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:Dipeptidyl peptidase 4 (DPP-4) is a novel adipokine and may be involved in the association between adipose tissue and metabolic syndrome. We investigated DPP-4 and adiponectin levels in the serum, subcutaneous adipose tissue (SAT), and epicardial adipose tissue (EAT), and their relationship with preoperative factors, as well as comparing the DPP-4 levels in SAT and EAT with and without DPP-4 inhibitors. This study included 40 patients (25 men, age 67.5 ± 13.8 years). The serum adipokine, DPP-4, and adiponectin levels in SAT and EAT were measured using ELISA and Western blotting. The DPP-4 and adiponectin levels were significantly higher in the SAT than in the EAT. The serum DPP-4 and DPP-4 activity levels had no correlation with the DPP-4 levels in the SAT and EAT, but the DPP-4 levels in the SAT and EAT had a positive correlation. The DPP-4 levels in the SAT were positively correlated with atherosclerosis, diabetes mellitus, DPP-4-inhibitor use, and fasting blood glucose. The DPP-4 levels in the EAT showed a negative correlation with eGFR and a positive correlation with atrial fibrillation. The DPP-4 activity in the serum had a lower tendency in the group taking DPP-4 inhibitors than in the group not taking them. DPP-4 inhibitors may suppress angiogenesis and adipose-tissue hypertrophy.
| S-EPMC9331841 | biostudies-literature
Project description:BackgroundTo determine the impact of dipeptidyl peptidase-4 inhibitor (DPP4i) on the risk of major cardiocerebrovascular and renal outcomes compared with sulfonylurea (SU) combined with metformin in patients with type 2 diabetes from a population-based cohort.MethodsFrom a nationwide cohort in Korea (2008-2013), 23,674 patients with type 2 diabetes treated with DPP4i plus metformin or SU plus metformin were selected and matched by propensity score. Composite cardiocerebrovascular events including incident ischemic heart disease (IHD), ischemic stroke (IS), hospitalization for heart failure (HHF), and cardiocerebrovascular death, as well as renal events including incident end-stage renal disease or initiation of renal-replacement therapy were assessed by Cox proportional-hazards models.ResultsDuring a median follow-up of 19.6 months (interquartile range 7.2-36.4), 762 composite cardiocerebrovascular events and 17 end-stage renal events occurred. There was no significant difference in the risk of IHD (hazard ratio [HR], 1.00; 95% CI 0.81-1.23), IS (HR, 0.95; 95% CI 0.74-1.23), or cardiocerebrovascular death (HR, 0.74; 95% CI 0.46-1.18) in the DPP4i group compared to that in the SU group. Likewise, DPP4i therapy was not associated with the risk of end-stage renal outcomes (HR, 1.23; 95% CI 0.41-3.62). However, the risk of HHF was significantly higher in the DPP4i group than in the SU group (HR, 1.47; 95% CI 1.07-2.04).ConclusionsThis real-world database analysis showed that DPP4i therapy did not increase the overall risk of major cardiovascular and renal outcomes compared to SU therapy. However, the DPP4i-associated risk of HHF remained significant.
| S-EPMC6410523 | biostudies-literature
Project description:To review the current literature investigating the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk factors of cardiovascular disease (CVD).We conducted a search of PubMed and MEDLINE database, using the term DPP-4 inhibitor in combination with the following terms: metabolic syndrome, hypertension, dyslipidemia, insulin resistance, obesity, and CVD. We reviewed 100 relevant studies out of 227 articles, excluding single case reports, studies using animal models, and reports not written in English. We included 38 references in this review article.The majority of the recent clinical studies have demonstrated that DPP-4 inhibitors have beneficial effects on cardiovascular (CV) system. These agents may have the potential to lower blood pressure, improve lipid profile and endothelial dysfunction, decrease the macrophage-mediated inflammatory response, and prevent myocardial injury.DPP-4 inhibitors have some CV protective effects in type 2 diabetes mellitus (T2DM) in addition to their antidiabetic actions. Long-term outcome clinical trials are under way to investigate the effects of the DPP-4 inhibitors on the elevated CV risks in patients with T2DM. Further investigation in a large cohort is warranted to assess the exact mechanisms of CV protective effects of DPP-4 inhibitors.
| S-EPMC3654348 | biostudies-other
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: Not available
| S-EPMC4492319 | 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-EPMC8427028 | biostudies-literature