Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study

Chan, Cheng-Wei; Yu, Chu-Leng; Lin, Ji-Ping; Hsieh, Yu‐Cheng; Lin, Chun‐Pin; Hung, Chi‐Ren; Li, Cheng-Hung; Liao, Ying‐Chieh; Lo, Chung Ping; Huang, Jin‐Long; Lin, Ching‐Heng; Wu, Tsu‐Juey

doi:10.1186/s12933-018-0663-6

Cited by 44 publications

(31 citation statements)

References 51 publications

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“…Also, they report an elevated risk for add‐on sulfonylureas compared with add‐on thiazolidinediones (specifically pioglitazone). Similar findings have been found from data from other healthcare systems, such as the Taiwan National Health Insurance Database , the Swedish National Diabetes Registry and the Korean National Health Insurance Database .…”

Section: Discussionsupporting

confidence: 87%

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

2018

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Aim To examine the risks of all‐cause mortality and cardiovascular events associated with adding vs switching to second‐line therapies in a comparative safety study of people with Type 2 diabetes mellitus. Methods We conducted a retrospective cohort study using an as‐treated analysis of people served by the Veterans Health Administration who were on metformin and subsequently augmented this treatment or switched to other oral glucose‐lowering treatments between 1998 and 2012. This study included 145 250 people with long follow‐up. Confounding was addressed through several strategies, involving weighted propensity score models with rich confounder adjustment and strict inclusion criteria, coupled with an incident‐user design. Results Second‐line use of sulfonylureas was related to higher mortality (hazard ratio 1.39, 95% CI 1.14, 1.70) and cardiovascular risks (hazard ratio 1.19, 95% CI 1.09, 1.30) compared with thiazolidinedione therapy. Differential hazards were associated with discontinuing or not discontinuing metformin; switching to sulfonylurea therapy was associated with a higher risk of all‐cause mortality and cardiovascular events compared with all other therapies. Furthermore, add‐on sulfonylurea therapy was associated with an elevated risk for both outcomes when compared with thiazolidinedione add‐on therapy. Conclusions The results of the present study may inform decisions on whether to augment or discontinue metformin; when considering the long‐term risks, switching to a sulfonylurea appears unfavourable compared with other therapies. Instead, adding a thiazolidinedione to existing metformin therapy appears to be superior to adding or switching to a sulfonylurea.

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Section: Discussionsupporting

confidence: 87%

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

2018

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“…Twenty years ago, experimental evidence showed that lowering blood glucose reduced the risk of microvascular complications among patients with type 2 diabetes [33,60,61]. Several studies have subsequently indicated that metformin decreased mortality and adverse cardiovascular events [62][63][64][65][66]. A large nationwide study revealed that patients treated with metformin had significantly lower all-cause mortality than those treated with sulfonylureas (including glimepiride, glyburide, glipizide, and tolbutamide) [54].…”

Section: Discussionmentioning

confidence: 99%

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

Han

Xie

Liu

et al. 2019

Cardiovasc Diabetol

250

150

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Background Metformin is the most widely prescribed drug to lower glucose and has a definitive effect on the cardiovascular system. The goal of this systematic review and meta-analysis is to assess the effects of metformin on mortality and cardiac function among patients with coronary artery disease (CAD). Methods Relevant studies reported before October 2018 was retrieved from databases including PubMed, EMBASE, Cochrane Library and Web of Science. Hazard ratio (HR) was calculated to evaluate the all-cause mortality, cardiovascular mortality and incidence of cardiovascular events (CV events), to figure out the level of left ventricular ejection fraction (LVEF), creatine kinase MB (CK-MB), type B natriuretic peptide (BNP) and to compare the average level of low density lipoprotein (LDL). Results In this meta-analysis were included 40 studies comprising 1,066,408 patients. The cardiovascular mortality, all-cause mortality and incidence of CV events were lowered to adjusted HR (aHR) = 0.81, aHR = 0.67 and aHR = 0. 83 respectively after the patients with CAD were given metformin. Subgroup analysis showed that metformin reduced all-cause mortality in myocardial infarction (MI) (aHR = 0.79) and heart failure (HF) patients (aHR = 0.84), the incidence of CV events in HF (aHR = 0.83) and type II diabetes mellitus (T2DM) patients (aHR = 0.83), but had no significant effect on MI (aHR = 0.87) and non-T2DM patients (aHR = 0.92). Metformin is superior to sulphonylurea (aHR = 0.81) in effects on lowering the incidence of CV events and in effects on patients who don’t use medication. The CK-MB level in the metformin group was lower than that in the control group standard mean difference (SMD) = − 0.11). There was no significant evidence that metformin altered LVEF (MD = 2.91), BNP (MD = − 0.02) and LDL (MD = − 0.08). Conclusion Metformin reduces cardiovascular mortality, all-cause mortality and CV events in CAD patients. For MI patients and CAD patients without T2DM, metformin has no significant effect of reducing the incidence of CV events. Metformin has a better effect of reducing the incidence of CV events than sulfonylureas.

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“…In Asian T2DM patients without prior cardiovascular diseases, the real-world data also showed controversial protective effects of pioglitazone. Chan et al [32] demonstrated that pioglitazone added to metformin, compared to sulfonylurea plus metformin, may have fewer major cardiovascular events in T2DM patients. But another real-world study did not show the protective effects of pioglitazone on IS prevention [33].…”

Section: Discussionmentioning

confidence: 99%

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

Liu

Lee

Lin

et al. 2020

Cardiovasc Diabetol

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Background and aim: Peroxisome proliferator-activated receptor-γ (PPAR-γ) modulating treatment may have cardiovascular benefits in type 2 diabetes mellitus (T2DM) patients after ischemic stroke (IS). However, whether there are additional benefits from intensive PPAR-γ modulating treatments in Asian patients with T2DM and hypertension (HTN) after IS remains unknown.Methods: Between 2001 and 2013, patients admitted due to IS were identified from the National Health Insurance Research Database of Taiwan. Patients with T2DM and HTN using angiotensin receptor blockers were further included. Eligible patients were divided into two groups: (1) pioglitazone and (2) non-pioglitazone oral anti-diabetic agent groups. Propensity score matching (1:2) was used to balance the distribution of baseline characteristics, stroke severity and medications. The primary outcome was recurrent IS. Subgroup analysis for recurrent IS in pioglitazone and/or telmisartan users, the trend of IS risks across different PPAR-γ intensity treatments, and dose-dependent outcomes across different pioglitazone possession ratios were further studied. Statistical significance was set at p < 0.05 and p < 0.1 for clinical outcomes and interaction of subgroup analyses, respectively.Results: There were 3190 and 32,645 patients in the pioglitazone and non-pioglitazone groups. Patients of the pioglitazone group had a lower risk of recurrent IS (subdistribution hazard ratio, 0.91; 95% confidence interval 0.84-0.99). Pioglitazone was also associated with reduced recurrent IS in patients who also used telmisartan (p for interaction = 0.071). A graded correlation was found a borderline significant trend between the intensity of PPAR-γ therapy and following IS (p = 0.076). The dose-dependent outcome also showed that a borderline significant trend that higher pioglitazone possession ratio was associated with a lower risk of recurrent IS (p = 0.068). Conclusions:The current study suggests that the use of pioglitazone in type 2 diabetic and hypertensive IS patients is associated with fewer recurrent IS events in an Asian population. Concurrent telmisartan use or a higher pioglitazone possession ratio may have a trend of increased pleiotropic effects, which could possibly be related to higher PPAR-γ effects. Future studies are warranted to confirm or refute the clinical effects and the possible mechanism of more intensive PPAR-γ-modulating treatments. © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study

Cited by 44 publications

References 51 publications

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

Long‐term comparative safety analysis of the risks associated with adding or switching to a sulfonylurea as second‐line Type 2 diabetes mellitus treatment in a US veteran population

Effect of metformin on all-cause and cardiovascular mortality in patients with coronary artery diseases: a systematic review and an updated meta-analysis

Pioglitazone and PPAR-γ modulating treatment in hypertensive and type 2 diabetic patients after ischemic stroke: a national cohort study

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