metabolism.2023; 38(1): 43. CrossRef
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis
Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung
Endocrinology and Metabolism.2023; 38(4): 359. CrossRef
SGLT2 and DPP4 inhibitors improve Alzheimer’s disease–like pathology and cognitive function through distinct mechanisms in a T2D–AD mouse model
A Young Sim, Da Hyun Choi, Jong Youl Kim, Eun Ran Kim, A-ra Goh, Yong-ho Lee, Jong Eun Lee
Biomedicine & Pharmacotherapy.2023; 168: 115755. CrossRef
Narrative review investigating the nephroprotective mechanisms of sodium glucose cotransporter type 2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease
Emma S. Speedtsberg, Martin Tepel
Frontiers in Endocrinology.2023;[Epub] CrossRef
Management of CKD
Nimrit Goraya, Jennifer D. Moran
Nephrology Self-Assessment Program.2022; 21(2): 146. CrossRef
Nonsteroidal mineralocorticoid receptor antagonism for cardiovascular and renal disorders − New perspectives for combination therapy
Peter Kolkhof, Amer Joseph, Ulrich Kintscher
Pharmacological Research.2021; 172: 105859. CrossRef
Sodium‐Glucose Cotransporter 2 Inhibitors, All‐Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta‐Analysis and Meta‐Regression
Ayodele Odutayo, Bruno R. da Costa, Tiago V. Pereira, Vinay Garg, Samir Iskander, Fatimah Roble, Rahim Lalji, Cesar A. Hincapié, Aquila Akingbade, Myanca Rodrigues, Arnav Agarwal, Bishoy Lawendy, Pakeezah Saadat, Jacob A. Udell, Francesco Cosentino, Peter
Journal of the American Heart Association.2021;[Epub] CrossRef
Finerenone: A Potential Treatment for Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus
Luis D’Marco, María Jesús Puchades, Lorena Gandía, Claudia Forquet, Elena Giménez-Civera, Nayara Panizo, Javier Reque, Isabel Juan-García, Valmore Bermúdez, José Luis Gorriz
touchREVIEWS in Endocrinology.2021; 17(2): 84. CrossRef
Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review
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Frontiers in Medicine.2021;[Epub] CrossRef

Original Article

Clinical Study
Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis: Jae Hyun Bae, Eun-Gee Park, Sunhee Kim, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim; Endocrinol Metab. 2021;36(2):388-400. Published online March 31, 2021; DOI: https://doi.org/10.3803/EnM.2020.912

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Background
To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes.
Methods
We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes.
Results
Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors.
Conclusion
SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.

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Die Diabetologie.2024; 20(2): 212. CrossRef
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Mototsugu Nagao, Jun Sasaki, Kyoko Tanimura-Inagaki, Ichiro Sakuma, Hitoshi Sugihara, Shinichi Oikawa
Cardiovascular Diabetology.2024;[Epub] CrossRef
Comparative Effect of Glucose-Lowering Drugs for Type 2 Diabetes Mellitus on Stroke Prevention: A Systematic Review and Network Meta-Analysis
Ji Soo Kim, Gyeongsil Lee, Kyung-Il Park, Seung-Won Oh
Diabetes & Metabolism Journal.2024; 48(2): 312. CrossRef
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Clinical Management of Type II DM in patients Showing Progressive Increase in the Creatinine Level – A Cross-sectional Study
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Research Journal of Pharmacy and Technology.2024; : 2719. CrossRef
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Die Diabetologie.2023; 19(5): 658. CrossRef
Renoprotective Effect of Thai Patients with Type 2 Diabetes Mellitus Treated with SGLT-2 Inhibitors versus DPP-4 Inhibitors: A Real-World Observational Study
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Die Diabetologie.2022; 18(5): 623. CrossRef
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Review Article

Diabetes
Best Achievements in Clinical Medicine in Diabetes and Dyslipidemia in 2020: Eun-Jung Rhee, Mee-Kyung Kim, Won-Young Lee; Endocrinol Metab. 2021;36(1):41-50. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.106

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Over the last two decades, our understanding of diabetes and treatment strategies have evolved tremendously, from scientific, mechanistic, and human perspectives. The categories of anti-diabetic medications expanded from a few to numerous, enabling clinicians to personalize diabetes care and treatment. Thanks to rapid growth in the field of science and medical engineering, newer treatment options are coming to the market with various advantages and disadvantages to be aware of. Therefore, clinicians should rapidly adopt new trends based on guidelines and data from many clinical trials in the field of diabetes. In the treatment of dyslipidemia, trends and guidelines are changing every year, and novel therapies are being developed. In this review, we would like to summarize the major achievements in clinical medicine in 2020 in the field of diabetes mellitus and dyslipidemia.

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Original Article

Clinical Study
Glycemic Efficacy and Metabolic Consequences of an Empagliflozin Add-on versus Conventional Dose-Increasing Strategy in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea: Yujin Shin, Ji Hye Moon, Ho Jun Chin, Ele Ferrannini, Soo Lim; Endocrinol Metab. 2020;35(2):329-338. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.329

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Background
We assessed the glucose-lowering efficacy of adding empagliflozin versus dose escalating existing medications in patients with uncontrolled type 2 diabetes (T2D).
Methods
This was a 6-month retrospective case-control study in subjects with uncontrolled T2D (glycated hemoglobin [HbA1c] >7%) on conventional treatment. The study group started add-on therapy with empagliflozin (10 mg once a day) while the control group was up-titrated with existing medication, using either monotherapy or a combination of metformin, sulfonylurea, and a dipeptidyl peptidase-4 inhibitor. The primary endpoints included changes in HbA1c, fasting plasma glucose (FPG), and 2-hour postprandial glucose (PP2) levels. Secondary outcomes included changes in body composition, body mass index (BMI), and serum ketone bodies, and urinary excretion of sodium, potassium, chlorine, calcium, phosphorus, and glucose.
Results
After treatment, the reduction in HbA1c was significantly greater in the empagliflozin group than in controls (from 8.6%±1.6% to 7.6%±1.5% vs. 8.5%±1.1% to 8.1%±1.1%; P<0.01). Similar patterns were found in FPG and PP2 levels. Empagliflozin decreased systolic and diastolic blood pressure, triglycerides, and alanine and aspartate aminotransferase levels. Body weight, BMI, waist circumference, fat mass, and abdominal visceral fat area decreased significantly while lean body mass was maintained. Total ketones, β-hydroxybutyrate, and acetoacetate levels increased significantly after empagliflozin.
Conclusion
In addition to glucose lowering, an empagliflozin add-on regimen decreased blood pressure and body fat, and improved metabolic profiles significantly. Empagliflozin add-on is superior to dose escalation in patients with T2D who have inadequate glycemic control on standard medications.

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Amino Acid Transporters as Potential Therapeutic Targets in Thyroid Cancer: Keisuke Enomoto, Muneki Hotomi; Endocrinol Metab. 2020;35(2):227-236. Published online June 24, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.2.227

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Thyroid cancer cells have a high amino acid demand for proliferation, invasion, and metastasis. Amino acids are taken up by thyroid cancer cells, both thyroid follicular cell and thyroid parafollicular cells (commonly called “C-cells”), via amino acid transporters. Amino acid transporters up-regulate in many cancers, and their expression level associate with clinical aggressiveness and prognosis. This is the review to discuss the therapeutic potential of amino acid transporters and as molecular targets in thyroid cancer.

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A Review of the Effects of Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors on Lean Body Mass in Humans: Jack Alistair Sargeant, Joseph Henson, James Adam King, Thomas Yates, Kamlesh Khunti, Melanie Jane Davies; Endocrinol Metab. 2019;34(3):247-262. Published online September 26, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.3.247

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Weight loss is an important goal in the management of several chronic conditions, including type 2 diabetes mellitus, and pharmacological therapies that aid weight loss are appealing. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are novel glucose-lowering therapies that have been shown to induce clinically significant reductions in body weight. However, this weight loss may not be attributed solely to fat mass (FM). Given the importance of skeletal muscle and lean body mass (LBM) on cardio-metabolic health and physical function, we reviewed the available literature reporting the effects of GLP-1RAs and SGLT2is on body composition. Results demonstrate that, in most circumstances, the weight loss associated with both therapies predominantly comprises a reduction in FM, although significant heterogeneity exists between studies. In over half of the studies identified, the proportion of LBM reduction ranged between 20% and 50% of total weight lost, which is consistent with diet-induced weight loss and bariatric surgery. No clear differences existed between GLP-1RAs and SGLT2is. Consequently, the loss of LBM and skeletal muscle associated with weight loss induced by GLP-1RAs and SGLT2is warrants attention. Strategies to preserve skeletal muscle and improve physical function, for example through structured exercise, are of great importance.

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Original Article

Clinical Study
Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease: Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Bo-Yeon Kim; Endocrinol Metab. 2018;33(3):387-394. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.387

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Abstract PDF PubReader ePub

Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin.

Methods

Among patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed.

Results

A total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (−2.9 kg vs. −0.4 kg, P=0.005; −21.1 U/L vs. −9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046).

Conclusion

ALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Citations

Citations to this article as recorded by

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