Use of oral antidiabetic agents and risk of community‐acquired pneumonia: a nested case–control study

Gorricho, Javier; Garjón, Javier; Alonso, Álvaro; Celaya, María Concepción; Saiz, Luis Carlos; Erviti, Juan; López, A Beteta

doi:10.1111/bcp.13288

Cited by 46 publications

(45 citation statements)

References 25 publications

(27 reference statements)

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“…The last lane reports the final estimate for all molecules found that DPP-4 inhibitors exerted no protection against pneumonia. 28 Pooling those two literature studies with our findings led to inconclusive results, as the overall RR of pneumonia associated with DPP-4 inhibitors was not significantly different from 1.0. It is important to note that both the study by Wvan der Zanden et al 27 and the current study were cohort studies and provide essentially superimposable results, whereas the study by Gorricho et al 28 was a nested case control study.…”

Section: Discussionmentioning

confidence: 49%

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

Morieri

Bonora

Longato

et al. 2020

Diabetes Obesity Metabolism

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Aim Concerns have been raised that dipeptidyl‐peptidase 4 inhibitors (DPP‐4i) may increase the risk of pneumonia. We analysed observational data and clinical trials to explore whether use of DPP‐4i modifies the risk of pneumonia. Methods We identified patients with diabetes in the Veneto region administrative database and performed propensity score matching between new users of DPP‐4 inhibitors and new users of other oral glucose‐lowering medications (OGLMs). We compared the rate of hospitalization for pneumonia between matched cohorts using the Cox proportional hazard model. The same analysis was repeated using the database of a local diabetes outpatient clinic. We retrieved similar observational studies from the literature to perform a meta‐analysis. Results from trials reporting pneumonia rates among patients randomized to DPP‐4 inhibitors versus placebo/active comparators were also meta‐analysed. Results In the regional database, after matching 6495 patients/group, new users of DPP‐4 inhibitors had a lower rate of hospitalization for pneumonia than new users of other OGLMs (HR 0.76; 95% CI 0.61‐0.95). In the outpatient database, after matching 867 patients/group, new users of DPP‐4 inhibitors showed a non‐significantly lower rate of hospitalization for pneumonia (HR 0.65; 95% CI 0.41‐1.04). The meta‐analysis of observational studies yielded an overall non‐significant lower risk of hospitalization for pneumonia among DPP‐4 inhibitor users (RR 0.81; 95% CI 0.65‐1.01). The meta‐analysis of randomized controlled trials showed no overall effect of DPP‐4 inhibitors on pneumonia risk (RR 1.06; 95% CI 0.93‐1.20). Conclusion The use of DPP‐4 inhibitors can be considered as safe with regard to the risk of pneumonia.

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Section: Discussionmentioning

confidence: 49%

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

Morieri

Bonora

Longato

et al. 2020

Diabetes Obesity Metabolism

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“…Previous studies have raised concerns about the safety of antihyperglycemic combination therapies in relation to diabetes-related outcomes such as hypoglycemia [ 40 ], cardiovascular events and mortality [ 41 ], and microvascular complications [ 42 ]. However, recent studies have also focused on some less-known safety issues related to multiple drug use, including dementia [ 43 ], fracture risk [ 44 ], and community-acquired pneumonia [ 45 ]. Our findings suggest that undernutrition is another condition that can be found more frequently in older adults with T2DM requiring multiple antihyperglycemics.…”

Section: Discussionmentioning

confidence: 99%

Multiple Antihyperglycemic Drug Use is Associated with Undernutrition Among Older Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study

2019

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Introduction Undernutrition is prevalent in older age. Current management of type 2 diabetes mellitus (T2DM) requires modified diet patterns; however, older adults with diabetes may also be at the risk of undernutrition due to age, disease, and medication-related factors. Our objectives in this study were to examine the proportion and associations of undernutrition among community-dwelling older adults with T2DM. Methods This prospective, cross-sectional study involved older outpatient adults (≥ 65 years) with and without T2DM. We assessed the nutritional status using the Mini Nutritional Assessment-Short Form. Undernutrition referred to being either at risk of malnutrition or malnourished. Variables independently associated with undernutrition were evaluated by logistic regression analysis. Results Five hundred forty-six older adults [ n = 215 with T2DM and n = 331 control; mean (SD) age, 74.9 (6.3) years; 388 (71.1%) female] were included in the study. The frequency of undernutrition was 31.1%, which was higher in patients with T2DM than in those without (36.7% vs. 27.5%, p < 0.05). However, the difference was no longer significant after adjustment for covariates (gender, lower education, lower body mass index, cardiovascular disease, multimorbidity, cognitive performance, functional performance, depressive symptoms, and polypharmacy). In the T2DM group, the ratio of multiple antihyperglycemic drug use (≥ 2) was higher in those with undernutrition compared with normal nutritional status (78.5% vs. 59.6%, p = 0.005). On multivariable analysis, decreased functional performance, depressive symptoms, and use of multiple antihyperglycemic drugs were associated with undernutrition in patients with T2DM. Conclusions Undernutrition was more common among older adults with T2DM compared with the control group. Undernutrition was further dependent on chronic conditions and diabetes management.

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“…Prior observational studies examining the risk of DPP4 inhibitors and infections have examined all-cause infections 12 , upper respiratory tract infections 13 ,or pneumonia 18,19,48 as outcomes of interest. Similarly, the majority of meta-analysis pooling results from clinical trials suggest that there is not a significant risk of all-cause infection, upper respiratory tract infections, or pneumonia associated with using a DPP4 inhibitor.…”

Section: Discussionmentioning

confidence: 99%

“…A recently published meta-analysis pooling these trials did not find a difference in the rate of respiratory tract infections between users of DPP4 inhibitors and other agents 17 ; however, the included trials were of short duration and not designed to assess long-term safety. Recent observational studies have also failed to show any relationship between DPP4 inhibitors and community-acquired pneumonia 18,19 .…”

Section: Introductionmentioning

confidence: 99%

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas and Other Glucose-lowering Therapies for Three Acute Outcomes

Gamble

Donnan

Chibrikov

et al. 2018

Sci Rep

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Although the glucose lowering effect of dipeptidyl peptidase-4 (DPP4) inhibitors is well established, several potential serious acute safety concerns have been raised including acute kidney injury, respiratory tract infections, and acute pancreatitis. Using the UK-based Clinical Practice Research Datalink (CPRD), we identified initiators (365-day washout period) of DPP4 inhibitors and relevant comparators including initiators of sulfonylureas, metformin, thiazolidinediones, and insulin between January 2007 and January 2016 to quantify the association between DPP4 inhibitors and three acute health events – acute kidney injury, respiratory tract infections, and acute pancreatitis. The associations between drug and study outcomes were estimated using Cox proportional hazard models adjusted for deciles of high-dimensional propensity scores and number of additional glucose lowering agents. After controlling for potential confounders, the risk was not significantly increased or decreased for initiators of DPP4 inhibitors compared to sulfonylureas (hazard ratio (HR) [95% confidence interval (CI)] for acute kidney injury: 0.81 [0.56–1.18]; HR for respiratory tract infections: 0.93 [0.84–1.04]; HR for acute pancreatitis 1.03 [0.42–2.52], metformin (HR for respiratory tract infection 0.91 [0.65–1.27]), thiazolidinediones (HR for acute kidney injury: 1.12 [0.60–2.10]; HR for respiratory tract infections: 1.02 [0.86–1.21]; HR for acute pancreatitis: 1.21 [0.25–5.72]), or insulin (HR for acute kidney injury: 1.40 [0.77–2.55]; HR for respiratory tract infections: 0.74 [0.60–0.92]; HR for acute pancreatitis: 1.01 [0.24–4.19]). Initiators of DPP4 inhibitors were associated with an increased risk of acute kidney injury when compared to metformin initiators (HR [95% CI] for acute kidney injury: 1.85 [1.10–3.12], although this association was attenuated when DPP4 inhibitor monotherapy was compared to metformin monotherapy exposure as a time-dependent variable (HR 1.39 [0.91–2.11]). Initiation of a DPP4 inhibitor was not associated with an increased risk of acute kidney injury, respiratory tract infections, or acute pancreatitis compared to sulfonylureas or other glucose-lowering therapies.

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Use of oral antidiabetic agents and risk of community‐acquired pneumonia: a nested case–control study

Cited by 46 publications

References 25 publications

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

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

Multiple Antihyperglycemic Drug Use is Associated with Undernutrition Among Older Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylureas and Other Glucose-lowering Therapies for Three Acute Outcomes

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