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Review Article
Diabetes, obesity and metabolism
Contemporary Type 2 Diabetes Guidelines: Converging Evidence, Diverging Strategies, and the Position of the Korean Diabetes Association Framework
Suk Kyeong Kim, Dong-Lim Kim, Keeho Song, Shinae Kang, Byung-Wan Lee, Jong Han Choi
Endocrinol Metab. 2026;41(3):351-357.   Published online June 16, 2026
DOI: https://doi.org/10.3803/EnM.2026.3080
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AbstractAbstract PDFPubReader   ePub   
The pharmacological management of type 2 diabetes mellitus has changed markedly over the past decade, largely in response to evidence generated by cardiovascular and renal outcome trials. Although contemporary guidelines are informed by a broadly shared evidence base, they differ in how they organize treatment concepts and translate evidence into clinical algorithms. This review compares major diabetes guidelines from the American Diabetes Association (ADA), the National Institute for Health and Care Excellence (NICE), the Japan Diabetes Society (JDS), and the Korean Diabetes Association (KDA), with particular attention to pharmacological algorithms, comorbidity-driven treatment strategies, and the conceptual principles underlying each framework. The ADA guideline uses a person-centered, risk-based approach that prioritizes sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists for patients with cardiorenal disease. The NICE guideline applies a more structured strategy, recommending early dual or triple therapy within a cost-effectiveness framework. The JDS guideline emphasizes pathophysiology-based treatment selection tailored to East Asian populations. The KDA guideline retains a glycemia-centered treatment structure while incorporating comorbidity-based decision-making and allowing early, flexible combination therapy. Thus, despite substantial convergence in the evidence base, these guidelines differ in how cardiovascular risk, glycemic control, and pathophysiological heterogeneity are incorporated into treatment decisions. The KDA framework can be viewed as a pragmatic hybrid model that integrates these dimensions and is further extended by recent consensus efforts addressing disease severity and pathophysiology.
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Original Article
Diabetes, obesity and metabolism
Effectiveness and Safety of Oral Quadruple Combination Therapy in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis
Jaehyun Bae, Min Heui Yu, Minyoung Lee, Bong-Soo Cha, Byung-Wan Lee
Endocrinol Metab. 2025;40(2):258-267.   Published online January 13, 2025
DOI: https://doi.org/10.3803/EnM.2024.2120
  • 9,160 View
  • 249 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Achieving optimal glucose control is essential in the management of type 2 diabetes (T2D). This study aimed to evaluate the effectiveness and safety of oral quadruple combination therapy for the treatment of T2D.
Methods
This meta-analysis reviewed original research on oral quadruple combination therapy for T2D, including both experimental and observational studies with a minimum duration of 12 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to follow-up. The secondary endpoint was the incidence rate of adverse events. Two investigators independently extracted data and assessed the risk of bias. Outcomes were pooled as the standardized mean difference (using Hedge’s g) and the risk ratio for adverse events in random-effects meta-analyses.
Results
The meta-analysis included 17 studies. Oral quadruple combination therapy resulted in an additional mean reduction in HbA1c levels of 1.1% in patients who did not achieve glycemic control with oral triple combination therapy. Compared with switching to injectables, such as insulin or a glucagon-like peptide-1 receptor agonist–containing regimen, this therapy was non-inferior, even demonstrating a slightly superior glucose-lowering effect. Furthermore, it was determined to be safe, with an adverse event rate of 0.25, indicating no significant difference in safety compared with adding a placebo or switching to an injectable-containing regimen.
Conclusion
Oral quadruple combination therapy is a valid option for patients with T2D who are unable to achieve glycemic targets with oral triple combination therapy, offering both effective glycemic control and a favorable safety profile.

Citations

Citations to this article as recorded by  
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  • Contemporary Type 2 Diabetes Guidelines: Converging Evidence, Diverging Strategies, and the Position of the Korean Diabetes Association Framework
    Suk Kyeong Kim, Dong-Lim Kim, Keeho Song, Shinae Kang, Byung-Wan Lee, Jong Han Choi
    Endocrinology and Metabolism.2026; 41(3): 351.     CrossRef
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    Türkan Tüzün, Ayten Eraydın
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    Ancuța Dinu (Iacob), Luminita-Georgeta Confederat, Ionut Dragostin, Ionela Daniela Morariu, Dana Tutunaru, Oana-Maria Dragostin
    Current Issues in Molecular Biology.2025; 47(9): 709.     CrossRef
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    Jong Han Choi
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  • Bridging Evidence and Practice: A Consensus Statement from the Korean Diabetes Association on Diabetes Screening, Pharmacological Treatment and Severe Diabetes
    Jong Han Choi, Shinae Kang, Soo-Kyung Kim, Won Jun Kim, Ji Min Kim, Jaehyun Bae, Jae-Seung Yun, Eonju Jeon, Young-Eun Kim, Jae Hyun Bae, Hun Jee Choe, Young Min Cho, Seung-Hyun Ko, Sang Yong Kim, Hae Jin Kim, You-Cheol Hwang, Min Kyong Moon, Suk Chon, Seo
    Diabetes & Metabolism Journal.2025; 49(6): 1155.     CrossRef
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Review Article
Diabetes, obesity and metabolism
Initial Combination Therapy in Type 2 Diabetes
Ji Yoon Kim, Nam Hoon Kim
Endocrinol Metab. 2024;39(1):23-32.   Published online November 30, 2023
DOI: https://doi.org/10.3803/EnM.2023.1816
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  • 1,372 Download
  • 20 Web of Science
  • 26 Crossref
AbstractAbstract PDFPubReader   ePub   
Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved β-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Citations

Citations to this article as recorded by  
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    Hariballav Mahapatra, Piyush Kumar Gupta, Ajo Paul, Amit Nampalliwar, Manju Bansal, Baijnath Das, K. Parameswaran Namboothiri
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  • Clinical Experience and Outcomes with Triple-drug Fixed-dose Combination Therapy (Sitagliptin + Dapagliflozin + Metformin Sustained-Release Tablets) in Type 2 Diabetes Mellitus Management: A Real-world Observational Survey of Clinician Perspectives
    Manoj Arajanbhai Suva
    Archives of Medicine and Health Sciences.2026; 14(1): 61.     CrossRef
  • Circulating GDF15 levels reflect metabolic and inflammatory burden in early dysglycemia: findings from the ADIOS cohort
    Ji Yoon Kim, Ah Hyeon Lee, Jiyoon Lee, Hye-Min Jang, Sin Gon Kim, Dong-Hoon Kim, Nam Hoon Kim
    Diabetes Research and Clinical Practice.2026; 239: 113461.     CrossRef
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Original Article
Clinical Study
Big Data Articles (National Health Insurance Service Database)
Effect of Teneligliptin versus Sulfonylurea on Major Adverse Cardiovascular Outcomes in People with Type 2 Diabetes Mellitus: A Real-World Study in Korea
Da Hea Seo, Kyoung Hwa Ha, So Hun Kim, Dae Jung Kim
Endocrinol Metab. 2021;36(1):70-80.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.777
  • 11,762 View
  • 245 Download
  • 7 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Results regarding the cardiovascular (CV) effects of dipeptidyl peptidase-4 (DPP-4) inhibitors are inconsistent. This study aimed to assess the effects of teneligliptin, a DPP-4 inhibitor, on the risk of major CV outcomes in type 2 diabetes mellitus (T2DM) patients compared to sulfonylurea.
Methods
From January 1, 2015 to December 31, 2017, we conducted a retrospective cohort study using the Korean National Health Insurance Service database. A total of 6,682 T2DM patients who were newly prescribed DPP-4 inhibitors or sulfonylurea were selected and matched in a 1:1 ratio by propensity score. The hazard ratios (HRs) for all-cause mortality, hospitalization for heart failure (HHF), all-cause mortality or HHF, myocardial infarction (MI), stroke, and hypoglycemia were assessed.
Results
During 641 days of follow-up, the use of teneligliptin was not associated with an increased risk of all-cause mortality (HR, 1.00; 95% confidence interval [CI], 0.85 to 1.19), HHF (HR, 0.99; 95% CI, 0.86 to 1.14), all-cause mortality or HHF (HR, 1.02; 95% CI, 0.90 to 1.14), MI (HR, 0.90; 95% CI, 0.68 to 1.20), and stroke (HR, 1.00; 95% CI, 0.86 to 1.17) compared to the use of sulfonylurea. However, it was associated with a significantly lower risk of hypoglycemia (HR, 0.68; 95% CI, 0.49 to 0.94) compared to sulfonylurea therapy.
Conclusion
Among T2DM patients, teneligliptin therapy was not associated with an increased risk of CV events including HHF, but was associated with a lower risk of hypoglycemia compared to sulfonylurea therapy.

Citations

Citations to this article as recorded by  
  • Association between age at diagnosis of type 2 diabetes and cardiovascular morbidity and mortality risks: A nationwide population-based study
    Da Hea Seo, Mina Kim, Young Ju Suh, Yongin Cho, Seong Hee Ahn, Seongbin Hong, So Hun Kim
    Diabetes Research and Clinical Practice.2024; 208: 111098.     CrossRef
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    Da Hea Seo, Mina Kim, Yongin Cho, Seong Hee Ahn, Seongbin Hong, So Hun Kim
    Journal of Clinical Medicine.2024; 13(15): 4386.     CrossRef
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    Jari Delbaere, Ewoud Deboever, Bert Vaes, Frank Nobels, Pavlos Mamouris, Geert Goderis
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    R. Pelluri, S. Kongara, V. R. Nagasubramanian, S. Mahadevan, J. Chimakurthy
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    Harmanjit Singh, Ekta Arora, Seerat Narula, Mandeep Singla, Armaan Otaal, Jatin Sharma
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    Yewon Na, Soo Wan Kim, Ie Byung Park, Soo Jung Choi, Seungyoon Nam, Jaehun Jung, Dae Ho Lee
    The Journal of Clinical Endocrinology & Metabolism.2022; 107(11): 3022.     CrossRef
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Review Articles
Diabetes, Obesity and Metabolism
The Role of Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Reducing Cardiovascular Events in Patients with Type 2 Diabetes
Gwang Sil Kim, Joong Hyun Park, Jong Chul Won
Endocrinol Metab. 2019;34(2):106-116.   Published online May 9, 2019
DOI: https://doi.org/10.3803/EnM.2019.34.2.106
  • 10,603 View
  • 126 Download
  • 18 Web of Science
  • 18 Crossref
AbstractAbstract PDFPubReader   ePub   

The prevalence of type 2 diabetes mellitus (T2DM), which is associated with cardiovascular morbidity and mortality, is increasing worldwide. Although there have been advances in diabetes treatments that reduce microvascular complications (nephropathy, neuropathy, retinopathy), many clinical studies have found that conventional oral hypoglycemic agents and glucose control alone failed to reduce cardiovascular disease. Thus, incretin-based therapies including glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) represent a new area of research, and may serve as novel therapeutics for treating hyperglycemia and modifying other cardiovascular risk factors. Recently, it has been confirmed that several drugs in these classes, including canagliflozin, empagliflozin, semaglutide, and liraglutide, are safe and possess cardioprotective effects. We review the most recent cardiovascular outcome trials on GLP-1RAs and SGLT-2Is, and discuss their implications for treating patients with T2DM in terms of protective effects against cardiovascular disease.

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Diabetes, Obesity and Metabolism
Diabetes Drugs and Cardiovascular Safety
Ji Cheol Bae
Endocrinol Metab. 2016;31(2):239-244.   Published online June 10, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.239
  • 10,507 View
  • 56 Download
  • 15 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   

Diabetes is a well-known risk factor of cardiovascular morbidity and mortality, and the beneficial effect of improved glycemic control on cardiovascular complications has been well established. However, the rosiglitazone experience aroused awareness of potential cardiovascular risk associated with diabetes drugs and prompted the U.S. Food and Drug Administration to issue new guidelines about cardiovascular risk. Through postmarketing cardiovascular safety trials, some drugs demonstrated cardiovascular benefits, while some antidiabetic drugs raised concern about a possible increased cardiovascular risk associated with drug use. With the development of new classes of drugs, treatment options became wider and the complexity of glycemic management in type 2 diabetes has increased. When choosing the appropriate treatment strategy for patients with type 2 diabetes at high cardiovascular risk, not only the glucose-lowering effects, but also overall benefits and risks for cardiovascular disease should be taken into consideration.

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Original Article
Diabetes, Obesity and Metabolism
Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors
Soyeon Yoo, Sang-Ouk Chin, Sang-Ah Lee, Gwanpyo Koh
Endocrinol Metab. 2015;30(3):352-360.   Published online August 4, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.3.352
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AbstractAbstract PDFSupplementary MaterialPubReader   
Background

The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).

Methods

We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations.

Results

GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (β=0.209, P=0.009) and MAG (β=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk.

Conclusion

GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

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