Diabetes & Metabolism Journal

Review

Complications
Clinical Phenotypes of Diabetic Peripheral Neuropathy: Implications for Phenotypic-Based Therapeutics Strategies: Jie-Eun Lee, Jong Chul Won; Diabetes Metab J. 2025;49(4):542-564. Published online July 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0299

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Abstract PDF: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus that encompasses a heterogeneous group of conditions with diverse clinical manifestations. Despite its prevalence, no universally established classification or treatment approach is currently available. Recent findings have underscored the role of systemic inflammation, oxidative stress, and neurochemical imbalances in shaping DPN phenotypes, emphasizing the need for phenotype-specific diagnostic and therapeutic approaches. Advanced diagnostic techniques, including magnetic resonance imaging-based neuroimaging and quantitative sensory testing, are emerging as tools for phenotypic characterization. Therapeutic interventions are moving toward precision medicine, with targeted pharmacological and non-pharmacological strategies tailored to specific clinical presentations. Innovations such as digital health platforms, regenerative therapies, and combinatorial pharmacotherapy are promising for addressing primary neuropathic pain and its associated complications. This review synthesizes the current evidence on DPN phenotypes (painful, painless, and mixed forms), their underlying pathophysiological mechanisms, and the efficacy of treatment approaches. A framework for optimizing management strategies is also proposed. By leveraging novel insights into sensory phenotypes and treatment responsiveness, clinicians can adopt DPN phenotype-based treatment models to optimize patient care, improve treatment outcomes, reduce the substantial disease burden, and enhance patient quality of life.

Original Article

Drug/Regimen
Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial: Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee; Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Citations

Citations to this article as recorded by

Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
Expert Opinion on Drug Safety.2025; 24(3): 305. CrossRef
Exploration of metformin-based drug combination for mitigating diabetes-associated atherosclerotic diseases
Biao Qu, Zheng Li, Wei Hu
World Journal of Diabetes.2025;[Epub] CrossRef

Editorial

Obesity and Metabolic Syndrome
Simply the Best: Anthropometric Indices for Predicting Cardiovascular Disease: Jie-Eun Lee; Diabetes Metab J. 2019;43(2):156-157. Published online April 15, 2019; DOI: https://doi.org/10.4093/dmj.2019.0057

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Citations

Citations to this article as recorded by

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BMC Gastroenterology.2025;[Epub] CrossRef
Body roundness index and the risk of hypertension: a prospective cohort study in Southwest China
Qingqing Zhan, Qinyu An, Fuyan Zhang, Tianlin Zhang, Tao Liu, Yiying Wang
BMC Public Health.2024;[Epub] CrossRef
Physical performance and glycemic control under SGLT-2-inhibitors in patients with type 2 diabetes and established atherosclerotic cardiovascular diseases or high cardiovascular risk (PUSH): Design of a 4-week prospective observational study
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Frontiers in Cardiovascular Medicine.2022;[Epub] CrossRef

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