Use Of Sitagliptin Research Articles

Assessment of cancer risk associated with 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine-contaminated sitagliptin use: A retrospective cohort study.

A recent US Food and Drug Administration report highlighted concerns over nitrosamine (7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo-[4,3-a]pyrazine [NTTP]) impurities in sitagliptin, prompting investigations into its safety profile. The present study aimed to determine if the use of NTTP-contaminated sitagliptin, in comparison with other dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with an increased cancer risk. This retrospective cohort study secondarily used the National Database of Health Insurance Claims and Specific Health Checkups of Japan, encompassing data on >120 million individuals. The study involved patients who initiated DPP-4 inhibitor therapy (sitagliptin or other DPP-4 inhibitors) and continued its exclusive use for 3 years. Sitagliptin users were compared with other DPP-4 inhibitor users for assessing the occurrence of cancers, as defined by diagnosis codes. Further analyses focused on specific types of cancer, using either diagnosis codes or a combination of diagnosis and procedure codes. We also carried out various sensitivity analyses, including those with different exposure periods. Sitagliptin users (149,120 patients, 388,356 person-years) experienced 9,643 cancer incidences (2,483.0/100,000 person-years) versus 12,621 incidences (2,504.4/100,000 person-years) among other DPP-4 inhibitor users (199,860 patients, 503,952 person-years), yielding a minimal difference (incidence rate ratio 0.99, 95% confidence interval 0.97-1.02). A multiple Cox proportional hazards model showed no significant association between sitagliptin use and overall cancer incidence (hazard ratio 1.01, 95% confidence interval 0.98-1.04). Findings were also consistent across cancer types and sensitivity analyses. We observed no evidence to suggest an increased cancer risk among patients prescribed NTTP-contaminated sitagliptin, although continued investigation is needed.

Preferences and Prescription Practices for Managing Diabetes with a Special Reference to the Clinical Use of Sitagliptin in Indian Settings

Background: Although there were several clinical studies regarding the effectiveness of sitagliptin, there were dearth of studies on the prescription patterns and practices among clinicians. Methodology: This cross-sectional study included 19 statements with multiple responses in a pretested questionnaire format to gather and understand the current prescription practices, clinical observation and preferences for managing diabetes with a special reference to the clinical use of sitagliptin in Indian settings. The survey respondents were specialists with expertise in managing diabetes. Results: According to 49% of clinicians, the preferred drug combination for managing diabetes with hemoglobin A1C (HbA1C) levels >9% is dipeptidyl peptidase 4 inhibitors (DPP4i) + metformin + glimepiride. The majority of clinicians (89.92%) recommended sitagliptin as the preferred gliptin for cardiovascular (CV) protection in diabetic patients. Approximately 38% of clinicians considered established cardiovascular outcome trials (CVOT) and CV benefits as decisive factors in prescribing sitagliptin as a first- or second-line therapy for diabetic patients. Around 72% of clinicians preferred sitagliptin + dapagliflozin as an oral antidiabetic (OAD) combination for type 2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD). Approximately 42% of respondents reported sitagliptin + metformin as the preferred OAD combination, prescribed as a single pill, for uncontrolled T2DM patients with HbA1c levels >8%. Conclusion: The study highlighted the prescription trends favoring sitagliptin-based therapies in the management of diabetes, with potential cardiovascular benefits and as first- or second-line OAD therapy. The respondents also emphasized the significance of personalized approaches, such as the sitagliptin + dapagliflozin combination, for T2DM patients with CKD.

Frequency of Mortality and Adverse Outcomes of COVID-19 in Hospitalized Type 2 Diabetics with a History of Sitagliptin or Metformin Use

Background: The relationship between various blood glucose-lowering treatments for type 2 diabetes mellitus (T2DM) and the mortality and complication rates of COVID-19 infection holds significant relevance. Objectives: This retrospective study aimed to investigate the clinical progression of COVID-19 in T2DM patients previously treated with sitagliptin, metformin, or a combination of both. Methods: The study reviewed the medical records of T2DM patients with COVID-19 who had received treatment with sitagliptin, metformin, or both. Participants were selected from those admitted to Naft Hospital in Ahvaz, Iran, from March 2020 to March 2022. Data on mortality and adverse outcomes related to COVID-19 were gathered from the medical records. Results: The study included 529 diabetic patients treated with metformin (n = 197), sitagliptin (n = 231), or both (n = 101) for a minimum of three months. The overall mortality rate among diabetic patients was 15.1%, with the metformin group showing the highest mortality rate at 28.9% (P < 0.0001). Significant differences were observed among the three treatment groups in terms of the frequency of acute respiratory failure (P < 0.0001), stroke (P = 0.002), pulmonary embolism (P < 0.0001), and the necessity for ICU admission (P < 0.0001). Nonetheless, the incidence of myocardial infarction did not significantly differ between the groups. Conclusions: The findings suggest that sitagliptin use for blood sugar control in T2DM patients may help reduce adverse outcomes and the risk of death due to COVID-19. Mortality and morbidity rates were found to be higher in patients treated with metformin compared to those in the other groups.

Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Network-based screening identifies sitagliptin as an antitumor drug targeting dendritic cells

BackgroundDendritic cell (DC)-mediated antigen presentation is essential for the priming and activation of tumor-specific T cells. However, few drugs that specifically manipulate DC functions are available. The identification of drugs...

Preclinical Repurposing of Sitagliptin as a Drug Candidate for Colorectal Cancer by Targeting CD24/CTNNB1/SOX4-Centered Signaling Hub.

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also discovered a novel population of tumor-infiltrating CD24+ cancer-associated fibroblasts (CAFs), suggesting that the CD24/SOX4-centered signaling hub could be a potential therapeutic target. Pathway networking analysis revealed a connection between the CD24/SOX4-centered signaling, β-catenin, and DPP4. Emerging evidence indicates that DPP4 plays a role in CRC initiation and progression, implicating its involvement in generating CSCs. Based on these bioinformatics data, we investigated whether sitagliptin, a DPP4 inhibitor and diabetic drug, could be repurposed to inhibit colon CSCs. Using a molecular docking approach, we demonstrated that sitagliptin targeted CD24/SOX4-centered signaling molecules with high affinity. In vitro experimental data showed that sitagliptin treatment suppressed CRC tumorigenic properties and worked in synergy with 5FU and this study thus provided preclinical evidence to support the alternative use of sitagliptin for treating CRC.

Metformin and sitagliptin fixed combination as the optimal choice in solving current problems in the type 2 diabetes mellitus treatment

The complex pathogenesis of type 2 diabetes mellitus (DM) is the basis for providing the therapeutic treatment for various disorders, which ensures a better glucose-lowering potential and maintenance of glycemic control as the disease progresses. A key reason for poor glycemic control is clinical inertia, which can be overcome by using antidiabetic fixed-dose combinations (FC). Their use improves glycemic control, as the multidirectional action of the combination components on the pathogenetic mechanisms of type 2 diabetes leads to increased pharmacological effects. The PK of metformin and sitagliptin is preferable in terms of glucose-lowering efficacy, safety and clinical benefits. The mechanism of action of metformin is not associated with the stimulation of insulin secretion by β-cells, but results from the drug’s effect on insulin sensitivity at the level of the liver, muscle and adipose tissue, although the effect on hepatic glucose production is the prevailing one. The mechanism of action of sitagliptin, a highly selective inhibitor of dipeptidyl peptidase-4, is additional to the basic pharmacological effects of metformin, which are caused by several mechanisms not associated with stimulation of insulin secretion by β-cells. The simultaneous use of sitagliptin and metformin has additive effects on the increase of glucagon-like peptide-1 levels. This action is implemented through various mechanisms, while metformin increases the release, and sitagliptin inhibits the active degradation of glucagon-like peptide-1. The article emphasizes the importance of rational combinations of glucose-lowering drugs, the need for a personalized approach to the choice of medicines. The current possibilities of sugar-reducing therapy, the issues of efficacy, safety and benefits of PK of metformin and sitagliptin are discussed using modern evidence-based data.

Unveiling the Differential Impact of Clarithromycin and Metronidazole on the Incretin Effect of Sitagliptin

Background: Sitagliptin is a commonly used drug for the treatment of type 2 diabetes. Studies show that diabetic patients are at high risk of suffering severe complications after amoebic infection. To treat these amoebic infections drugs like clarithromycin and metronidazole are most commonly indicated. Methods: Studies were conducted in normal male Wistar rats with oral doses of 10 mg/kg body weight of sitagliptin, 10 mg/kg body weight of clarithromycin &amp; 5 mg/kg body weight of metronidazole, and their combination for duration of 14 days. Blood glucose level was analyzed on weekly basis with the help of a glucometer. For measuring plasma insulin the blood was collected with heart puncture and analyzed with the help of ELISA. Result: The clarithromycin and metronidazole themselves do not have any hypoglycemic.However, when clarithromycin is used together with sitagliptin, it increases the anti-diabetic effect of sitagliptin. This means that there is drug-drug interaction between clarithromycin and sitagliptin. After evaluation of liver drug-metabolizing enzyme, it was concluded that clarithromycin inhibits the CYP3A4 enzyme which is responsible for the metabolism of sitagliptin. As a result the anti-diabetic effect of sitagliptin increases. However, together use of metronidazole and sitagliptin do not have such type of drug interactions. Conclusion: From this study it was concluded that the combined use of clarithromycin and sitagliptin may need a little dose adjustment and care should be taken when the combination is prescribed to the patient. While the combination use of metronidazole with sitagliptin has no significant effect on sitagliptin therapy.

Evaluation of the anti-diabetic drug sitagliptin as a novel attenuate to SARS-CoV-2 evidence-based in silico: molecular docking and molecular dynamics.

The online version contains supplementary material available at 10.1007/s13205-022-03406-w.

Chiral Luminescent Sensor Eu-BTB@d-Carnitine Applied in the Highly Effective Ratiometric Sensing of Curing Drugs and Biomarkers for Diabetes and Hypertension.

Chiral drugs are of great significance in drug development and life science because one pair of enantiomers has a different combination mode with target biological active sites, leading to a vast difference in physical activity. Metal-organic framework (MOF)-based chiral hybrid materials with specific chiral sites have excellent applications in the highly effective sensing of drug enantiomers. Sitagliptin and clonidine are effective curing drugs for controlling diabetes and hypertension, while insulin and norepinephrine are the biomarkers of these two diseases. Excessive use of sitagliptin and clonidine can cause side effects such as stomach pain, nausea, and headaches. Herein, through post-synthetic strategy, MOF-based chiral hybrid material Eu-BTB@d-carnitine (H3BTB = 1,3,5-benzenetrisbenzoic acid) was synthesized. Eu-BTB@d-carnitine has dual emission peaks at 417 and 616 nm when excited at 330 nm. Eu-BTB@d-carnitine can be applied in luminescent recognition toward sitagliptin and clonidine with high sensitivity and low detection limit (for sitagliptin detection, Ksv is 7.43 × 106 [M-1]; for clonidine detection, Ksv is 9.09 × 106 [M-1]; limit of detection (LOD) for sitagliptin is 10.21 nM, and LOD of clonidine is 8.34 nM). In addition, Eu-BTB@d-carnitine can further realize highly sensitive detection of insulin in human fluids with a high Ksv (2.08 × 106 [M-1]) and a low LOD (15.48 nM). On the other hand, norepinephrine also can be successfully discriminated by the hybrid luminescent platform of Eu-BTB@d-carnitine and clonidine with a high Ksv value of 4.79 × 106 [M-1] and a low LOD of 8.37 nM. As a result, the chiral hybrid material Eu-BTB@d-carnitine can be successfully applied in the highly effective ratiometric sensing of curing drugs and biomarkers for diabetes and hypertension.

Use of gliptins reduces levels of SDF-1/CXCL12 in bullous pemphigoid and type 2 diabetes, but does not increase autoantibodies against BP180 in diabetic patients.

The use of dipeptidyl peptidase 4 (DPP4) inhibitors, (also known as gliptins), is associated with an increased risk of bullous pemphigoid (BP), an autoimmune blistering skin disease. To explore the mechanism behind gliptin-associated BP we investigated circulating autoantibodies against the major BP autoantigen BP180 in serum samples from patients with type 2 diabetes (T2D) with preceding gliptin medication (n = 136) or without (n = 136). Sitagliptin was the most frequently prescribed gliptin (125/136 patients). Using an ELISA assay, we showed that IgG autoantibodies against the immunodominant NC16A domain of BP180 were found in 5.9% of gliptin treated and in 6.6% of non-gliptin treated T2D patients. We found that 28% of gliptin treated patients had IgG autoantibodies recognizing the native full-length BP180 in ELISA, but among non-gliptin treated the seropositivity was even higher, at 32%. Further ELISA analysis of additional serum samples (n = 57) found no major changes in the seropositivity against BP180 during a follow-up period of about nine years. In immunoblotting, full-length BP180 was recognized by 71% of gliptin treated and 89% of non-gliptin treated T2D patients, but only by 46% of the age-and sex-matched controls. The chemokine stromal derived factor-1(SDF-1/CXCL12) is one of the major substrates of DPP4. Immunostainings showed that the expression of SDF-1 was markedly increased in the skin of BP patients, but not affected by prior gliptin treatment. We found that the use of gliptins decreased the serum level of SDF-1α in both BP and T2D patients. Our results indicate that the autoantibodies against the linear full-length BP180 are common in patients with T2D, but seropositivity is unaffected by the use of sitagliptin.

Effects of insulin and sitagliptin on early cardiac dysfunction in diabetic rats

AimsCardiac affection is common in diabetic patients. Although insulin exerts a cardioprotective role, it may not be enough to totally prevent this affection. The current study aimed to compare the cardioprotective effect of insulin alone or combined with sitagliptin in a rat model of type 1 diabetes mellitus. Materials and methodsDiabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Diabetic rats were treated with insulin (3 IU), insulin (6 IU), or insulin (3 IU) + sitagliptin (10 mg/kg) for 42 days. Key findingsDiabetic rats exhibited significant systolic and diastolic cardiac affection with significant elevation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and brain natriuretic peptide (BNP) levels. Treatment with insulin prevented the deterioration of diabetes-induced cardiac condition, an effect that was significantly potentiated by the combined use of sitagliptin. SignificanceThe combined use of sitagliptin and insulin significantly improved the cardioprotective effect of insulin and prevented the early cardiac dysfunction in STZ diabetic rats.

The effect of select systemic medications on outcomes in diabetics with central retinal vein occlusion.

Background:Diabetes mellitus is a risk factor for central retinal vein occlusion (CRVO); however, it is unclear whether certain commonly used medications among diabetics or glycemic control impact visual outcomes in diabetic eyes with CRVO.Purpose:To evaluate the effect of select systemic medications and glycemic control on presenting features, treatment burden, and outcomes in patients with diabetes who develop a central retinal vein occlusion (CRVO).Methods:Retrospective longitudinal cohort study at a single tertiary academic referral center from 2009–2017 investigating eyes of patients being treated for diabetes mellitus at CRVO onset. Eyes with a prior history of anti-vascular endothelial growth factor (anti-VEGF) therapy or laser treatment within the year prior to CRVO onset were excluded. Main outcomes and measures were visual acuity (VA), central subfield thickness (CST), cystoid macular edema (CME), and number of intravitreal injections and laser treatment throughout follow-up.Results:We identified 138 eyes of 138 participants who were diabetic at CRVO onset. Of these, 49% had an ischemic CRVO. Median follow-up time was 25.5 months. Fifty-five eyes (40%) had a HbA1c within 6 months of CRVO presentation. HbA1c was positively correlated with both presenting CST (p = 0.04) and presence of CME (p < 0.01). In all 138 eyes, mean presenting VA was 20/246, and mean final VA was 20/364. Better-presenting VA was significantly associated with aspirin 325 mg use (p = 0.04). Lower CST at presentation was significantly associated with metformin use (p = 0.02). Sitagliptin use at CRVO onset was associated with a lower prevalence of CME at final follow-up (p < 0.01). Lower final CST was significantly associated with glipizide use at CRVO onset (p = 0.01). There were no significant associations between systemic medications or HbA1c and treatment burden or final VA (p > 0.05).Conclusion:Although aspirin 325 mg, metformin, sitagliptin, and glipizide were associated with better-presenting VA, lower-presenting CST, lower prevalence of macular edema at final visit, and lower final CST, respectively, none of these systemic agents or glycemic control were associated with decreased treatment burden or improved visual outcomes in diabetics with CRVO.

Sitagliptin and Acute Pancreatitis: A Systematic Review and Meta-analysis

Background and Objectives: Sitagliptin is a dipepidyl peptidase inhibitor (DPP-4i) with gentle antidiabetic effects with a lower risk of hypoglycemia. The association with acute pancreatitis is controversial. The current meta-analysis aimed to assess the relationship of sitagliptin and acute pancreatitis.&#x0D; Methods: The literature in PubMed and Google Scholar was searched for relevant articles published in the last ten years up to September 2021. The keywords sitagliptins, DPP-4i, acute pancreatitis were used with the protean AND or OR. Among the 204 articles retrieved, 24 full-texts were assessed for eligibility and only five studies (Three from the USA, one from Asia, and one from Canada) met the inclusion criteria for the systematic review. The author name, year of publication, country, type of study, number of patients, and the duration of the study were reported.&#x0D; Results: There were five studies. The total number of patients were 729808 with 6459 events. The studies showed no increased rate of acute pancreatitis following sitagliptin use, odd ratio, 0.79, 95% CI, 0.29-2.15, a significant heterogeneity was observer, I2 for heterogeneity=98%, P-value, &lt;001, the P-value for overall effect was 0.65 and the chi-square, 160.15.&#x0D; Interpretation and Conclusion: Sitagliptin use is not associated with acute pancreatitis.

Therapeutic Role of Dipeptidyl Peptidase-4 Inhibitors in COVID-19

Background: Limited retrospective data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin may decrease mortality in patients with type 2 diabetes hospitalized with coronavirus disease 2019 (COVID-19). Objective: To review the strength of evidence that supports possible therapeutic role of DPP-4 inhibitors in COVID-19. Methods: PUBMED search until October 10, 2020. Search terms included COVID-19, DPP-4 inhibitors, sitagliptin, CD26, mortality, diabetes. Retrospective studies, pertinent animal investigations and pre-print studies are reviewed. Results: Three retrospective studies have shown that use of DPP-4 inhibitors was associated with significant mortality reduction of approximately 56- 87% in patients with diabetes admitted with COVID-19. In addition, in one of these studies, the use of sitagliptin before hospitalization was associated with greater number of hospital discharges, improvement of clinical status, reduced risk of transfer to intensive care unit (ICU) and need for mechanical ventilation compared with patients who were not receiving sitagliptin. Moreover, there was significant decrease in some pro-inflammatory markers in the sitagliptin group. A small retrospective study of 9 patients who were taking a DPP-4 inhibitor prior to admission did not find any significant effect of DPP-4 inhibitors on mortality and clinical outcomes after hospitalization. Results of another small study suggested increase susceptibility to COVID-19, but not to its severity, in patients taking DPP-4 inhibitors. Conclusions: Weak evidence derived from observational studies suggests possible beneficial effects of DPP-4 inhibitors use in patients with type 2 diabetes and COVID-19. Randomized trials are urgently needed to clarify the efficacy and safety of DPP-4 inhibitors in patients with COVID-19 with and without type 2 diabetes

Combined use of GABA and sitagliptin promotes human β-cell proliferation and reduces apoptosis.

γ-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent β-cell survival and function. In human β-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic β-cell protective effect in mice islets. However, it remains unclear whether this combination has similar effects on human β-cell. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-gamma mice with streptozotocin-induced diabetes, and then treated them with GABA, Sita, or both. The oral administration of either GABA or Sita ameliorated blood glucose levels, increased transplanted human β-cell counts and plasma human insulin levels. Importantly, the combined administration of the drugs generated significantly superior results in all these responses, as compared to the monotherapy with either one of them. The proliferation and/or regeneration, improved by the combination, were demonstrated by increased Ki67+, PDX-1+, or Nkx6.1+ β-cell numbers. Protection against apoptosis was also significantly improved by the drug combination. The expression level of α-Klotho, a protein with protective and stimulatory effects on β cells, was also augmented. Our study indicates that combined use of GABA and Sita produced greater therapeutic benefits, which are likely due to an enhancement of β-cell proliferation and a decrease in apoptosis.

Do DPP-4 Inhibitors Protect against COVID-19?

Background: Limited retrospective data suggest that the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin may decrease mortality in patients with type 2 diabetes admitted with coronavirus disease 2019 (COVID-19). Objective: To review the strength of evidence that supports possible protective role of sitagliptin in COVID-19. Methods: PUBMED search until October 5, 2020. Search terms included COVID-19, sitagliptin, DPP-4, CD26, mortality, diabetes. Retrospective studies and pertinent animal and human studies are reviewed. Results: One retrospective study (n=338) showed that sitagliptin use before hospitalization was associated with significant mortality reduction of approximately 60% in patients with type 2 diabetes and COVID-19. Pre-admission sitagliptin administration was associated with greater number of hospital discharge, improvement of clinical status, reduced risk of transfer to intensive care unit (ICU) and need for mechanical ventilation compared with patients who were not receiving sitagliptin. In addition, there was significant decrease in some pro-inflammatory markers in the sitagliptin group. Another small retrospective study of 9 patients who were taking a DPP-4 inhibitor prior to admission did not find any significant effect of DPP-4 inhibitors on mortality and clinical outcomes after hospitalization. Conclusions: Weak evidence from observational studies suggests possible beneficial effects of sitagliptin use before hospital admission in patients with type 2 diabetes and COVID-19. Randomized trials are urgently needed to clarify the efficacy and safety of in-hospital sitagliptin administration in patients with COVID-19 with and without type 2 diabetes.

The effect of various classes of glucose-lowering medications on the blood vessel elasticity in patients with type 2 diabetes

Aim. To study the effect of various classes of glucose-lowering agents (dipeptidyl peptidase-4 (DPP-4) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors) on the vascular stiffness in patients with type 2 diabetes (T2D) and high cardiovascular risk.Material and methods. The open-label, prospective 24-week study included 120 patients with T2D and high cardiovascular risk. We evaluated the effect of modern glucose-lowering medications, empagliflozin at a dose of 25 mg/day (SGLT-2 inhibitor) and sitagliptin at a dose of 100 mg/day (DPP-4 inhibitor), on vascular elasticity, central hemodynamic and laboratory parameters.Results. After 24-week therapy, the target glycated hemoglobin level reached 71% and 80% of patients in the sitagliptin and empagliflozin groups, respectively. In both groups, vascular stiffness and central hemodynamic parameters were improved. However, significant changes were recorded only in the empagliflozin (carotid-femoral pulse wave velocity decreased by 14,4%, augmentation index — by 6%, central pulse pressure — by 7,8%) (p&lt;0,05). Use of sitagliptin was associated with significant improvements in the lipid profile (total cholesterol decreased by 9,5%, triglycerides — by 21%, low density lipoproteins — by 15,1%; high density lipoproteins increased by 15,7%) (p&lt;0,05). In the empagliflozin group, anthropometric parameters were improved (body mass index decreased by 9,1%, waist circumference — by 4,1%) (p&lt;0,05). Patients in both groups had a significant decrease in HOMA-IR index and highly sensitive C-reactive protein: by 34% and 51,6% in the empagliflozin group and by 31,8% and 22,1% in the sitagliptin group, respectively (p&lt;0,05).Conclusion. The use of empagliflozin is more associated with arterial stiffness decrease in T2D patients with high cardiovascular risk compared with sitagliptin.

A randomized, open-label, active comparator trial assessing the effects of 26 weeks of liraglutide or sitagliptin on cardiovascular function in young obese adults with type 2 diabetes.

To compare the effects of a glucagon-like peptide-1 receptor agonist and a dipeptidyl peptidase-4 inhibitor on magnetic resonance imaging-derived measures of cardiovascular function. In a prospective, randomized, open-label, blinded endpoint trial liraglutide (1.8 mg) and sitagliptin (100 mg) were compared in asymptomatic, non-insulin treated young (aged 18-50 years) adults with obesity and type 2 diabetes. The primary outcome was difference in circumferential peak early diastolic strain rate change (PEDSR), a biomarker of cardiac diastolic dysfunction 26 weeks after randomization. Secondary outcomes included other indices of cardiac structure and function, HbA1c and body weight. Seventy-six participants were randomized (54% female, mean ± SD age 44 ± 6 years, diabetes duration 4.4 years, body mass index 35.3 ± 6.1 kg m-2 ), of whom 65% had ≥1 cardiovascular risk factor. Sixty-one participants had primary outcome data available. There were no statistically significant between-group differences (intention-to-treat; mean [95% confidence interval]) in PEDSR change (-0.01 [-0.07, +0.06] s-1 ), left ventricular ejection fraction (-1.98 [-4.90, +0.94]%), left ventricular mass (+1.14 [-5.23, +7.50] g) or aortic distensibility (-0.35 [-0.98, +0.28] mmHg-1 × 10-3 ) after 26 weeks. Reductions in HbA1c (-4.57 [-9.10, -0.37] mmol mol-1 ) and body weight (-3.88 [-5.74, -2.01] kg) were greater with liraglutide. There were no differences in cardiovascular structure or function after short-term use of liraglutide and sitagliptin in younger adults with obesity and type 2 diabetes. Longer studies in patients with more severe cardiac dysfunction may be necessary before definitive conclusions can be made about putative pleiotropic properties of incretin-based therapies.

The Relationship Between Dipeptidyl Peptidase-4 Inhibitor Usage and Asymptomatic Amylase Lipase Increment in Type 2 Diabetes Mellitus Patients.

In different studies, it has been shown that the use of dipeptidyl peptidase-4 (DPP-4) inhibitors (DPP-4 inh) does not increase the risk of pancreatitis or pancreatic cancer. Although the number of studies involving clinical pancreatitis clinics is sufficient, the number of studies involving clinical non-pancreatitis hyperamylasemia is rare. The aim of the study was to investigate the relationship between DPP-4 inh usage and amylase and lipase increment without clinical pancreatitis symptoms. Eighty-seven patients who met the inclusion criteria were enrolled. The patients were divided into 3 groups according to their use of saxagliptin, sitagliptin, or vildagliptin. All patients included in the study were receiving metformin at a dose of 2 g/day. Fasting blood glucose, postprandial blood glucose, HbA1C, serum creatinine, ALT, amylase, and lipase results were recorded at the beginning of treatment and at the end of 3 months. There was an increase in all groups in terms of amylase and lipase values but there was no significant difference between the groups in terms of increase (p>0.05) There was no statistically significant increase in the saxagliptin and vildagliptin groups (p>0.05) when the baseline and 3-month values of lipase and amylase increase were examined. However, there was a statistically significant increase in amylase and lipase in the sitagliptin group (p<0.05). The use of DPP-4 inh can increase amylase and lipase levels without clinical findings of acute pancreatitis in the patient. DPP-4 inh should be used with caution in patients at risk for pancreatitis and pancreatic cancer. Patients using DPP-4 inh, especially sitagliptin, should be evaluated carefully for pancreatitis risk factors.