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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 Metab J. 2024;48(2):312-320.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2022.0421
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  • 1 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
There is still a lack of research on which diabetic drugs are more effective in preventing stroke. Our network metaanalysis aimed to compare cerebrovascular benefits among glucose-lowering treatments.
Methods
We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the ClinicalTrials.gov registry for clinical trials from inception through May 25, 2021. We included both prespecified cerebrovascular outcomes and cerebrovascular events reported as severe adverse events. Subgroup analyses were conducted by stroke subtype, publication type, age of patients, baseline glycosylated hemoglobin (HbA1c), duration of type 2 diabetes mellitus, and cardiovascular risks.
Results
Of 2,861 reports and 1,779 trials screened, 79 randomized controlled trials comprising 206,387 patients fulfilled the inclusion criteria. In the pairwise meta-analysis, the use of glucagon-like peptide-1 (GLP-1) agonist was associated with a lower risk of total stroke compared with placebo (relative risk [RR], –0.17; 95% confidence interval [CI], –0.27 to –0.07). In the network meta- analysis, only the use of sodium-glucose cotransporter-2 (SGLT-2) inhibitor was associated with a reduction of total stroke, compared with placebo (RR, 0.81; 95% CI, 0.67 to 0.98). In the subgroup analyses, the use of SGLT-2 inhibitor and GLP-1 agonist was associated with a lower risk of stroke in those with high HbA1c (≥8.0) and low-risk of cardiovascular disease, respectively.
Conclusion
SGLT-2 inhibitors and GLP-1 agonists were shown to be beneficial for stroke prevention in patients with type 2 diabetes mellitus.

Citations

Citations to this article as recorded by  
  • SGLT2 Inhibitors and GLP-1 Agonists: A Beacon of Hope for Stroke Prevention in Diabetes
    Jae-Han Jeon
    Diabetes & Metabolism Journal.2024; 48(2): 213.     CrossRef
  • Reply to comment on: Association of glucose-lowering drugs with incident stroke and transient ischaemic attacks in primary care patients with type 2 diabetes: disease analyser database
    Wolfgang Rathmann, Karel Kostev
    Acta Diabetologica.2024;[Epub]     CrossRef
Cardiovascular Risk/Epidemiology
Psychotic Disorders and the Risk of Type 2 Diabetes Mellitus, Atherosclerotic Cardiovascular Diseases, and All-Cause Mortality: A Population-Based Matched Cohort Study
You-Bin Lee, Hyewon Kim, Jungkuk Lee, Dongwoo Kang, Gyuri Kim, Sang-Man Jin, Jae Hyeon Kim, Hong Jin Jeon, Kyu Yeon Hur
Diabetes Metab J. 2024;48(1):122-133.   Published online January 3, 2024
DOI: https://doi.org/10.4093/dmj.2022.0431
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The effects of psychotic disorders on cardiometabolic diseases and premature death need to be determined in Asian populations.
Methods
In this population-based matched cohort study, the Korean National Health Insurance Service database (2002 to 2018) was used. The risk of type 2 diabetes mellitus (T2DM), acute myocardial infarction (AMI), ischemic stroke, composite of all cardiometabolic diseases, and all-cause death during follow-up was compared between individuals with psychotic disorders treated with antipsychotics (n=48,162) and 1:1 matched controls without psychiatric disorders among adults without cardiometabolic diseases before or within 3 months after baseline.
Results
In this cohort, 53,683 composite cases of all cardiometabolic diseases (during median 7.38 years), 899 AMI, and 1,216 ischemic stroke cases (during median 14.14 years), 7,686 T2DM cases (during median 13.26 years), and 7,092 deaths (during median 14.23 years) occurred. The risk of all outcomes was higher in subjects with psychotic disorders than matched controls (adjusted hazard ratios [95% confidence intervals]: 1.522 [1.446 to 1.602] for T2DM; 1.455 [1.251 to 1.693] for AMI; 1.568 [1.373 to 1.790] for ischemic stroke; 1.595 [1.565 to 1.626] for composite of all cardiometabolic diseases; and 2.747 [2.599 to 2.904] for all-cause mortality) during follow-up. Similar patterns of associations were maintained in subgroup analyses but more prominent in younger individuals (P for interaction <0.0001) when categorized as those aged 18–39, 40–64, or ≥65 years.
Conclusion
Patients with psychotic disorders treated with antipsychotics were associated with increased risk of premature allcause mortality and cardiometabolic outcomes in an Asian population. This relationship was more pronounced in younger individuals, especially aged 18 to 39 years.
Cardiovascular Risk/Epidemiology
Comparative Effects of Sodium-Glucose Cotransporter 2 Inhibitor and Thiazolidinedione Treatment on Risk of Stroke among Patients with Type 2 Diabetes Mellitus
Seung Eun Lee, Hyewon Nam, Han Seok Choi, Hoseob Kim, Dae-Sung Kyoung, Kyoung-Ah Kim
Diabetes Metab J. 2022;46(4):567-577.   Published online February 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0160
  • 5,356 View
  • 357 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.
Methods
Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).
Results
After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.
Conclusion
In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

Citations

Citations to this article as recorded by  
  • Similar incidence of stroke with SGLT2 inhibitors and GLP-1 receptor agonists in real-world cohort studies among patients with type 2 diabetes
    André J. Scheen
    Diabetes Epidemiology and Management.2024; 13: 100179.     CrossRef
  • Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
    Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
  • Do SGLT2 inhibitors and GLP-1 receptor agonists modulate differently the risk of stroke ? Discordance between randomised controlled trials and observational studies
    André J. Scheen
    Diabetes & Metabolism.2023; 49(5): 101474.     CrossRef
Cardiovascular Risk/Epidemiology
Metabolic Syndrome Severity Score for Predicting Cardiovascular Events: A Nationwide Population-Based Study from Korea
Yo Nam Jang, Jun Hyeok Lee, Jin Sil Moon, Dae Ryong Kang, Seong Yong Park, Jerim Cho, Jang-Young Kim, Ji Hye Huh
Diabetes Metab J. 2021;45(4):569-577.   Published online January 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0103
  • 6,446 View
  • 223 Download
  • 13 Web of Science
  • 14 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population.
Methods
From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve.
Results
Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III.
Conclusion
The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.

Citations

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  • Metabolic syndrome awareness in the general Korean population: results from a nationwide survey
    Hyun-Jin Kim, Mi-Seung Shin, Kyung-Hee Kim, Mi-Hyang Jung, Dong-Hyuk Cho, Ju-Hee Lee, Kwang Kon Koh
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    Sofia Makishi Schlenker, Sofia Inez Munhoz, André Rochinski Busanello, Matheus Guedes Sanches, Barbara Stadler Kahlow, Renato Nisihara, Thelma Larocca Skare
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    Ji Hye Huh, Kyong Joo Lee, Yun Kyung Cho, Shinje Moon, Yoon Jung Kim, Eun Roh, Kyung-do Han, Dong Hee Koh, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
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    V. V. Sverchkov, E. V. Bykov
    Journal Biomed.2023; 19(2): 61.     CrossRef
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    Ji Yoon Kim, Kyoung Jin Kim, Kyeong Jin Kim, Jimi Choi, Jinhee Seo, Jung-Been Lee, Jae Hyun Bae, Nam Hoon Kim, Hee Young Kim, Soo-Kyung Lee, Sin Gon Kim
    Journal of Medical Internet Research.2023; 25: e45975.     CrossRef
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    Mohammadjavad Honarvar, Ladan Mehran, Safdar Masoumi, Sadaf Agahi, Shayesteh Khalili, Fereidoun Azizi, Atieh Amouzegar
    Scientific Reports.2023;[Epub]     CrossRef
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    Ji Hye Huh, Sang Wook Park, Tae-Hwa Go, Dae Ryong Kang, Sang-Hak Lee, Jang-Young Kim
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
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Drug/Regimen
Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus
Ja Young Jeon, Kyoung Hwa Ha, Dae Jung Kim
Diabetes Metab J. 2021;45(4):505-514.   Published online October 30, 2020
DOI: https://doi.org/10.4093/dmj.2020.0057
  • 7,833 View
  • 341 Download
  • 10 Web of Science
  • 11 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.
Methods
This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs).
Results
After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.
Conclusion
SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.

Citations

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Review
Obesity and Metabolic Syndrome
Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases
Eugene Han, Yong-ho Lee
Diabetes Metab J. 2017;41(6):430-437.   Published online November 17, 2017
DOI: https://doi.org/10.4093/dmj.2017.41.6.430
  • 4,882 View
  • 86 Download
  • 50 Web of Science
  • 54 Crossref
AbstractAbstract PDFPubReader   

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.

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Original Article
Higher Glycated Hemoglobin Level Is Associated with Increased Risk for Ischemic Stroke in Non-Diabetic Korean Male Adults
Hyung Geun Oh, Eun-Jung Rhee, Tae-Woong Kim, Kyung Bok Lee, Jeong-Ho Park, Kwang-Ik Yang, Dushin Jeong, Hyung-Kook Park
Diabetes Metab J. 2011;35(5):551-557.   Published online October 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.5.551
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AbstractAbstract PDFPubReader   
Background

The role of glycated hemoglobin (HbA1c) in the prediction of ischemic stroke in non-diabetic subjects is not clear. We performed a study to analyze the role of HbA1c in the risk prediction of ischemic stroke in non-diabetic Korean males adult.

Methods

A total of 307 non-diabetic male patients with ischemic stroke were enrolled, and 253 age-matched control subjects without a history of diabetes, hypertension, or cardiovascular disease were selected from a Health Check-up database. Anthropometric measurement data, fasting glucose level, lipid profile, and HbA1c level were available for all subjects. Associations of the variables and the presence or absence of ischemic stroke were analyzed.

Results

The ischemic stroke patient group had significantly higher HbA1c levels (5.8±0.5% vs. 5.5±0.5%, P<0.01) and mean systolic and diastolic blood pressure compared with the control group. Among the variables, smoking, low high density lipoprotein cholesterol, systolic blood pressure, and HbA1c were the significant determinants for ischemic stroke. The highest quartile of HbA1c showed a 9.6-fold increased odds ratio for ischemic stroke compared with the lowest quartile of HbA1c (odds ratio, 9.596; 95% confidence interval, 3.859 to 23.863, P<0.01). The proportion of ischemic stroke patients showed a significant trend for increment as the deciles of HbA1c increased (P for trend <0.01).

Conclusion

Higher HbA1c indicated a significantly increased risk for ischemic stroke after adjusting for other confounding variables in non-diabetic Korean adult males. HbA1c might have significance in predicting the risk for ischemic stroke even in the non-diabetic range.

Citations

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Diabetes Metab J : Diabetes & Metabolism Journal