Peptidase-4 Inhibitor Use Research Articles

Association between dipeptidyl peptidase-4 inhibitor use and risk of Parkinson's disease among patients with diabetes mellitus: a retrospective cohort study.

How a person's Parkinson disease (PD) risk is affected by dipeptidyl peptidase-4 (DPP-4) inhibitors remains unclear. We evaluated the association of PD risk with use of these inhibitors in individuals diagnosed as having diabetes mellitus (DM). Individuals diagnosed as having new-onset DM were enrolled into the case group and comparison group, comprising patients who received a DPP-4 inhibitor and a sulfonylurea, respectively. These groups were matched through propensity score matching on the basis of income level, gender, urbanization level, enrollment year, age, and diabetes complications severity index score. The case group was divided into subgroups on the basis of whether they had a cumulative defined daily dose (cDDD) of <75, 75-150, or >150. The DPP-4 inhibitor-PD risk association was evaluated through a Cox proportional hazards model. The Bonferroni adjustment test was employed to adjust P-values and reduce the false positive rate. Compared with those in the comparison group (treatment with a sulfonylurea), patients with a DPP-4 inhibitor cDDD of >150 had a hazard ratio (HR) of 1.30 for PD development (95% confidence interval [CI]: 0.97-1.73; adjusted P = .263); the HRs for patients with a cDDD of <75 or 75-150 were 0.95 (95% CI: 0.71-1.27; adjusted P = .886) and 1.06 (95% CI: 0.75-1.50; adjusted P = .886), respectively. We noted nonsignificant differences regarding the associations between the use of the various DPP-4 inhibitors (linagliptin, saxagliptin, sitagliptin, and vildagliptin) and PD risk after adjustment for any individual inhibitor (adjusted P > .05). DPP-4 inhibitors were discovered in this study to not be associated with increased PD risk. This result was confirmed when the analysis was conducted individually for the 4 investigated DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and vildagliptin).

Association between dipeptidyl peptidase-4 inhibitor use and diabetic retinopathy: a systematic review and meta-analysis of real-world studies

BackgroundThe purpose of this review was to examine if dipeptidyl peptidase-4 inhibitor (DPP4i) use affects the risk of diabetic retinopathy (DR).MethodsCohort studies published up to 20th July 2023 in the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science were searched. The adjusted effect size was pooled to calculate the odds ratio (OR).ResultsSeven studies were included. Meta-analysis showed that the use of DPP4i was not associated with any significant change in the risk of DR (OR: 0.86 95% CI: 0.70, 1.06 I2 = 78%). The pooled analysis also found that DPP4i use was not associated with any significant risk of progression of DR (OR: 0.87 95% CI: 0.47, 1.59 I2 = 86%). The results did not change during sensitivity analysis.ConclusionPresent evidence from a limited number of real-world studies shows that DPP4i may not affect the incidence and progression of DR. There is a need for further studies from different countries using accurate definitions of DR and its progression to validate the current results.

Sodium-glucose cotransporter-2 inhibitors and incidence of atrial fibrillation in older adults with type 2 diabetes: a retrospective cohort analysis

ObjectivesTo investigate the risk of atrial fibrillation (AF) with sodium-glucose cotransporter-2 inhibitors (SGLT2is) compared to dipeptidyl peptidase-4 inhibitor (DPP4i) use in older US adults and across diverse subgroups.MethodsWe conducted a retrospective cohort analysis using claims data from 15% random samples of Medicare fee-for-service beneficiaries. Patients were adults with type 2 diabetes (T2D), no preexisting AF, and were newly initiated on SGLT2i or DPP4i. The outcome was the first incident AF. Inverse probability treatment weighting (IPTW) was used to balance the baseline covariates between the treatment groups including sociodemographics, comorbidities, and co-medications. Cox regression models were used to assess the effect of SGLT2i compared to DPP4i on incident AF.ResultsOf the 97,436 eligible individuals (mean age 71.2 ± 9.8 years, 54.6% women), 1.01% (n = 983) had incident AF over a median follow-up of 361 days. The adjusted incidence rate was 8.39 (95% CI: 6.67–9.99) and 11.70 (95% CI: 10.9–12.55) per 1,000 person-years in the SGLT2i and DPP4i groups, respectively. SGLT2is were associated with a significantly lower risk of incident AF (HR 0.73; 95% CI, 0.57 to 0.91; p = 0.01) than DPP4is. The risk reduction of incident AF was significant in non-Hispanic White individuals and subgroups with existing atherosclerotic cardiovascular diseases and chronic kidney disease.ConclusionCompared to the use of DPP4i, that of SGLT2i was associated with a lower risk of AF in patients with T2D. Our findings contribute to the real-world evidence regarding the effectiveness of SGLT2i in preventing AF and support a tailored therapeutic approach to optimize treatment selection based on individual characteristics.

National trends in utilisation of glucose lowering medicines by older people with diabetes in long-term care facilities

AimsTo examine national trends in glucose lowering medicine (GLM) use among older people with diabetes in long-term care facilities (LTCFs) during 2009–2019. MethodsA repeated cross-sectional study of individuals ≥65 years with diabetes in Australian LTCFs (n = 140,322) was conducted. Annual age-sex standardised prevalence of GLM use and number of defined daily doses (DDDs)/1000 resident-days were estimated. Multivariable Poisson or Negative binomial regression models were used to estimate adjusted rate ratios (aRRs) and 95 % confidence intervals (CIs). ResultsPrevalence of GLM use remained steady between 2009 (63.9%, 95 %CI 63.3–64.4) and 2019 (64.3%, 95 %CI 63.9–64.8) (aRR 1.00, 95 %CI 1.00–1.00). The percentage of residents receiving metformin increased from 36.0% (95 %CI 35.3–36.7) to 43.5% (95 %CI 42.9–44.1) (aRR 1.01, 95 %CI 1.01–1.01). Insulin use also increased from 21.5% (95 %CI 21.0–22.0) to 27.0% (95 %CI 26.5–27.5) (aRR 1.02, 95 %CI 1.02–1.02). Dipeptidyl peptidase-4 inhibitor use increased from 1.0% (95 %CI 0.9–1.1) to 21.1% (95 %CI 20.7–21.5) (aRR 1.24, 95 %CI 1.24–1.25), while sulfonylurea use decreased from 34.4% (95 %CI 33.8–35.1) to 19.3% (95 %CI 18.9–19.7) (aRR 0.93, 95 %CI 0.93–0.94). Similar trends were observed in DDDs/1000 resident days. ConclusionsThe increasing use of insulin and ongoing use of sulfonylureas suggests a need to implement evidence-based strategies to optimise diabetes care in LTCFs.

Association Between Dipeptidyl Peptidase-4 Inhibitor Use and Cognitive Functions, Brain-Derived Neurotrophic Factor, and Pentraxin-3 Levels in Patients With Type 2 Diabetes.

Background Diabetes mellitus is an important risk factor for dementia, Alzheimer's disease, and other neurodegenerative diseases. Recent findings have made the relationship between the inhibition of the dipeptidyl peptidase-4 (DPP-4) enzyme and cognitive functions an important research topic. Objective This study aimed to evaluate the association between DPP-4 inhibitor use and cognitive functions, serum brain-derived neurotrophic factor (BDNF), and pentraxin-3 (PTX-3) levels in patients with type 2 diabetes, compared with the patients who only use metformin treatment. Design, patients, and methods A total of 50 patients with type 2 diabetes (hemoglobin A1c levels at ≤%7.5) who were under treatment with metformin±DPP-4 inhibitor (n=25) or only metformin (n=25) were included in this cross-sectional study. Serum BDNF and PTX-3 levels were assessed using an enzyme-linked immunosorbent assay.A standardized mini-mental test (sMMSE) was used to evaluate cognitive functions. Results There were no significant differences in the characteristics of the study groups. The mean sMMSE score of the patients receiving DPP-4±metformin treatment was statistically higher when compared with patients receiving only metformin treatment (27.16±1.95 vs. 25.40±3.07; p=0.041). The BDNF levels of the patients receiving DPP-4±metformin treatment were considerably higher than the patients receiving only metformin treatment (394.51±205.66 ng/ml vs. 180.63±297.94 ng/ml; p=0.001). The difference in PTX-3 levels between study groups was not statistically significant (5.47±3.44 vs. 3.79±2.53; p=0.055). Conclusion When compared to metformin alone, the use of DPP-4 inhibitors in the treatment of patients with type 2 diabetes was associated with increased serum BDNF levels and improved cognitive functions.

The associations of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors as add-on to metformin with fracture risk in patients with type 2 diabetes mellitus.

To investigate whether sodium-glucose cotransporter-2 (SGLT2) inhibitor use as compared to dipeptidyl peptidase-4 (DPP-4) inhibitor use as add-on to metformin is associated with the risk of any fracture or major osteoporotic fractures (MOFs). A cohort study using the Clinical Practice Research Datalink (CPRD) Aurum database was conducted. All patients aged 18 years and older with a first-ever prescription for a DPP-4 inhibitor or an SGLT2 inhibitor as add-on to metformin between January 1, 2013 and June 30, 2020 were selected. Patients starting with SGLT2 inhibitors were matched (up to 1:3) on propensity scores to patients starting with DPP-4 inhibitors. Propensity scores were calculated based on sex, age, body mass index, comorbidities, comedication and lifestyle factors. Cox proportional hazard models were used to estimate the risk of fracture with SGLT2 inhibitor use as compared to DPP-4 inhibitor use. A total of 13 807 SGLT2 inhibitor users (age 55.4 ± 10.6 years, 36.7% female) were included in this study, matched with 28 524 DPP-4 inhibitor users (age 55.4 ± 8.0 years, 36.4% female). The risk of any fracture with current SGLT2 inhibitor use was similar compared with current DPP-4 inhibitor use (adjusted hazard ratio [aHR] 1.09, 95% confidence interval [CI] 0.91-1.31), as was the risk of MOFs (aHR 0.89, 95% CI 0.64-1.22) and the risk of fractures at any of the individual MOF sites. Additionally, no association was found with duration of SGLT2 inhibitor use (longest duration >811 days) for any of the individual SGLT2 inhibitor agents, or after stratification by sex and age. Use of SGLT2 inhibitors was not associated with the risk of any fracture, MOFs or fracture at the individual MOF sites when compared to DPP-4 inhibitor use.

Do oral antidiabetic medications alter the risk of Parkinson's disease? An updated systematic review and meta-analysis.

Diabetes mellitus is a known risk factor for Parkinson's disease (PD), but does this risk vary with antidiabetic medications is still unclear. This meta-analysis aims to compile evidence from the literature to assess the risk of idiopathic PD with various oral antidiabetic medications. Databases PubMed, CENTRAL, Scopus, Web of Science, and Embase were searched till 5th April 2023. Adjusted outcomes were pooled to generate a hazard ratio (HR) on the risk of PD with different antidiabetic medications. Fifteen studies with 2,910,405 diabetic patients were eligible. Pooled analysis failed to show any significant difference in the risk of PD among users of metformin (HR: 1.05 95% CI: 0.91, 1.22 I2 = 81%), glitazones (HR: 0.84 95% CI: 0.68, 1.05 I2 = 91%), glucagon-like peptide-1 agonists (HR: 0.63 95% CI: 0.26, 1.55 I2 = 33%), and sulfonylureas (HR: 1.13 95% CI: 0.96, 1.32 I2 = 76%). However, a meta-analysis of four studies showed that dipeptidyl peptidase-4 inhibitor use was associated with reduced risk of PD in diabetics (HR: 0.69 95% CI: 0.56, 0.86 I2 = 46%). Insufficient data was available on sodium-glucose cotransporter-2 inhibitors, α-glucosidase inhibitors, and glinides. Limited retrospective evidence indicates that DPP4i may reduce the risk of idiopathic PD in diabetics. Metformin, sulfonylureas, glucagon-like peptide-1 agonists, and glitazones were not associated with any change in the risk of PD. Further studies taking into confounding factors and using a common comparator group are needed to strengthen present evidence.

Association of sulfonylureas with the risk of dementia: A population-based cohort study.

Sulfonylureas are oral glucose-lowering medications positioned as a second-line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase-4 (DPP4) inhibitor use. Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population-based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity-score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention-to-treat exposure definition. A separate propensity-score weighted analysis was conducted to explore within-class differences in dementia risk among sulfonylurea new users selected from the primary cohort. Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person-years; aHR [95% CI] = 1.09 [1.04-1.15]) over a mean follow-up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03-1.32]). New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes.

Prevalence of diabetes mellitus in bullous pemphigoid patients in the absence of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis.

Bullous pemphigoid (BP) has been associated with dipeptidyl peptidase-4 inhibitor (DDP-4i) use in patients with diabetes mellitus (DM). The prevalence and association of DM in BP patients independent of DPP-4i use has not been investigated by meta-analysis. To perform a systematic review and meta-analysis on the association between diabetes and bullous pemphigoid. The goal was to determine the prevalence and pooled odds ratio of BP patients with DM in the absence of DDP-4i use compared to the general population prevalence of diabetes mellitus. OVID Medline, EMBASE, Cochrane Central and Web of Science were searched for relevant studies published from inception to April 2020. Case-control, case-series, cohort, and cross-sectional studies that included the association of BP and DM without DDP-4i's, in any language. PRISMA guidelines were followed for data extraction and the Newcastle-Ottawa Scale for risk of bias evaluation. Three reviewers independently performed data extraction. Pooled odds ratio and prevalence were calculated using the random effects model. The odds ratio and prevalence of BP patients with DM. Overall, 8 studies out of 856 identified publications through data base searches were included. The pooled prevalence of diabetes in patients with BP was 20.0% [95% CI 14%-26%; p = 0.00]. Within the comparative non-BP control population, 13% had diabetes. BP patients were more likely to have diabetes compared to a control population without BP [OR 2.10, 95% CI 1.22-3.60; p = 0.01]. This study found that twice the number of BP patients have DM (20%) compared to the general population reported as 10.5%, warranting monitoring of blood glucose levels in BP patients who may have yet undeclared or undiagnosed DM when initiating systemic steroids.

Noninsulin-based antihyperglycemic medications in patients with diabetes and COVID-19: A systematic review and meta-analysis.

Patients with diabetes are more likely to suffer COVID-19 complications. Using noninsulin antihyperglycemic medications (AGMs) during COVID-19 infection has proved challenging. In this study, we evaluate different noninsulin AGMs in patients with COVID-19. We searched Medline, Embase, Web of Science, and Cochrane on 24 January 2022. We used the following keywords (COVID-19) AND (diabetes mellitus) AND (antihyperglycemic agent). The inclusion criteria were studies reporting one or more of the outcomes. We excluded non-English articles, case reports, and literature reviews. Study outcomes were mortality, hospitalization, and intensive care unit (ICU) admission. The use of metformin rather than other glucose-lowering medications was associated with statistically significant lower mortality (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.47, 0.77, p< .001). Dipeptidyl peptidase-4 inhibitor (DPP-4i) use was associated with statistically significantly higher hospitalization risk (RR: 1.44, 95% CI: 1.23, 1.68, p< .001) and higher risk of ICU admissions and/or mechanical ventilation vs nonusers (RR: 1.24, 95% CI: 1.04, 1.48, p< .02). There was a statistically significant decrease in hospitalization for SGLT-2i users vs nonusers (RR: 0.89, 95% CI: 0.84-0.95, p< .001). Glucagon-like peptide-1 receptor agonist (GLP-1RA) use was associated with a statistically significant decrease in mortality (RR: 0.56, 95% CI: 0.42, 073, p< 0.001), ICU admission, and/or mechanical ventilation (RR: 0.79, 95% CI: 0.69-0.89, p< .001), and hospitalization (RR: 0.73, 95% CI: 0.54, 0.98, p= .04). AGM use was not associated with increased mortality. However, metformin and GLP-1RA use reduced mortality risk statistically significantly. DPP-4i use was associated with a statistically significant increase in the risk of hospitalization and admission to the ICU.

Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong

Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. This study included 30 385 patients. The propensity score-matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted.

Inverse association between DPP-4 inhibitor use and fracture in older adults: A disproportionality analysis ofthe FAERS and JADER.

Fractures are significantly associated with increased morbidity and mortality in older individuals; additionally, patients with diabetes mellitus are highly prone to fractures. The aim of the present study was to examine the association between dipeptidyl peptidase-4 (DPP-4) inhibitor use and the risk of fracture in older patients by analyzing data obtained from spontaneous adverse event reporting databases from the United States and Japan. Data on older patients registered in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2013 to the end of 2019 and data registered in the Japanese Adverse Drug Event Report database (JADER) from April 2004 to December 2019 were used. Reporting odds ratio (ROR) and information component (IC) values were used for disproportionality analysis. Significant inverse associations between DPP-4 inhibitor use and fracture were found for DPP-4 inhibitors as a whole (ROR = 0.80; 95% CI = 0.73-0.88; IC = -0.31, 95% CI = -0.46 to -0.17); linagliptin (ROR = 0.74; 95% CI = 0.59-0.94; IC = -0.42, 95% CI = -0.75 to -0.08); and sitagliptin (ROR = 0.77; 95% CI = 0.68-0.88; IC = -0.36, 95% CI = -0.55 to -0.17) in the analyses of FAERS data. Similarly, significant inverse associations were also found for DPP-4 inhibitors as whole (ROR = 0.71; 95% CI = 0.59 to 0.86; IC = -0.46, 95% CI = -0.74 to -0.18); sitagliptin (ROR = 0.70; 95% CI = 0.52-0.95; IC = -0.49, 95% CI = -0.93 to -0.05); and vildagliptin (ROR = 0.54; 95% CI = 0.35-0.83; IC = -0.85, 95% CI = -1.49 to -0.22) in the analyses of JADER data. Our analysis of adverse event databases using different algorithms revealed that DPP-4 inhibitor use was inversely associated with fracture in older patients.

Association of dipeptidyl peptidase-4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan.

This study was designed and carried out to investigate the association of dipeptidyl peptidase-4 inhibitor (DPP-4i) use with pancreatic cancer (PC) in individuals with diabetes in Japan. The JMDC Claims Database, which contains the medical and prescription information of Japanese employment-based health insurance programs, was used. The primary outcome was duration to the first occurrence of PC (International Classification of Diseases 10th Revision code C25), both all and hospitalized, from prescription of DPP-4is or other oral glucose-lowering agents (GLAs). Individuals with diabetes who received DPP-4is (n= 61,430) or other oral GLAs (n= 83,304) were analyzed. Follow-up periods (median [interquartile range]) were 17 months (8-33) for DPP-4is and 14 months (7-28) for other oral GLAs. Kaplan-Meier curve analysis to determine the duration of first use of DPP4i or other oral GLA to diagnosis of PC disclosed no differences between the two groups in duration to all or hospitalized PC (log-rank test: all, P= 0.7140; hospitalized, P= 0.3446). Cox proportional hazards models showed that use of DPP-4is did not affect the PC risk adjusted for medications, age, sex and risk comorbidities (all, hazard ratio 1.1, 95% confidence interval 0.8-1.3, P= 0.6518; hospitalized, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P= 0.6662). Similar results were obtained when individuals with ≥2 years oral GLA treatment and those with medical checkup data (e.g., smoking or drinking habit) available were analyzed. This database study shows that there is not a significant PC risk due to DPP-4i treatment in individuals with diabetes in Japan, but larger studies with longer follow up are required to confirm these findings.

Trends in Prescribing Preferences for Antidiabetic Medications Among Patients With Type 2 Diabetes in the U.K. With and Without Chronic Kidney Disease, 2006-2020.

To evaluate trends in antidiabetic medication initiation patterns among patients with type 2 diabetes mellitus (T2DM) with and without chronic kidney disease (CKD). A retrospective cohort study using the UK Clinical Practice Research Datalink (2006-2020) was conducted to evaluate the overall, first-, and second line (after metformin) medication initiation patterns among patients with CKD (n = 38,622) and those without CKD (n = 230,963) who had T2DM. Relative to other glucose-lowering therapies, metformin initiations declined overall but remained the first-line treatment of choice for both patients with and those without CKD. Sodium-glucose cotransporter-2 (SGLT2i) use increased modestly among patients with CKD, but this increase was more pronounced among patients without CKD; by 2020, patients without CKD, compared with patients with CKD, were three (28.5% vs. 9.4%) and six (46.3% vs. 7.9%) times more likely to initiate SGLT2i overall and as second-line therapy, respectively. Glucagon-like peptide 1 receptor agonist (GLP-1RA) use was minimal regardless of CKD status (<5%), whereas both dipeptidyl peptidase-4 inhibitor (DPP4i) and sulfonylurea use remained high among patients with CKD. For instance, by 2020, and among patients with CKD, DPP4i and sulfonylureas constituted 28.3% and 20.6% of all initiations, and 57.4% and 30.3% of second-line initiations, respectively. SGLT2i use increased among patients with T2DM, but this increase was largely driven by patients without CKD. Work is needed to identify barriers associated with the uptake of therapies with proven cardiorenal benefits (e.g., SGLT2i, GLP-1RA) among patients with CKD.

Changes over time in the cardiovascular risk profile of type 2 diabetes from 2007 to 2020: A community-based study.

To quantify changes over time in cardiovascular (CV) risk factor control and in the uptake of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors from 2007 to 2020 in a real-world community-based cohort of type 2 diabetes (T2D) patients. This study identified 95 461 T2D patients, who were followed for an average of 6.4 years through a single healthcare organization's electronic health record. The primary outcome was global risk factor control according to four factors ("ABCS"): glycated haemoglobin (HbA1c [<8%]); Blood pressure (systolic/diastolic <140/90 mmHg); Cholesterol (non-HDL cholesterol <130 mg/dL); and Smoking (not). Concomitant presence of microvascular complications and commonly used medication classes were tracked. According to the ABCS metric, global risk factor control did not appreciably change over time; in 2020, 40.9% (95% confidence interval 40.2, 41.5) of patients had all four factors controlled. Among individual components, HbA1c control (<8%) worsened over time from 84% in 2007 to 78% in 2020, while lipid control (non-HDL cholesterol <130 mg/dL) improved from 59% to 72%. Coexisting microvascular complications were more prevalent over time; for example, neuropathy prevalence increased from 21% (2007) to 35% (2020). Use of thiazolidinediones and sulphonylureas decreased over time while metformin, insulin, dipeptidyl peptidase-4 inhibitor, GLP-1RA and SGLT2 inhibitor use increased. In 2020, GLP-1RAs and SGLT2 inhibitors were each used by 13% of T2D patients. In this community-based study, global CV risk factor control in T2D did not improve, although glycaemic control worsened and lipid control improved. Given increased uptake of GLP-1RAs and SGLT2 inhibitors, the collective effect of these changes on CV outcomes warrants evaluation.

Does diabetes increase the risk of cardiovascular events in patients with negative treadmill stress echocardiography?

Cardiovascular morbidity and mortality rates are considered to be high in patients with diabetes despite negative stress test results; however, little data are available to support this supposition. We compared the long-term cardiovascular events between patients with diabetes and those without diabetes with negative treadmill stress echocardiography and evaluated the predictors for cardiovascular events in patients with diabetes. A total of 1,243 consecutive patients (mean age, 56 ± 10 years; non-diabetics: diabetics, 975:268; mean follow-up of 5 years) with negative treadmill stress echocardiography were evaluated. Clinical data were examined, and major adverse cardiovascular events (MACEs, a composite of coronary revascularization, acute myocardial infarction, and cardiovascular death) were compared between the non-diabetic and diabetic groups. In the population matched by clinical characteristics, the diabetic and non-diabetic groups had similar occurrence of MACEs (non-diabetics vs. diabetics = 5% versus 7%; p = 0.329) and event-free survival. MACEs in the diabetic group were associated with elevated early diastolic velocity of the mitral inflow/mitral annulus (E/e') ratio, indicative of diastolic dysfunction. The absence of statin and dipeptidyl peptidase-4 inhibitor use and use of sulfonylureas were also predictors of more MACEs. In conclusion, long-term cardiovascular events in patients with diabetes and negative stress echocardiography were comparable to those in patients without diabetes. However, appropriate monitoring of diastolic dysfunction, statin use, and individualized antidiabetic drug selection are required to reduce the cardiovascular risk in patients with diabetes.

Association of dipeptidyl peptidase-4 inhibitor use and the risk of asthma development among type 2 diabetes patients.

Numerous studies have shown that dipeptidyl peptidase-4 inhibitors (DPP-4i) may regulate immunological pathways implicated in asthma. The association between DPP-4i use and risk of asthma development is limited, however. We aimed to evaluate if DPP-4i treatment in individuals with type 2 diabetes mellitus (T2DM) is associated with a lower risk and severity of asthma. We performed a population-based retrospective cohort study using the Longitudinal National Health Insurance Research database between 2008 and 2015. After one-to-four propensity score matching from 1,914,201 patients with defined criteria, we enrolled 3001 patients who were on DPP-4i (DPP-4i group) for a diagnosis of T2DM but without a diagnosis of asthma for further analysis. Cox proportional hazards regression analysis was performed to estimate and compare the risk of developing and severity of asthma, including no acute exacerbations event (No-AE), acute exacerbations (AEs), status asthmaticus (Status), and required endotracheal intubation (ET-tube intubated), between the two groups. The participants had a mean age of 66.05 ± 17.23 years and the mean follow-up time was 4.96 ± 4.39 years. The risk of asthma development was significantly lower in the DPP-4i group than in the non-DPP-4i group [adjusted hazard ratio (HR) = 0.65; 95% confidence interval (CI) = 0.29-0.83; p < 0.001], with a class effect. This trend was observed for severity of asthma as No-AE (HR = 0.55; 95% CI = 0.24-0.70; p < 0.001), AE (HR = 0.57; 95% CI = 0.26-0.73; p < 0.001), and Status (HR = 0.78; 95% CI = 0.35-0.99; p = 0.047), but not in ET-tube intubated cases (HR = 0.96; 95% CI = 0.43-1.22; p = 0.258). The use of DPP-4i decreased the risk and severity of asthma with a class effect among No-AE, AE, status of asthma events, but not in ET-tube intubated events. Our report suggests that DPP-4i may play a role in attenuating the impact of asthma on incidence in the future and on more severe forms of disease exacerbation in T2DM patients.

SARS-CoV-2 and diabetes: A potential therapeutic effect of dipeptidyl peptidase 4 inhibitors in diabetic patients diagnosed with COVID-19

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 and has become an urgent economic and health challenge. Dipeptidyl peptidase 4 (DPP4), also mentioned as a cluster of differentiation 26 (CD26) is a serine exopeptidase found in two arrangements: a soluble form (sDPP-4) and a plasma membrane-bound form. Because other coronaviruses enter the cells by binding to DPP-4, it has been speculated that DPP-4 inhibitors may exert activity against COVID-19. Therefore, this review aimed to summarize the potential therapeutic effect of dipeptidyl peptidase 4 inhibitors in diabetic patients diagnosed with COVID-19. To include different studies, publications related to Dipeptidyl peptidase-4 inhibitor use and clinical outcomes from COVID-19 were searched from the databases such as Web of Science, PubMed, Medline, Elsevier, Google Scholar, and SCOPUS, via English key terms. A direct engrossment of DPP4 in COVID-19 needs to be elucidated, there is also evidence confirming that DPP4 inhibitors exert anti-fibrotic and modulate inflammation activity. Thus, the use of DPP-4 inhibitors could reduce mortality due to COVID-19 or improve the progression of COVID-19; this evidence may support the management of diabetic patients diagnosed with COVID-19; however more well-designed investigation is urgently required.

Dipeptidyl peptidase-4 inhibitor use is associated with a lower erythrocyte sedimentation rate in patients with remitting seronegative symmetrical synovitis with pitting oedema and pre-existing diabetes mellitus.

Dipeptidyl peptidase-4 inhibitor use is associated with a lower erythrocyte sedimentation rate in patients with remitting seronegative symmetrical synovitis with pitting oedema and pre-existing diabetes mellitus.

Association of Dipeptidyl Peptidase-4 Inhibitor Use and Amyloid Burden in Patients With Diabetes and AD-Related Cognitive Impairment.

To investigate whether dipeptidyl peptidase-4 inhibitors (DPP-4i) have beneficial effects on amyloid aggregation and longitudinal cognitive outcome in diabetic Alzheimer disease-related cognitive impairment (ADCI). We retrospectively reviewed 282 patients with ADCI with positive 18F-florbetaben amyloid PET images. Patients were classified into 3 groups according to prior diagnosis of diabetes and DPP-4i use: diabetic patients being treated with (ADCI-DPP-4i+, n = 70) or without DPP-4i (ADCI-DPP-4i-, n = 71) and nondiabetic patients (n = 141). Multiple linear regression analyses were performed to determine intergroup differences in global and regional amyloid retention using standardized uptake value ratios calculated from cortical areas. We assessed longitudinal changes in Mini-Mental State Examination (MMSE) score using a linear mixed model. The ADCI-DPP-4i+ group had lower global amyloid burden than the ADCI-DPP-4i- group (β = 0.075, SE = 0.024, p = 0.002) and the nondiabetic ADCI group (β = 0.054, SE = 0.021, p = 0.010) after adjusting for age, sex, education, cognitive status, and APOE ε4 carrier status. The ADCI-DPP-4i+ group had lower regional amyloid burden in temporo-parietal areas than either the ADCI-DPP-4i- group or the nondiabetic ADCI group. The ADCI-DPP-4i+ group showed a slower longitudinal decrease in MMSE score (β = 0.772, SE = 0.272, p = 0.005) and memory recall subscore (β = 0.291, SE = 0.116, p = 0.012) than the ADCI-DPP-4i- group. These findings suggest that DPP-4i use is associated with low amyloid burden and favorable long-term cognitive outcome in diabetic patients with ADCI.