Diabetes & Metabolism Journal

Reviews

Pharmacotherapy
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Diabetic Kidney Disease: Evolving Evidence and Clinical Application: Jae Hyun Bae; Diabetes Metab J. 2025;49(3):386-402. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0220

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Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and significantly increases cardiovascular risk and mortality. Despite conventional therapies, including renin-angiotensin-aldosterone system inhibitors, substantial residual risk remains. The emergence of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has reshaped DKD management. Beyond glycemic control, these agents provide distinct and complementary cardiorenal benefits through mechanisms such as hemodynamic modulation, anti-inflammatory effects, and metabolic adaptations. Landmark trials, including CREDENCE, DAPA-CKD, EMPA-KIDNEY, and FLOW, have demonstrated their efficacy in preserving kidney function and reducing adverse outcomes. SGLT2 inhibitors appear more effective in mitigating glomerular hyperfiltration and lowering heart failure risk, whereas GLP-1 receptor agonists are particularly beneficial in reducing albuminuria and atherosclerotic cardiovascular events. Although indirect comparisons suggest that SGLT2 inhibitors may offer greater protection against kidney function decline, direct head-to-head trials are lacking. Combination therapy holds promise, however further studies are needed to define optimal treatment strategies. This review synthesizes current evidence, evaluates comparative effectiveness, and outlines future directions in DKD management, emphasizing precision medicine approaches to enhance clinical outcomes. The integration of these therapies represents a paradigm shift in diabetes care, expanding treatment options for people with diabetes mellitus at risk of kidney failure.

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Special Issue “Molecular Therapeutics for Diabetes and Related Complications”
Kota V. Ramana
International Journal of Molecular Sciences.2025; 26(12): 5585. CrossRef

Basic and Translational Research
Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies: Joon Seok Park, Kyu Sik Kim, Hyung Jin Choi; Diabetes Metab J. 2025;49(3):333-347. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0106

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Abstract PDF PubReader ePub: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate satiation and satiety. This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)—a key GLP-1RA target—mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

Original Article

Pharmacotherapy
Use of Glucagon-Like Peptide-1 Receptor Agonists Does Not Increase the Risk of Cancer in Patients with Type 2 Diabetes Mellitus: Mijin Kim, Seung Chan Kim, Jinmi Kim, Bo Hyun Kim; Diabetes Metab J. 2025;49(1):49-59. Published online October 24, 2024; DOI: https://doi.org/10.4093/dmj.2024.0105

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Abstract PDF Supplementary Material PubReader ePub

Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes mellitus (T2DM) given their extra-pancreatic effects. However, there are concerns about carcinogenesis in the pancreas and thyroid gland. We aimed to evaluate the site-specific incidence of cancer in patients with T2DM-treated GLP-1 RAs using a nationwide cohort.
Methods
This study included data obtained from the Korean National Health Insurance Service (between 2004 and 2021). The primary outcome was newly diagnosed cancer, and the median follow-up duration for all participants was 8 years.
Results
After propensity score matching, 7,827 participants were analyzed; 2,609 individuals each were included in the GLP-1 RA, diabetes mellitus (DM) control, and non-DM control groups. The incidence rate ratio (IRR) of subsequent cancer in patients with T2DM was 1.73, which was higher than that of individuals without DM, and it increased in both men and women. Analysis of patients with T2DM showed no increased cancer risk associated with the use of GLP-1 RA, and similar results were observed in both men and women. The IRRs of pancreatic cancer (0.74), thyroid cancer (1.32), and medullary thyroid cancer (0.34) did not significantly increase in the GLP-1 RA group compared with those in the DM control group.
Conclusion
There was a 73% higher risk of cancer in patients with T2DM compared with the general population. However, among patients with T2DM, there was no association between the use of GLP-1 RAs and new-onset cancers, including pancreatic and medullary thyroid cancers.

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GLP‐1 receptor agonists and the risk for cancer: A meta‐analysis of randomized controlled trials
Giovanni Antonio Silverii, Christian Marinelli, Costanza Bettarini, Gloria Giovanna Del Vescovo, Matteo Monami, Edoardo Mannucci
Diabetes, Obesity and Metabolism.2025;[Epub] CrossRef

Review

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea: Seungjoon Oh, Suk Chon, Kyu Jeong Ahn, In-Kyung Jeong, Byung-Joon Kim, Jun Goo Kang; Diabetes Metab J. 2015;39(3):177-187. Published online June 15, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.177

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Abstract PDF PubReader

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce glycosylated hemoglobin (HbA1c, 0.5% to 1.0%), and are associated with moderate weight loss and a relatively low risk of hypoglycemia. There are differences between Asian and non-Asian populations. We reviewed available data on GLP-1RAs, focusing on Korean patients, to better understand their risk/benefit profile and help inform local clinical practice. Control of postprandial hyperglycemia is important in Asians in whom the prevalence of post-challenge hyperglycemia is higher (vs. non-Asians). The weight lowering effects of GLP-1RAs are becoming more salient as the prevalence of overweight and obesity among Korean patients increases. The higher rate of gastrointestinal adverse events amongst Asian patients in clinical trials may be caused by higher drug exposure due to the lower body mass index of the participants (vs. non-Asian studies). Data on the durability of weight loss, clinically important health outcomes, safety and optimal dosing in Korean patients are lacking. Use of GLP-1RAs is appropriate in several patient groups, including patients whose HbA1c is uncontrolled, especially if this is due to postprandial glucose excursions and patients who are overweight or obese due to dietary problems (e.g., appetite control). The potential for gastrointestinal adverse events should be explained to patients at treatment initiation to facilitate the promotion of better compliance.

Citations

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Safety and Effectiveness of Dulaglutide in the Treatment of Type 2 Diabetes Mellitus: A Korean Real-World Post-Marketing Study
Jeonghee Han, Woo Je Lee, Kyu Yeon Hur, Jae Hyoung Cho, Byung Wan Lee, Cheol-Young Park
Diabetes & Metabolism Journal.2024; 48(3): 418. CrossRef
Tolerability and Effectiveness of Switching to Dulaglutide in Patients With Type 2 Diabetes Inadequately Controlled With Insulin Therapy
Youngsook Kim, Ji Hye Huh, Minyoung Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
Frontiers in Endocrinology.2022;[Epub] CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef

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