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Original Articles
- Drug/Regimen
- Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
- Ji-Yeon Park, Joonyub Lee, Yoon-Hee Choi, Kyung Wan Min, Kyung Ah Han, Kyu Jeung Ahn, Soo Lim, Young-Hyun Kim, Chul Woo Ahn, Kyung Mook Choi, Kun-Ho Yoon, the Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) study investigators
- Received August 7, 2023 Accepted November 30, 2023 Published online April 23, 2024
- DOI: https://doi.org/10.4093/dmj.2023.0259 [Epub ahead of print]
- 196 View
- 8 Download
-
Abstract
PDF - Background
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.
- Drug Regimen
- Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension
- Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon
- Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023
- DOI: https://doi.org/10.4093/dmj.2022.0387
- 2,576 View
- 281 Download
-
Abstract
PDF
Supplementary Material
PubReader 
ePub - Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.
Sulwon Lecture 2022
- Others
- Opening the Precision Diabetes Care through Digital Healthcare
- Joonyub Lee, Jin Yu, Kun-Ho Yoon
- Diabetes Metab J. 2023;47(3):307-314. Published online March 29, 2023
- DOI: https://doi.org/10.4093/dmj.2022.0386
- 5,263 View
- 247 Download
-
Abstract
PDFPubReader ePub
- The national healthcare systems of every country in the world cannot sustain the rise in healthcare expenditure caused by chronic diseases and their complications. To sustain the national healthcare system, a novel system should be developed to improve the quality of care and minimize healthcare costs. For 20 years, our team developed patient-communicating digital healthcare platforms and proved their efficacy. National scale randomized control trials are underway to systematically measure the efficacy and economic benefits of this digital health care system. Precision medicine aims to maximize effectiveness of disease management by considering individual variability. Digital health technologies enable precision medicine at a reasonable cost that was not available before. The government launched the “National Integrated Bio-big Data Project” which will collect diverse health data from the participants. Individuals will share their health information to physicians or researchers at their will by gateway named “My-Healthway.’ Taken together, now we stand in front of the evolution of medical care, so-called “Precision medicine.” led by various kinds of technologies and a huge amount of health information exchange. We should lead these new trends as pioneers, not as followers, to establish and implement the best care for our patients that can help them to withstand their devastating diseases.
Original Article
- Basic Research
- Differentiation of Microencapsulated Neonatal Porcine Pancreatic Cell Clusters in Vitro Improves Transplant Efficacy in Type 1 Diabetes Mellitus Mice
- Gyeong-Jin Cheon, Heon-Seok Park, Eun-Young Lee, Min Jung Kim, Young-Hye You, Marie Rhee, Ji-Won Kim, Kun-Ho Yoon
- Diabetes Metab J. 2022;46(5):677-688. Published online February 7, 2022
- DOI: https://doi.org/10.4093/dmj.2021.0202
- 4,520 View
- 252 Download
- 2 Web of Science
- 2 Crossref
-
Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Neonatal porcine pancreatic cell clusters (NPCCs) have been proposed as an alternative source of β cells for islet transplantation because of their low cost and growth potential after transplantation. However, the delayed glucose lowering effect due to the immaturity of NPCCs and immunologic rejection remain as a barrier to NPCC’s clinical application. Here, we demonstrate accelerated differentiation and immune-tolerant NPCCs by in vitro chemical treatment and microencapsulation.
Methods
NPCCs isolated from 3-day-old piglets were cultured in F-10 media and then microencapsulated with alginate on day 5. Differentiation of NPCCs is facilitated by media supplemented with activin receptor-like kinase 5 inhibitor II, triiodothyronine and exendin-4 for 2 weeks. Marginal number of microencapsulated NPCCs to cure diabetes with and without differentiation were transplanted into diabetic mice and observed for 8 weeks.
Results
The proportion of insulin-positive cells and insulin mRNA levels of NPCCs were significantly increased in vitro in the differentiated group compared with the undifferentiated group. Blood glucose levels decreased eventually after transplantation of microencapsulated NPCCs in diabetic mice and normalized after 7 weeks in the differentiated group. In addition, the differentiated group showed nearly normal glucose tolerance at 8 weeks after transplantation. In contrast, neither blood glucose levels nor glucose tolerance were improved in the undifferentiated group. Retrieved graft in the differentiated group showed greater insulin response to high glucose compared with the undifferentiated group.
Conclusion
in vitro differentiation of microencapsulated immature NPCCs increased the proportion of insulin-positive cells and improved transplant efficacy in diabetic mice without immune rejection. -
Citations
Citations to this article as recorded by
- Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes
Sang Hoon Lee, Minse Kim, Eun-Jin Lee, Sun Mi Ahn, Yu-Rim Ahn, Jaewon Choi, Jung-Taek Kang, Hyun-Ouk Kim
Discover Nano.2024;[Epub] CrossRef - Long‐term efficacy of encapsulated xenogeneic islet transplantation: Impact of encapsulation techniques and donor genetic traits
Heon‐Seok Park, Eun Young Lee, Young‐Hye You, Marie Rhee, Jong‐Min Kim, Seong‐Soo Hwang, Poong‐Yeon Lee
Journal of Diabetes Investigation.2024;[Epub] CrossRef
- Dual-targeted nano-encapsulation of neonatal porcine islet-like cell clusters with triiodothyronine-loaded bifunctional polymersomes
Reviews
- Drug/Regimen
- A Century of Progress in Diabetes Care with Insulin: A History of Innovations and Foundation for the Future
- Seung-Hwan Lee, Kun-Ho Yoon
- Diabetes Metab J. 2021;45(5):629-640. Published online September 30, 2021
- DOI: https://doi.org/10.4093/dmj.2021.0163
- 8,533 View
- 452 Download
- 13 Web of Science
- 15 Crossref
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Graphical Abstract
Abstract
PDFPubReader ePub - The year 2021 marks the 100th anniversary of the discovery of insulin, which has greatly changed the lives of people with diabetes and become a cornerstone of advances in medical science. A rapid bench-to-bedside application of the lifesaving pancreatic extract and its immediate commercialization was the result of a promising idea, positive drive, perseverance, and collaboration of Banting and colleagues. As one of the very few proteins isolated in a pure form at that time, insulin also played a key role in the development of important methodologies and in the beginning of various fields of modern science. Since its discovery, insulin has evolved continuously to optimize the care of people with diabetes. Since the 1980s, recombinant DNA technology has been employed to engineer insulin analogs by modifying their amino acid sequence, which has resulted in the production of insulins with various profiles that are currently used. However, unmet needs in insulin treatment still exist, and several forms of future insulins are under development. In this review, we discuss the past, present, and future of insulin, including a history of ceaseless innovations and collective intelligence. We believe that this story will be a solid foundation and an unerring guide for the future.
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Citations
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- Guideline/Fact Sheet
- 2021 Clinical Practice Guidelines for Diabetes Mellitus in Korea
- Kyu Yeon Hur, Min Kyong Moon, Jong Suk Park, Soo-Kyung Kim, Seung-Hwan Lee, Jae-Seung Yun, Jong Ha Baek, Junghyun Noh, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Ye Seul Yang, Jang Won Son, Jong Han Choi, Kee Ho Song, Nam Hoon Kim, Sang Yong Kim, Jin Wha Kim, Sang Youl Rhee, You-Bin Lee, Sang-Man Jin, Jae Hyeon Kim, Chong Hwa Kim, Dae Jung Kim, SungWan Chun, Eun-Jung Rhee, Hyun Min Kim, Hyun Jung Kim, Donghyun Jee, Jae Hyun Kim, Won Seok Choi, Eun-Young Lee, Kun-Ho Yoon, Seung-Hyun Ko, Committee of Clinical Practice Guidelines, Korean Diabetes Association
- Diabetes Metab J. 2021;45(4):461-481. Published online July 30, 2021
- DOI: https://doi.org/10.4093/dmj.2021.0156
- 23,956 View
- 1,626 Download
- 122 Web of Science
- 141 Crossref
-
Graphical Abstract
Abstract
PDFPubReader ePub
- The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.
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Jin-Sung Yuk, Jung Min Kim
Menopause.2023; 30(5): 497. CrossRef - Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus
Takayoshi Sasako, Toshimasa Yamauchi, Kohjiro Ueki
Diabetes & Metabolism Journal.2023; 47(2): 185. CrossRef - Association between antidiabetic drugs and the incidence of atrial fibrillation in patients with type 2 diabetes: A nationwide cohort study in South Korea
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Diabetes Research and Clinical Practice.2023; 198: 110626. CrossRef - Totally robotic Roux-en-Y gastric bypass in a morbidly obese patient in Korea: a case report
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Diabetes Therapy.2023; 14(5): 823. CrossRef - The association of perfluoroalkyl substances (PFAS) exposure and kidney function in Korean adolescents using data from Korean National Environmental Health Survey (KoNEHS) cycle 4 (2018–2020): a cross-sectional study
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Brief Report
- Metabolic Risk/Epidemiology
- Short-Term Effects of the Internet-Based Korea Diabetes Prevention Study: 6-Month Results of a Community-Based Randomized Controlled Trial
- Jin-Hee Lee, Sun-Young Lim, Seon-Ah Cha, Chan-Jung Han, Ah Reum Jung, Kook-Rye Kim, Kun-Ho Yoon, Seung-Hyun Ko
- Diabetes Metab J. 2021;45(6):960-965. Published online March 17, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0225
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- 151 Download
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Abstract
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- The aims of this study were to determine the short-term effectiveness of an internet-based lifestyle modification (LSM) program in preventing the onset of type 2 diabetes mellitus (T2DM) in prediabetes patients in community settings. A total of 415 subjects who were diagnosed with prediabetes were randomly assigned to the LSM and standard management (SM) groups. After the 6-month intervention, the LSM group had a statistically significant reduction in body weight, body mass index compared to the SM group participants. In the LSM group, blood glucose levels were significantly decreased after intervention and the clinical improvement effect was evident in the group that achieved the target weight loss of 5% or more of the initial weight for 6 months. Internet-based 6-month-intensive LSM programs conducted by public health center personnel are an effective way to provide lifestyle intervention programs and encourage maintenance of healthy behaviors in subjects with a high risk of T2DM in community settings.
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Citations
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- U-shaped association between online information exchange and app usage frequency: a large-scale survey of China ‘s online young and middle-aged people with pre diabetes and diabetes
Response
- Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study (Diabetes Metab J 2020;44:737-46)
- Sun Joon Moon, Eun-Jung Rhee, Won-Young Lee, Kun-Ho Yoon
- Diabetes Metab J. 2020;44(6):942-943. Published online December 23, 2020
- DOI: https://doi.org/10.4093/dmj.2020.0266
- 3,683 View
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- 1 Crossref
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Citations
Citations to this article as recorded by- Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases
Nikolaos Perakakis, Hani Harb, Benjamin G Hale, Zsuzsanna Varga, Charlotte Steenblock, Waldemar Kanczkowski, Vasileia Ismini Alexaki, Barbara Ludwig, Peter Mirtschink, Michele Solimena, Nicole Toepfner, Sebastian Zeissig, Manuel Gado, Irene Alma Abela, Fe
The Lancet Diabetes & Endocrinology.2023; 11(9): 675. CrossRef
- Mechanisms and clinical relevance of the bidirectional relationship of viral infections with metabolic diseases
Original Articles
- COVID-19
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- Independent Impact of Diabetes on the Severity of Coronavirus Disease 2019 in 5,307 Patients in South Korea: A Nationwide Cohort Study
- Sun Joon Moon, Eun-Jung Rhee, Jin-Hyung Jung, Kyung-Do Han, Sung-Rae Kim, Won-Young Lee, Kun-Ho Yoon
- Diabetes Metab J. 2020;44(5):737-746. Published online October 21, 2020
- DOI: https://doi.org/10.4093/dmj.2020.0141
- 10,602 View
- 201 Download
- 24 Web of Science
- 23 Crossref
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Abstract
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- Background
Inconsistent results have been observed regarding the independent effect of diabetes on the severity of coronavirus disease 2019 (COVID-19). We conducted a nationwide population-based cohort study to evaluate the relationship between diabetes and COVID-19 severity in South Korea.
Methods
Patients with laboratory-confirmed COVID-19 aged ≥30 years were enrolled and medical claims data were obtained from the Korean Health Insurance Review and Assessment Service. Hospitalization, oxygen treatment, ventilator application, and mortality were assessed as severity outcomes. Multivariate logistic regression analyses were performed after adjusting for age, sex, and comorbidities.
Results
Of 5,307 COVID-19 patients, the mean age was 56.0±14.4 years, 2,043 (38.5%) were male, and 770 (14.5%) had diabetes. The number of patients who were hospitalized, who received oxygen, who required ventilator support, and who died was 4,986 (94.0%), 884 (16.7%), 121 (2.3%), and 211 (4.0%), respectively. The proportion of patients with diabetes in the abovementioned outcome groups was 14.7%, 28.1%, 41.3%, 44.6%, showing an increasing trend according to outcome severity. In multivariate analyses, diabetes was associated with worse outcomes, with an adjusted odds ratio (aOR) of 1.349 (95% confidence interval [CI], 1.099 to 1.656; P=0.004) for oxygen treatment, an aOR of 1.930 (95% CI, 1.276 to 2.915; P<0.001) for ventilator use, and an aOR of 2.659 (95% CI, 1.896 to 3.729; P<0.001) for mortality.
Conclusion
Diabetes was associated with worse clinical outcomes in Korean patients with COVID-19, independent of other comorbidities. Therefore, patients with diabetes and COVID-19 should be treated with caution. -
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- Drug/Regimen
- Effect of Dapagliflozin as an Add-on Therapy to Insulin on the Glycemic Variability in Subjects with Type 2 Diabetes Mellitus (DIVE): A Multicenter, Placebo-Controlled, Double-Blind, Randomized Study
- Seung-Hwan Lee, Kyung-Wan Min, Byung-Wan Lee, In-Kyung Jeong, Soon-Jib Yoo, Hyuk-Sang Kwon, Yoon-Hee Choi, Kun-Ho Yoon
- Diabetes Metab J. 2021;45(3):339-348. Published online May 28, 2020
- DOI: https://doi.org/10.4093/dmj.2019.0203
- 8,284 View
- 332 Download
- 12 Web of Science
- 15 Crossref
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Graphical Abstract
Abstract
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Background Glycemic variability is associated with the development of diabetic complications and hypoglycemia. However, the effect of sodium-glucose transporter 2 (SGLT2) inhibitors on glycemic variability is controversial. We aimed to examine the effect of dapagliflozin as an add-on therapy to insulin on the glycemic variability assessed using continuous glucose monitoring (CGM) in subjects with type 2 diabetes mellitus.
Methods In this multicenter, placebo-controlled, double-blind, randomized study, 84 subjects received 10 mg of dapagliflozin (
n =41) or the placebo (n =43) for 12 weeks. CGM was performed before and after treatment to compare the changes in glycemic variability measures (standard deviation [SD], mean amplitude of glycemic excursions [MAGEs]).Results At week 12, significant reductions in glycosylated hemoglobin (−0.74%±0.66% vs. 0.01%±0.65%,
P <0.001), glycated albumin (−3.94%±2.55% vs. −0.67%±2.48%,P <0.001), and CGM-derived mean glucose (−41.6±39.2 mg/dL vs. 1.1±46.2 mg/dL,P <0.001) levels were observed in the dapagliflozin group compared with the placebo group. SD and MAGE were significantly decreased in the dapagliflozin group, but not in the placebo group. However, the difference in ΔSD and ΔMAGE failed to reach statistical significance between two groups. No significant differences in the incidence of safety endpoints were observed between the two groups.Conclusion Dapagliflozin effectively decreased glucose levels, but not glucose variability, after 12 weeks of treatment in participants with type 2 diabetes mellitus receiving insulin treatment. The role of SGLT2 inhibitors in glycemic variability warrants further investigations.
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- Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis
- Complications
- Differences in Clinical Outcomes between Patients with and without Hypoglycemia during Hospitalization: A Retrospective Study Using Real-World Evidence
- Jeongmin Lee, Tong Min Kim, Hyunah Kim, Seung-Hwan Lee, Jae Hyoung Cho, Hyunyong Lee, Hyeon Woo Yim, Kun-Ho Yoon, Hun-Sung Kim
- Diabetes Metab J. 2020;44(4):555-565. Published online May 8, 2020
- DOI: https://doi.org/10.4093/dmj.2019.0064
- 6,504 View
- 101 Download
- 8 Web of Science
- 8 Crossref
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Abstract
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Background Some patients admitted to hospitals for glycemic control experience hypoglycemia despite regular meals and despite adhering to standard blood glucose control protocols. Different factors can have a negative impact on blood glucose control and prognosis after discharge. This study investigated risk factors for hypoglycemia and its effects on glycemic control during the hospitalization of patients in the general ward.
Methods This retrospective study included patients who were admitted between 2009 and 2018. Patients were provided regular meals at fixed times according to ideal body weights during hospitalization. We categorized the patients into two groups: those with and those without hypoglycemia during hospitalization.
Results Of the 3,031 patients, 379 experienced at least one episode of hypoglycemia during hospitalization (HYPO group). Hypoglycemia occurred more frequently particularly in cases of premixed insulin therapy. Compared with the control group, the HYPO group was older (61.0±16.8 years vs. 59.1±16.5 years,
P =0.035), with more females (60.4% vs. 49.6%,P <0.001), lower body mass index (BMI) (23.5±4.2 kg/m2 vs. 25.1±4.4 kg/m2,P <0.001), and higher prevalence of type 1 diabetes mellitus (6.1% vs. 2.6%,P <0.001), They had longer hospital stay (11.1±13.5 days vs. 7.6±4.6 days,P <0.001). After discharge the HYPO group had lower glycosylated hemoglobin reduction rate (−2.0%±0.2% vs. −2.5%±0.1%,P =0.003) and tended to have more frequent cases of cardiovascular disease.Conclusion Hypoglycemia occurred more frequently in older female patients with lower BMI and was associated with longer hospital stay and poorer glycemic control after discharge. Therefore, clinicians must carefully ensure that patients do not experience hypoglycemia during hospitalization.
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Citations
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Sung-Woo Kim
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Review
- Drug/Regimen
- Use of SGLT-2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Abdominal Obesity: An Asian Perspective and Expert Recommendations
- Wayne Huey-Herng Sheu, Siew Pheng Chan, Bien J. Matawaran, Chaicharn Deerochanawong, Ambrish Mithal, Juliana Chan, Ketut Suastika, Chin Meng Khoo, Huu Man Nguyen, Ji Linong, Andrea Luk, Kun-Ho Yoon
- Diabetes Metab J. 2020;44(1):11-32. Published online February 21, 2020
- DOI: https://doi.org/10.4093/dmj.2019.0208
- 8,767 View
- 199 Download
- 33 Web of Science
- 29 Crossref
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Abstract
PDFPubReader
The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.
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Original Articles
- Clinical Diabetes & Therapeutics
- Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study
- Hae Kyung Yang, Seung-Hwan Lee, Juyoung Shin, Yoon-Hee Choi, Yu-Bae Ahn, Byung-Wan Lee, Eun Jung Rhee, Kyung Wan Min, Kun-Ho Yoon
- Diabetes Metab J. 2019;43(3):287-301. Published online December 20, 2018
- DOI: https://doi.org/10.4093/dmj.2018.0054
- 5,876 View
- 104 Download
- 14 Web of Science
- 14 Crossref
-
Abstract
PDFSupplementary MaterialPubReader
Background We evaluated the efficacy and safety of acarbose add-on therapy in Korean patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled with metformin and sitagliptin.
Methods A total of 165 subjects were randomized to metformin and sitagliptin (Met+Sita,
n =65), metformin, sitagliptin, and acarbose (Met+Sita+Acarb,n =66) and sitagliptin and acarbose (Sita+Acarb, exploratory assessment,n =34) therapy in five institutions in Korea. After 16 weeks of acarbose add-on or metformin-switch therapy, a triple combination therapy was maintained from week 16 to 24.Results The add-on of acarbose (Met+Sita+Acarb group) demonstrated a 0.44%±0.08% (
P <0.001 vs. baseline) decrease in glycosylated hemoglobin (HbA1c) at week 16, while changes in HbA1c were insignificant in the Met+Sita group (−0.09%±0.10%,P =0.113). After 8 weeks of triple combination therapy, HbA1c levels were comparable between Met+Sita and Met+Sita+Acarb group (7.66%±0.13% vs. 7.47%±0.12%,P =0.321). Acarbose add-on therapy demonstrated suppressed glucagon secretion (area under the curve of glucagon, 4,726.17±415.80 ng·min/L vs. 3,314.38±191.63 ng·min/L,P =0.004) in the absence of excess insulin secretion during the meal tolerance tests at week 16 versus baseline. The incidence of adverse or serious adverse events was similar between two groups.Conclusion In conclusion, a 16-week acarbose add-on therapy to metformin and sitagliptin, effectively lowered HbA1c without significant adverse events. Acarbose might be a good choice as a third-line therapy in addition to metformin and sitagliptin in Korean subjects with T2DM who have predominant postprandial hyperglycemia and a high carbohydrate intake.
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Citations
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Ali Mohammadian, Sahand Tehrani Fateh, Mahlagha Nikbaf-Shandiz, Fatemeh Gholami, Niloufar Rasaei, Hossein Bahari, Samira Rastgoo, Reza Bagheri, Farideh Shiraseb, Omid Asbaghi
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Sameh S. Elhady, Noha M. Alshobaki, Mahmoud A. Elfaky, Abdulrahman E. Koshak, Majed Alharbi, Reda F. A. Abdelhameed, Khaled M. Darwish
Metabolites.2023; 13(8): 942. CrossRef - Change of metformin concentrations in the liver as a pharmacological target site of metformin after long-term combined treatment with ginseng berry extract
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- Complications
- Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus
- Yeoree Yang, Eun-Young Lee, Jae-Hyoung Cho, Yong-Moon Park, Seung-Hyun Ko, Kun-Ho Yoon, Moo-Il Kang, Bong-Yun Cha, Seung-Hwan Lee
- Diabetes Metab J. 2018;42(6):496-512. Published online September 28, 2018
- DOI: https://doi.org/10.4093/dmj.2018.0026
- 4,270 View
- 42 Download
- 10 Web of Science
- 9 Crossref
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Abstract
PDFSupplementary MaterialPubReader
Background This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus.
Methods In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements.
Results A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%).
Conclusion CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.
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Citations
Citations to this article as recorded by- Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions
Jingyang Chen, Dong Yin, Kefei Dou
Cardiovascular Diabetology.2023;[Epub] CrossRef - Long-Term Risk of Cardiovascular Disease Among Type 2 Diabetes Patients According to Average and Visit-to-Visit Variations of HbA1c Levels During the First 3 Years of Diabetes Diagnosis
Hyunah Kim, Da Young Jung, Seung-Hwan Lee, Jae-Hyoung Cho, Hyeon Woo Yim, Hun-Sung Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef - Factors Associated with Diabetic Complication Index among Type 2 Diabetes Patients: Focusing on Regular Outpatient Follow-up and HbA1c Variability
Haejung Lee, Gaeun Park, Ah Reum Khang
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Natsumi Matsuoka-Uchiyama, Haruhito A. Uchida, Shugo Okamoto, Yasuhiro Onishi, Katsuyoshi Katayama, Mariko Tsuchida-Nishiwaki, Hidemi Takeuchi, Rika Takemoto, Yoshiko Hada, Ryoko Umebayashi, Naoko Kurooka, Kenji Tsuji, Jun Eguchi, Hirofumi Nakajima, Kenic
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Xiaochun Zhang, Xue Yang, Bao Sun, Chunsheng Zhu
Communications Biology.2021;[Epub] CrossRef - Assessment of Functions of the Autonomic Nervous System in the Elderly with Different Comorbid Factors
Sushma S., Medha Y. Rao, Shaikh Mohammed Aslam
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Rosalia Dettori, Andrea Milzi, Kathrin Burgmaier, Mohammad Almalla, Martin Hellmich, Nikolaus Marx, Sebastian Reith, Mathias Burgmaier
Cardiovascular Diabetology.2020;[Epub] CrossRef - HbA1C Variability Is Strongly Associated With the Severity of Cardiovascular Autonomic Neuropathy in Patients With Type 2 Diabetes After Longer Diabetes Duration
Yun-Ru Lai, Chih-Cheng Huang, Wen-Chan Chiu, Rue-Tsuan Liu, Nai-Wen Tsai, Hung-Chen Wang, Wei-Che Lin, Ben-Chung Cheng, Yu-Jih Su, Chih-Min Su, Sheng-Yuan Hsiao, Pei-Wen Wang, Jung-Fu Chen, Cheng-Hsien Lu
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Alexander Steger, Alexander Müller, Petra Barthel, Michael Dommasch, Katharina Maria Huster, Katerina Hnatkova, Daniel Sinnecker, Alexander Hapfelmeier, Marek Malik, Georg Schmidt
Frontiers in Physiology.2019;[Epub] CrossRef
- Intensified glycemic control by HbA1c for patients with coronary heart disease and Type 2 diabetes: a review of findings and conclusions
- Epidemiology
- Serum Betatrophin Concentrations and the Risk of Incident Diabetes: A Nested Case-Control Study from Chungju Metabolic Disease Cohort
- Seung-Hwan Lee, Marie Rhee, Hyuk-Sang Kwon, Yong-Moon Park, Kun-Ho Yoon
- Diabetes Metab J. 2018;42(1):53-62. Published online November 3, 2017
- DOI: https://doi.org/10.4093/dmj.2018.42.1.53
- 3,603 View
- 52 Download
- 8 Web of Science
- 8 Crossref
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Abstract
PDFPubReader
Background Betatrophin is a newly identified hormone derived from the liver and adipose tissue, which has been suggested to regulate glucose and lipid metabolism. Circulating levels of betatrophin are altered in various metabolic diseases, although the results are inconsistent. We aimed to examine whether betatrophin is a useful biomarker in predicting the development of diabetes.
Methods A nested case-control study was performed using a prospective Chungju Metabolic disease Cohort Study. During a 4-year follow-up period, we analyzed 167 individuals who converted to diabetes and 167 non-converters, who were matched by age, sex, and body mass index. Serum betatrophin levels were measured by an ELISA (enzyme-linked immunosorbent assay).
Results Baseline serum betatrophin levels were significantly higher in the converter group compared to the non-converter group (1,315±598 pg/mL vs. 1,072±446 pg/mL,
P <0.001). After adjusting for age, sex, body mass index, fasting plasma glucose, systolic blood pressure, total cholesterol, and family history of diabetes, the risk of developing diabetes showed a stepwise increase across the betatrophin quartile groups. Subjects in the highest baseline quartile of betatrophin levels had more than a threefold higher risk of incident diabetes than the subjects in the lowest quartile (relative risk, 3.275; 95% confidence interval, 1.574 to 6.814;P =0.010). However, no significant relationships were observed between serum betatrophin levels and indices of insulin resistance or β-cell function.Conclusion Circulating levels of betatrophin could be a potential biomarker for predicting new-onset diabetes. Further studies are needed to understand the underlying mechanism of this association.
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Citations
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Faustino R. Pérez‐López, Junhua Yuan, Manuel Sánchez‐Prieto, María T. López‐Baena, Gonzalo R. Pérez‐Roncero, Seshadri Reddy Varikasuvu
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Hassan Tavassoli, Ali Heidarianpour
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Leonardo Catalano-Iniesta, Virginia Sánchez Robledo, María Carmen Iglesias-Osma, Amparo Galán Albiñana, Sixto Carrero, Enrique J. Blanco, Marta Carretero-Hernández, José Carretero, María José García-Barrado
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