Letter by Awadhesh Kumar Singh Regarding Article, “Cardiovascular Outcomes Comparison of Dipeptidyl Peptidase-4 Inhibitors Versus Sulfonylurea as Add-on Therapy for Type 2 Diabetes Mellitus: A Meta-Analysis”
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ABSTRACT:
SUBMITTER: Singh A
PROVIDER: S-EPMC8792819 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveRecent studies have raised concern about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review through meta-analysis to compare cardiovascular outcomes of sulfonylurea (SU) versus DPP4 inhibitors when used in combination with metformin.MethodsAfter searching for trials using combination therapy of metformin with DPP4 inhibitor or SU in PubMed, Cochrane Library, and Embase, one prospective observation study and 15 randomized controlled studies were selected.ResultsRegarding the primary analysis endpoint, there were no significant differences in the risk of all-cause mortality between SU and DPP4 inhibitors as an add-on therapy to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; p=0.811; I2=0%). Cardiovascular death was also similar between the two drug classes in the five studies which reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; p=0.517; I2=0%). Furthermore, there were no significant differences in major adverse cardiac events (MACE), coronary heart disease, myocardial infarction, ischemic stroke and heart failure. However, there were less hypoglycemic events and weight gain in the DPP4 inhibitor group as compared with the SU group (random-effect RR, 3.79; 95% CI, 1.53-9.39; p<0.001; I2=98.2 and weighted mean difference, 1.68; 95% CI, 1.07-2.29; p<0.001; I2=94.7, respectively).ConclusionAs add-on therapy to metformin, there were no significant differences in all-cause mortality and cardiovascular mortality between DPP4 inhibitors and SUs.
| S-EPMC8159755 | biostudies-literature
Project description:ObjectiveRecent studies have raised concerns about the cardiovascular safety of dipeptidyl peptidase-4 (DPP4) inhibitors. We performed a systematic review and meta-analysis to compare the cardiovascular outcomes of sulfonylureas (SUs) versus DPP4 inhibitors in combination with metformin.MethodsAfter searching for trials using combination therapy of metformin with an SU or DPP4 inhibitor in PubMed, Cochrane Library, and Embase, 1 prospective observational study and 15 randomized controlled studies were selected.ResultsRegarding the primary analysis endpoint, no significant differences were found in the risk of all-cause mortality between SUs and DPP4 inhibitors as add-on therapies to metformin (random-effect relative risk [RR], 1.14; 95% confidence interval [CI], 0.98-1.33; I2=0%; p=0.097). Cardiovascular death was also similar between SUs and DPP4 inhibitors in the 5 studies that reported outcomes (random-effect RR, 1.03; 95% CI, 0.83-1.27; I2=0%; p=0.817). Furthermore, there were no significant differences in major adverse cardiac events, coronary heart disease, myocardial infarction, and heart failure. However, the SU group showed a higher risk of ischemic stroke, more hypoglycemic events, and more weight gain than the DPP4 inhibitor group (ischemic stroke, random-effect RR, 2.78; 95% CI, 1.06-7.30; I2=51.9%; p=0.039; hypoglycemia, random-effect RR, 3.79; 95% CI, 1.53-9.39; I2=98.2; p=0.004; weight gain, weighted mean difference, 1.68; 95% CI, 1.07-2.29; I2=94.7; p<0.001).ConclusionAs add-on therapies to metformin, SUs and DPP4 inhibitors showed no significant differences in all-cause mortality and cardiovascular mortality. However, some of the favorable results of DPP4 inhibitors suggest good safety and feasibility of the drugs.
| S-EPMC8792822 | biostudies-literature
Project description:BackgroundSeveral clinical trials have addressed the therapeutic strategy of adding dipeptidyl peptidase 4 (DPP-4) inhibitors to the treatment of type 2 diabetes mellitus (DM) inadequately controlled by insulin therapy. However, there is a high degree of heterogeneity in these studies, and the cause of which has not been identified.MethodsWe conducted a meta-analysis of randomized controlled trials, which compared the efficacy and safety of adding DPP-4 inhibitors or placebo to insulin therapy; the level of hemoglobin A1c (HbA1c) in the patients was >7.0%, and the duration of treatment was ≥8 weeks. We focused on the mean changes in HbA1c from the baseline (ΔHbA1c) and the incidence of hypoglycemia. We assumed that five baseline parameters (HbA1c, fasting blood glucose, body mass index (BMI), duration of type 2 DM, and duration of treatment) could affect ΔHbA1c. Regarding the incidence of hypoglycemia, we suspected that the heterogeneity was caused by differences in the definition of hypoglycemia among the studies.ResultsData obtained from 11 studies (n = 4654 patients) were included in the analysis. The mean ΔHbA1c between the DPP-4 inhibitor and placebo groups was -0.61% (95% confidence interval (CI): -0.74 to -0.48, I 2 = 73.4%). There was substantial heterogeneity among the 11 studies, but 74.1% of this variability was explained by the difference in BMI. The odds ratio for the incidence of hypoglycemia was 1.02 (95% CI: 0.74 to 1.42, I 2 = 63.8%), with substantial heterogeneity due to differences in the definition of hypoglycemia among the studies. There was no apparent effect of publication bias.ConclusionsThe addition of DPP-4 inhibitors to insulin therapy for adult patients with type 2 DM can significantly reduce HbA1c levels without increasing the occurrence of hypoglycemia. BMI and hypoglycemia definition could explain the heterogeneity in the clinical trials. This trial is registered with PROSPERO #CRD42016035994.
| S-EPMC7673952 | biostudies-literature
Project description:This study aimed to investigate the association of add-on dipeptidyl peptidase-4 inhibitor (DPP4i) therapy and the progression of diabetic retinopathy (DR). In this retrospective population-based cohort study, we examined Taiwanese patients with type 2 diabetes, preexisting DR, and aged ≥40 years from 2009 to 2013. Prescription of DPP4i was defined as a medication possession ratio of ≥80% during the first 6 months. The outcomes included vitreous hemorrhage (VH), tractional retinal detachment, macular edema, and interventions including retinal laser therapy, intravitreal injection (IVI), and vitrectomy. Of 1,767,640 patients, 62,824 were eligible for analysis. After matching, the DPP4i and non-DPP4i groups each contained 20,444 patients. The risks of VH (p = 0.013) and macular edema (p = 0.035) were higher in the DPP4i group. The DPP4i group also had higher risks of receiving surgical interventions (retinal laser therapy (p < 0.001), IVI (p = 0.049), vitrectomy (p < 0.001), and any surgical intervention (p < 0.001)). More patients in the DPP4i group received retinal laser therapy (p < 0.001) and IVI (p = 0.001) than in the non-DPP4i group. No between-group differences in cardiovascular outcomes were noted. In the real-world database study, add-on DPP4i therapy may be associated with the progression of DR in patients with type 2 diabetes. No additional cardiovascular risks were found. The early progression of DR in rapid glycemic control was inconclusive in our study. The possible effect of add-on DPP4i therapy in the progression of DR in patients with type 2 diabetes requires further research.
| S-EPMC8269314 | biostudies-literature
Project description:BackgroundExcess adiposity is associated with an increased risk of cardiovascular disease due to metabolic changes in the body. Visceral obesity increases the risk of diabetes mellitus through adipocytokines and hence the effective targeting therapies are essential to control obesity in high-risk individuals. The study's main objective was to evaluate the effect of add-on therapy of sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors on visceral fat-associated serum adipokines.MethodsThe study included 90 subjects diagnosed with type 2 diabetes mellitus. The blood samples were taken before starting first-line therapy with metformin, 12 weeks after starting metformin therapy and 12 weeks after starting add-on therapy. Serum adipokines were analyzed with enzyme-linked immunosorbent assay (ELISA). Hemoglobin A1c (HbA1c) level was estimated with high-performance liquid chromatography (HPLC). The biochemical variables were measured using Cobas® 6000 analyzer.ResultsThe mean adiponectin level was significantly elevated with add-on therapy using SGLT2 inhibitors and DPP4 inhibitors (P < 0.001). The mean retinol binding protein 4 (RBP4), fatty acid binding protein 4 (FABP4) and visfatin levels were reduced considerably (P < 0.001). The SGLT2 inhibitors are more effective on serum FABP4 in patients with type 2 diabetes (P = 0.038). The mean fasting plasma glucose (FPG), postprandial blood glucose (PPBG) and HbA1c levels were reduced significantly with add-on therapy (P < 0.001). Lipid profile was also altered significantly with this add-on therapy (P < 0.001).ConclusionsThe results indicate that add-on therapy exerts a beneficial effect in type 2 diabetic patients insufficiently controlled with metformin only by altering the visceral fat-associated adipokine levels and controlling the metabolic activities.
| S-EPMC8256907 | biostudies-literature
Project description: Not available
| S-EPMC4492319 | biostudies-literature
Project description:BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitor has been reported to have kidney-protective benefits. To elucidate how antidiabetic agents prevent diabetic kidney disease progression, it is important to investigate their effect on the kidney environment in type 2 diabetes mellitus (DM) patients. Herein, we investigated the expression pattern of urinary exosome-derived microRNA (miRNA) in patients taking a combination of DPP-4 inhibitor and metformin (DPP-4 inhibitor group) and compared them with patients taking a combination of sulfonylurea and metformin (sulfonylurea group).MethodsThis was a prospective study involving 57 patients with type 2 DM (DPP-4 inhibitor group, n = 34; sulfonylurea group, n = 23) and healthy volunteers (n = 7). We measured urinary exosomal miRNA using the NanoString nCounter miRNA array (NanoString Technologies) across the three groups (n = 4 per each group) and validated findings using real-time polymerase chain reaction.ResultsTwenty-one differentially expressed candidate miRNAs were identified, and six (let-7c-5p, miR-23a-3p, miR-26a-3p, miR-30d, miR-205, and miR-200a) were selected for validation. Validation showed no significant difference in miRNA expression between the DPP-4 inhibitor and sulfonylurea groups. Only miR-23a-3p was significantly overexpressed in the diabetes group compared with the control group (DPP-4 inhibitor vs. control, p = 0.01; sulfonylurea vs. control, p = 0.007). This trend was consistent even after adjusting for age, sex, and body mass index.ConclusionThere was no significant difference in urine exosome miRNA expression between diabetic participants taking DPP-4 inhibitor and those taking sulfonylurea. The miR-23a levels were higher in diabetic participants than in nondiabetic controls.
| S-EPMC8476296 | biostudies-literature
Project description:Effect of expression of dipeptidyl peptidase-IV (DPP-IV) in U373 cell line on uncontrolled cell proliferation and aberrant interactions with the brain extracellular matrix.
2011-12-31 | E-MTAB-583 | biostudies-arrayexpress
Project description:BackgroundPatients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM.MethodsPubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests.ResultsSix clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores.ConclusionsDPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients.Trial registration in prosperoCRD42023430873.
| S-EPMC10712048 | biostudies-literature
Project description:Type 2 diabetes mellitus (T2DM) has become one of the most prevalent noncommunicable diseases in the past years. It is undoubtedly associated with atherosclerosis and increased risk for cardiovascular diseases. Incretins, which are intestinal peptides secreted during digestion, are able to increase insulin secretion and its impaired function and/or secretion is involved in the pathophysiology of T2DM. Dipeptidyl peptidase 4 (DPP4) is an ubiquitous enzyme that regulates incretins and consequently is related to the pathophysiology of T2DM. DPP4 is mainly secreted by endothelial cells and acts as a regulatory protease for cytokines, chemokines, and neuropeptides involved in inflammation, immunity, and vascular function. In T2DM, the activity of DPP4 seems to be increased and there are a growing number of in vitro and in vivo studies suggesting that this enzyme could be a new link between T2DM and atherosclerosis. Gliptins are a new class of pharmaceutical agents that acts by inhibiting DPP4. Thus, it is expected that gliptin represents a new pharmacological approach not only for reducing glycemic levels in T2DM, but also for the prevention and treatment of atherosclerotic cardiovascular disease in diabetic subjects. We aimed to review the evidences that reinforce the associations between DPP4, atherosclerosis, and T2DM.
| S-EPMC4471315 | biostudies-other