Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors

Wu, Mei‐Zhen; Chandramouli, Chanchal; Wong, Pak-Kin; Chan, Yap-Hang; Li, Hang-Long; Yu, Si-Yeung; Tse, Yee‐Kit; Ren, Q W; Yu, Shuk-Yin; Tse, Hung‐Fat; Lam, Carolyn S.P.; Yiu, Kai‐Hang

doi:10.1016/j.diabet.2022.101367

Cited by 22 publications

(21 citation statements)

References 41 publications

(42 reference statements)

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“…I have read with great interest the results of the large, observational study conducted by Ng et al (1), who demonstrated in a cohort of 27,972 patients with type 2 diabetes mellitus (T2DM) that previous treatment with sodium-glucose cotransporter 2 (SGLT-2) inhibitors compared with dipeptidyl peptidase-4 (DPP-4) inhibitors resulted in a significant decrease in the risk for admission to ICU by 21%, for all-cause death by 56% and for death due to infections by 74%, besides the established and well-known reductions in the risk for cardiovascular and renal death. This analysis extends the results of another, recently published retrospective analysis by Wu et al (2), who demonstrated in a similarly large cohort of patients with T2DM that SGLT-2 inhibitors compared with DPP-4 inhibitors result in a significant decrease in the risk for incident sepsis by 48%, for pneumonia by 37%, for sepsis-related death by 61%, and for infection-related death by 57%.…”

Section: To the Editorsupporting

confidence: 85%

“…Pauline Yeung Ng, MBBS, FHKCP 1,2 Andrew Kei-Yan Ng, MBBS, FHKCP 3 April Ip, MPH 1 Kai-Hang Yiu, MD, PhD 3,4 The authors reply: W e would like to thank Patoulias (1) for his positive response to our article (2) recently published in Critical Care Medicine, where we showed that the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with diabetes reduced the risk of critical illness, all-cause mortality, and mortality due to sepsis.…”

mentioning

confidence: 99%

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Sodium-Glucose Cotransporter 2 Inhibitors Decrease the Risk of Acute, Severe Illness: Has the Time Come to Administer Them in the Acute Setting?

Patoulias

2023

Critical Care Medicine

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Section: To the Editorsupporting

confidence: 85%

mentioning

confidence: 99%

Sodium-Glucose Cotransporter 2 Inhibitors Decrease the Risk of Acute, Severe Illness: Has the Time Come to Administer Them in the Acute Setting?

Patoulias

2023

Critical Care Medicine

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“…19 The time-weighted lipid and glucose profiles were also calculated by the products of the sums of two consecutive measurements and the time interval, then divided by the total time interval, as suggested previously. 20…”

Section: Methodsmentioning

confidence: 99%

Comparisons of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9I) versus Ezetimibe on Major Adverse Cardiovascular Events Amongst Patients with Dyslipidaemia: A Population-Based Study

Chou,

Li,

Chung

et al. 2023

Preprint

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Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9I) have potential benefits against cardiovascular disease. The comparative risks of new-onset major adverse cardiovascular events (MACE) between PCSK9I and ezetimibe remain unknown. Objective: This real-world study compared the risks of MACE upon exposure to PCSK9I and ezetimibe. Methods: This was a retrospective population-based cohort study of patients with dyslipidaemia on either PCSK9I or ezetimibe between 1st January 2015 and 30th October 2022 using a territory-wide database from Hong Kong. The primary outcome was new-onset MACE. The secondary outcomes were myocardial infarction, heart failure, stroke/transient ischaemic attack, and all-cause mortality. Propensity score matching (1:3 ratio) using the nearest neighbour search was performed. Multivariable Cox regression was used to identify significant associations. Results: This cohort included 42450 dyslipidaemia patients (median age: 65.0 years old [SD: 11.1]; 64.54 % males). The PCSK9I and ezetimibe groups consisted of 1477 and 40973 patients, respectively. After matching, 67 and 235 patients suffered from MACE in the PCSK9I and ezetimibe groups, respectively, over a total of 14514.5 person-years. PCSK9I was associated with lower risks of MACE (Hazard ratio [HR]: 0.59; 95% Confidence Interval [CI]: 0.37-0.92) compared to ezetimibe use after adjusting for demographics, past comorbidities, other medications, and time-weighted means of lipid and glucose tests. Besides, while both alirocumab and evolocumab were associated with lower risks of MACE, evolocumab was associated with significantly lower risks of myocardial infarction, heart failure, and stroke/transient ischaemic attack. The results remained consistent in the competing risk and sensitivity analyses. Conclusions: PCSK9I use amongst dyslipidaemia patients was associated with lower risks of new-onset MACE and outcomes compared to ezetimibe after adjustments. Evolocumab might perform better than Alirocumab in reducing the risks of cardiovascular diseases.

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“…Finally, the use of SGLT-2i is associated with an increased incidence of genitourinary infections, commonly attributed to their glycosuric effect [ 113 ]. However, preliminary evidence suggests that the incidence or the outcomes linked to other infectious diseases such as pneumonia might be decreased by the use of SGLT-2i [ 114 ], an observation that might reflect their benefit on the aging immune system, but that requires additional knowledge. Finally, more data relative to the effect of these drugs in men vs. women should be thoroughly explored, given the preliminary evidence from mice studies and human patients with COVID-19 showing a putative, selective benefit for the male sex.…”

Section: Concluding Remarks and Future Prospectsmentioning

confidence: 99%

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms

Grotta

Frigé

Matacchione

et al. 2022

IJMS

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Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.

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Risk of sepsis and pneumonia in patients initiated on SGLT2 inhibitors and DPP-4 inhibitors

Cited by 22 publications

References 41 publications

Sodium-Glucose Cotransporter 2 Inhibitors Decrease the Risk of Acute, Severe Illness: Has the Time Come to Administer Them in the Acute Setting?

Sodium-Glucose Cotransporter 2 Inhibitors Decrease the Risk of Acute, Severe Illness: Has the Time Come to Administer Them in the Acute Setting?

Comparisons of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9I) versus Ezetimibe on Major Adverse Cardiovascular Events Amongst Patients with Dyslipidaemia: A Population-Based Study

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms

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