Exposure to dipeptidyl‐peptidase 4 inhibitors and the risk of pneumonia among people with type 2 diabetes: Retrospective cohort study and meta‐analysis

Morieri, Mario Luca; Bonora, Benedetta Maria; Longato, Enrico; Camilo, Barbara Di; Sparacino, Giovanni; Tramontan, Lara; Avogaro, Angelo; Fadini, Gian Paolo

doi:10.1111/dom.14142

Cited by 13 publications

(10 citation statements)

References 31 publications

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“…34 Second, it is also possible that the observed protective association is the result of an increased risk of pneumonia with DPP-4i. However, although there may be a biological mechanism linking DPP-4i to an increased risk of infections, [35][36][37] most previous studies of the pneumonia risk of DPP-4i did not identify an increased risk, [21][22][23][24][25]38 suggesting that this is an unlikely explanation for the observed association. Third, the observed association may be the result of residual confounding.…”

Section: Discussionmentioning

confidence: 80%

SGLT‐2 inhibitors and the risk of hospitalization for community‐acquired pneumonia: A population‐based cohort study

Brunetti

Reynier

Azoulay

et al. 2021

Pharmacoepidemiology and Drug

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Purpose: Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have been associatedwith an increased risk of genitourinary tract infections. Through similar biological mechanisms, they may also increase the risk of community-acquired pneumonia. Our objective was to compare the rate of hospitalization for community-acquired pneumonia (HCAP) with SGLT-2i compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) among patients with type 2 diabetes.Methods: We used the United Kingdom's Clinical Practice Research Datalink Gold, linked to hospitalization data, to construct a cohort of patients with type 2 diabetes.Using a time-dependent Cox proportional hazards model, we estimated the adjusted hazard ratio (HR) for HCAP with current use of SGLT-2i versus DPP-4i.Results: Among 29 896 patients, 705 HCAPs occurred over a mean follow-up of 1.7 years (SD: 1.2). Incidence rates for SGLT-2i and DPP-4i users were 6.2 (95% confidence interval [CI]: 3.7, 10.2) and 17.8 (95% CI: 15.3, 20.7) per 1000 person-years, respectively. Current use of SGLT-2i was associated with a decreased risk of HCAP compared to current use of DPP-4i (adjusted HR: 0.48, 95% CI: 0.28, 0.82). However, a comparison of SGLT-2i versus glucagon-like peptide-1 receptor agonists (GLP-1 RA) found no difference in risk of HCAP (adjusted HR: 0.94, 95% CI: 0.44, 1.89).Conclusions: SGLT-2i are associated with a decreased rate of HCAP compared to DPP-4i, but not when compared to GLP-1 RA, among patients with type 2 diabetes.Sodium-glucose co-transporter 2 inhibitors (SGLT-2i) are a novel class of glucose-lowering drugs used for the treatment of type 2 diabetes. 1In addition to their glucose lowering effects, SGLT-2i also improve cardiovascular outcomes, 2-4 which has made them increasingly prescribed in recent years. 5 However, the United States Food and Drug Administration has issued a safety warning for an increased risk of genital and urinary tract infections, 6 possibly due to increased bacterial proliferation resulting from glycosuria. Some SGLT-2i also have affinities for SGLT-1 receptors found in the lungs and intestines. 7 Inhibition of SGLT-1 receptors in rat alveolar cells leads to increased airway surface liquid glucose concentration, which translates directly to increased proliferation of pathogenic bacteria, 8 which may lead to lung infections such as community-acquired pneumonia (CAP). This mechanism may be analogous to the increased risk of

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Section: Discussionmentioning

confidence: 80%

SGLT‐2 inhibitors and the risk of hospitalization for community‐acquired pneumonia: A population‐based cohort study

Brunetti

Reynier

Azoulay

et al. 2021

Pharmacoepidemiology and Drug

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“…Using DPP4is as a comparator also avoided time-lagging bias (28) and allowed a clinically relevant comparison since both SGLT2is and DPP4is are used as second-or thirdline anti-diabetic treatment. There was also no significant association between DPP4is and pneumonia risk as reported in a recent meta-analysis of clinical trials (11). Third, a PS calculated from 67 covariates, which covered a wide range of clinically relevant conditions, would greatly reduce potential confounding.…”

Section: Strengths and Limitationsmentioning

confidence: 89%

“…DPP4is were chosen as a comparator because both SGLT2is and DPP4is were commonly used as second-or third-line anti-diabetic agents in Hong Kong, thus avoiding confounding by indication. In addition, a recent meta-analysis of clinical trials showed no association between DPP4is and the risk of pneumonia (11). Exclusion criteria were: 1) patients with the use of SGLT2is before index date for the DPP4i control group; 2) patients with DPP4i and SGLT2i initiated on the same date; 3) patients of type 1 diabetes (T1D); 4) patients with prescription records of index drugs for only 1 day; 5) patients who received dialysis or renal transplant within 1 year before index date; and 6) patients with no laboratory measurements of HbA1c or eGFR within 1 year before index date (Figure 1).…”

Section: Study Cohortmentioning

confidence: 99%

“…Population-based studies reported associations between metformin use and reduced risks of pneumonia hospitalization (8,9). However, similar effects were not reported for other classes of glucose-lowering drugs, including sulfonylurea (10), thiazolidinediones (10), and dipeptidyl peptidase-4 inhibitors (DPP4is) (11), while the association of SGLT2is with pneumonia remains largely unclear. A recent meta-analysis of 8 placebo-controlled clinical trials reported a reduced risk of pneumonia among participants treated with SGLT2is (12).…”

Section: Introductionmentioning

confidence: 99%

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Association Between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients With Type 2 Diabetes

Tan

Cheung

et al. 2021

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium-glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown. Objective To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared to dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong. Design A retrospective cohort study. The “prevalent new-user” design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the two groups. Setting and participants Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System (CDARS). Main Outcome Measures Pneumonia incidence and mortality. Results The PS-matched cohort consisted of 6,664 users of SGLT2is and 26,656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared to DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI: 2.61-5.51). The corresponding IRR was 0.71 (95% CI: 0.62-0.81). Similar reduction in risk of pneumonia death was observed (HR: 0.57; 95% CI: 0.42-0.77). Conclusion Compared to DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting.

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“…In people with diabetes, prior studies suggested a lack of an association between the use of DPP-4 inhibitors and the occurrence of community-acquired pneumopathy from any cause, 12,24 but also specifically because of SARS-CoV-2. 14 Furthermore, recent observations reported either a reduced mortality rate 25,26 or a neutral effect 27,28 associated with the use of DPP-4 inhibitors prior to or during hospitalization for COVID-19, in patients with T2D.…”

Section: Discussionmentioning

confidence: 99%

Use of dipeptidyl peptidase‐4 inhibitors and prognosis of COVID‐19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study

Roussel

Darmon

Pichelin

et al. 2021

Diabetes Obesity Metabolism

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Aim To investigate the association between routine use of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and the severity of coronavirus disease 2019 (COVID‐19) infection in patient with type 2 diabetes in a large multicentric study. Materials and Methods This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID‐19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP‐4 inhibitors users vs. non‐users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW). Results Five hundred and ninety‐six participants were under DPP‐4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non‐users of DPP‐4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW‐adjusted models showed no significant association between the use of DPP‐4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77–1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78–1.17]). Similar neutral findings were found between use of DPP‐4 inhibitors and the risk of tracheal intubation and death. Conclusions These data support the safety of DPP‐4 inhibitors for diabetes management during the COVID‐19 pandemic and they should not be discontinued.

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Exposure to dipeptidyl‐peptidase 4 inhibitors and the risk of pneumonia among people with type 2 diabetes: Retrospective cohort study and meta‐analysis

Cited by 13 publications

References 31 publications

SGLT‐2 inhibitors and the risk of hospitalization for community‐acquired pneumonia: A population‐based cohort study

SGLT‐2 inhibitors and the risk of hospitalization for community‐acquired pneumonia: A population‐based cohort study

Association Between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients With Type 2 Diabetes

Use of dipeptidyl peptidase‐4 inhibitors and prognosis of COVID‐19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study

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