Treatment Of Type 2 Diabetes Mellitus Patients Research Articles

Longitudinal assessment of coronary plaque regression related to sodium–glucose cotransporter-2 inhibitor using coronary computed tomography angiography

BackgroundSodium–Glucose Cotransporter-2 Inhibitor (SGLT2i) is a novel oral drug for treating type 2 diabetes mellitus (T2DM) with demonstrated cardiovascular benefits. Previous studies in apolipoprotein E knockout mice have shown that SGLT2i is associated with attenuated progression of atherosclerosis. However, whether this effect extends to T2DM patients with coronary atherosclerosis in real-world settings remains unknown.MethodsIn this longitudinal cohort study using coronary computed tomography angiography (CCTA), T2DM patients who underwent ≥ 2 CCTA examinations at our center between 2019 and 2022 were screened. Eligible patients had multiple study plaques, defined as non-obstructive stenosis at baseline and not intervened during serial CCTAs. Exclusion criteria included a CCTA time interval < 12 months, prior SGLT2i treatment, or initiation/discontinuation of SGLT2i during serial CCTAs. Plaque volume (PV) and percent atheroma volume (PAV) were measured for each study plaque using CCTA plaque analysis software. Patients and plaques were categorized based on SGLT2i therapy and compared using a 1:1 propensity score matching (PSM) analysis.ResultsThe study included 236 patients (mean age 60.5 ± 9.5 years; 69.1% male) with 435 study plaques (diameter stenosis ≥ 50%, 31.7%). Following SGLT2i treatment for a median duration of 14.6 (interquartile range: 13.0, 20.0) months, overall, non-calcified, and low-attenuation PV and PAV were significantly decreased, while calcified PV and PAV were increased (all p < 0.001). Meanwhile, reductions in overall PV, non-calcified PV, overall PAV, and non-calcified PAV were significantly greater in SGLT2i-treated compared to non-SGLT2i-treated plaques (all p < 0.001). PSM analysis showed that SGLT2i treatment was associated with higher reductions in overall PV (− 11.77 mm3 vs. 4.33 mm3, p = 0.005), non-calcified PV (− 16.96 mm3 vs. − 1.81 mm3, p = 0.017), overall PAV (− 2.83% vs. 3.36%, p < 0.001), and non-calcified PAV (− 4.60% vs. 0.70%, p = 0.003). These findings remained consistent when assessing annual changes in overall and compositional PV and PAV. Multivariate regression models demonstrated that SGLT2i therapy was associated with attenuated progression of overall or non-calcified PV or PAV, even after adjusting for cardiovascular risk factors, medications, and baseline overall or non-calcified PV or PAV, respectively (all p < 0.05). The effect of SGLT2i on attenuating non-calcified plaque progression was consistent across subgroups (all p for interaction > 0.05).ConclusionsIn this longitudinal CCTA cohort of T2DM patients, SGLT2i therapy markedly regressed coronary overall PV and PAV, mainly result from a significant reduction in non-calcified plaque.Graphical abstract

Analysis Of Direct Medical Cost Of Insulin Treatment In Outpatient With Type 2 Diabetes Mellitus On Payer Perspective

Type 2 diabetes mellitus (T2DM) is a global health issue that affect around 643 million people in 2030. Estimated prevalence of T2DM in adults aged 20–79 years has more than tripled, from an estimated 151 million (4.6% of the global population at the time) to 537 million (10.5%) today. This study analyze direct medical costs of insulin treatment with in T2DM outpatients. This retrospective descriptive economic evaluation was conducted in April 2023 on the basis of payer (called as Badan Penyelenggara Jaminan Sosial abbreviated as BPJS) perspective, then only direct costs were included in this study. Component of direct medical cost of this research include drug acquisition costs, physician service, laboratory examination, medical execution and administration. 58 T2DM outpatients met inclusion criteria in Universitas Sumatera Utara was recruited by simple random sampling. Result of this study show that most of respondent were aged 56-65 years (58.89%). Cost/year/patient of drug acquisition costs was Rp.4,7228,970.14; physician service was Rp.1,865,172.41; laboratory examination was Rp.443,379.31; and medical execution was Rp.31,030.48 and administration was Rp.300,000.00, respectively. Drug acquisition costs was the largest cost in treating T2DM patients with insulin treatment.

Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergometformin monotherapy.This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Abstract P431: Heparin-Warfarin Administered for Pulmonary Vein Thrombi Partially Dissolves Thrombi and Ameliorates Mild to Moderate Type 2 Diabetes Mellitus

Background: Pulmonary infection generates arterial thrombi, an important component of which are neutrophil extracellular traps, to defend the host. Pulmonary vein thrombi (PVTs) are underrated compared to arterial thrombi. In 2014, we reported that at least 61% (35 of 57) of elderly patients with chest pain had PVTs, as estimated using cardiac computed tomography (CT), and in 2022, we reported that 98.6% (215 of 218) of senior patients with age-related diseases such as hypertension, dyslipidemia, and type 2 diabetes mellitus (T2DM) had PVTs, as evaluated using cardiac CT and transesophageal echocardiography. T2DM is a common disease that can cause atherosclerosis, leading to ischemic stroke and acute myocardial infarction. It is important to better understand the mechanisms of T2DM and how to treat T2DM patients. The relationships between PVTs and T2DM are still unclear. Additionally, the relationships between heparin-warfarin therapy and T2DM are unknown. Methods: We identified PVTs in 15 T2DM patients (73.5 ± 9.9 y.o., range 50 y.o. to 88 y.o.; 10 males and 5 females) using both cardiac CT and transesophageal echocardiography. Among the 15 patients, two did not take DM medications; one took one DM medication; one took two DM medications; five took three DM medications; four took 4 DM medications; one took 5 DM medications; and one was treated with insulin. Results: The PVTs were partially dissolved by standard doses of heparin and warfarin given at the same time for one month. During the treatment, blood glucose levels were examined 30 minutes before breakfast, lunch, dinner and sleep. Between one and two weeks, the blood glucose levels of 10 patients decreased, especially before lunch, and some patients showed symptoms of hypoglycemia; therefore, the number of administered DM medications was decreased to zero for 6 patients and to one for 4 patients. After one month, the patients’ HbA1c levels had decreased slightly. We treated 10 patients with warfarin for the next several months, none of whom needed to resume DM medications, although their blood glucose tended to increase slightly. Three patients with comparatively severe T2DM showed no change in blood glucose following therapy. Conclusions: Heparin-warfarin therapy partially dissolved PVTs and decreased DM medications in patients with mild to moderate T2DM.

Effect of Empagliflozin Treatment on Ventricular Repolarization Parameters.

An example of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor is Empagliflozin. It is a new medicine for treating type 2 diabetes mellitus (T2DM), but there is increasing interest in how empagliflozin affects the heart. This study aims to examine the impact of empagliflozin treatment on ventricular repolarization parameters in T2DM patients. T2DM patients were included in a prospective study. Measurements of ventricular repolarization parameters, including QT interval, corrected QT interval (QTc), QT dispersion (QTd), Tpeak-to-Tend interval (Tp-e), and Tpeak-to-Tend interval corrected for QTc (Tp-e/QTc), were obtained before initiating empagliflozin treatment and six months following treatment initiation. Statistical analysis was performed to assess changes in these parameters. In this study, 95 patients were diagnosed with T2DM out of 177 patients. Among T2DM patients, 40 were male (42%) compared to 48% males in controls (p = 0.152). The average age of the T2DM patients was 60.2 9.0 years, compared to 58.2 9.2 years in the control group (p = 0.374). When comparing pre- and post-treatment measurements of parameters representing ventricular repolarization (QT 408.5 22.9/378.8 14.1, p 0.001; QTc 427.0 20.5/404.7 13.8, p 0.001; QTd 52.1 1.2/47.8 1.7, p 0.001; Tp-e 82.3 8.7/67.1 5.1, p 0.001; Tp-e/QTc 0.19 0.01/0.17 0.01, p 0.001 (respectively)), statistically significant improvements were observed. A statistically significant dose-dependent decline in the magnitude of change in the QTc parameter (19.4/29.6, p = 0.038) was also observed. According to these results, empagliflozin may decrease the risk of potential ventricular arrhythmias.

Clinical efficacy of Huanglian Wendan decoction in treating type 2 diabetes mellitus: A systematic review and meta-analysis.

Huanglian Wendan decoction (HLWDD) is a traditional Chinese prescription, which has been used to treat type 2 diabetes mellitus (T2DM) in recent years. However, no studies have evaluated its underlying clinical efficacy. Therefore, we used systematic review and meta-analysis to explore the clinical efficacy of HLWDD in treating T2DM. The randomized controlled trials of HLWDD on T2DM were retrieved from Chinese and foreign databases. The primary outcomes included fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPG), and glycosylated hemoglobin, type A1c (HbA1c). The secondary outcomes included fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c). Statistical analyses were performed using Review Manager and Stata software. Mean difference (MD) with 95% confidence intervals (CI) were used to describe results. The grades of recommendation assessment, development and evaluation approach was used to rate the quality of the evidence; and trial sequential analysis was used to evaluate the required information size and treatment benefits. Twenty-three randomized controlled trials were included in this study. We showed that HLWDD can improve FBG (MD = -0.99, 95% CI: -1.10 to -0.88), 2hPG (MD = -1.57, 95% CI: -1.97 to -1.17), HbA1c (MD = -1.11, 95% CI: -1.42 to -0.80), HOMA-IR (MD = -0.80, 95% CI: -1.80 to -0.51), TC (MD = -0.65, 95% CI: -0.88 to -0.42), TG (MD = -0.32, 95% CI: -0.38 to -0.27), LDL-c (MD = -0.54, 95% CI: -0.66 to -0.41), and HDL-c (MD = 0.08, 95% CI: 0.02-0.15) levels in T2DM patients. Trial sequential analysis suggested that the eficacy of HLWDD in improving FBG, 2hPG, HbA1c, HOMA-IR, TC, TG, LDL-c, and HDL-c was sufficient to draw a firm conclusion. Grades of recommendation assessment showed that HLWDD only has high or moderate quality of evidence in improving FBG, and TG. HLWDD can improve blood glucose and blood lipid levels in T2DM patients, and may be a potential drug to treat T2DM.

Deficiencies in the Recognition and Reporting of Chronic Kidney Disease in Patients With Type 2 Diabetes Mellitus; A Hungarian Nationwide Analysis.

Objectives: Recognition of chronic kidney disease (CKD) is crucial in type 2 diabetes mellitus (T2DM). We conducted a nationwide epidemiological study to evaluate T2DM-associated CKD in Hungary between 2016 and 2020. Methods: Annual incidence and prevalence rates of registered CKD amongst all pharmacologically treated T2DM patients were analyzed in different age-groups by the central database of the Hungarian Health Insurance Fund Management. Statistical methods included Poisson regression, Bonferroni test, Chi-square test. Results: We found 499,029 T2DM patients and 48,902 CKD patients in 2016, and 586,075 T2DM patients and 38,347 CKD patients in 2020. The majority of all prevalent T2DM and CKD patients were older (aged 60-69years: 34.1% and 25.8%; ≥70years: 36.1% and 64.4%, respectively). The annual incidence of T2DM and incidence rates of CKD in T2DM decreased in 2017-2020 (p < 0.001). The annual prevalence of T2DM increased (p < 0.01), the prevalence rates of CKD in T2DM were low and decreased from 9.8% to 6.5% in 2016-2020 (p < 0.001). Conclusion: Incidence and prevalence of T2DM-associated CKD decreased significantly in Hungary in 2016-2020. Lower prevalence rates of CKD may suggest under-recognition and/or under-reporting.

Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is among the commonest malignancies associated with significant cancer-related death. The identification of chemo-preventive agents following HCC treatments with the potential to lower the risk of HCC adverse course is intriguing. Metformin, a first-line agent used in the treatment of type 2 diabetes mellitus (T2DM), has been associated with inhibition of HCC growth. To determine whether metformin can prevent adverse events (i.e., death, tumor progression, and recurrence) after any HCC treatment in T2DM patients. A systematic review of the published literature was undertaken focused on the role of metformin on outcomes in patients with T2DM and HCC receiving any tumor therapy. A search of the PubMed and Cochrane Central Register of Con-trolled Trials Databases was conducted. A total of 13 studies (n = 14886 patients) were included in this review. With regard to the risk of death, a decreased risk was reported in cases receiving metformin, although this decrease was not statistically significant [odds ratio (OR) = 0.89, P = 0.42]. When only patients treated with curative strategies were considered, a more marked correlation between metformin and favorable cases was reported (OR = 0.70, P = 0.068). When analyzing palliative treatment, there was no statistical significance in terms of the correlation between metformin and favorable cases (OR = 0.74, P = 0.66). As for the risks of progressive disease and recurrence, no obvious correlation between metformin use and reduced risk was reported. When sub-analyses were performed for patients from different regions, the results for patients from Eastern countries showed a tendency for decreased risk of death in T2DM cases receiving metformin (OR = 0.69, P = 0.17), but the same was not seen in patients from Western countries (OR = 1.19, P = 0.31). Metformin failed to show a marked impact in preventing adverse effects after HCC treatment. A trend was reported in T2DM cases receiving curative therapies in relation to the risk of death, especially in patients from Eastern regions. Great heterogeneity was reported among the different studies. Further large studies are required to definitively clarify the real impact of metformin as a chemopreventive agent for HCC.

Monocytic HLA-DR expression in type 2 diabetes mellitus: Impact on disease susceptibility

Monocytes are innate immune cells that act as antigen-presenting cells. HLA-DR is a cell surface protein that plays a crucial role in the immune system by presenting antigens to CD4 T Cells (T helper). Based on surface expression, monocytes can differentiate into three subsets; classical monocytes (CD14+CD16-), intermediates monocytes (CD14+ CD16+), and non-classical monocytes (CD14dim CD16+). Among these subsets, classical monocytes have the lowest, and intermediate monocytes have the highest expression of HLA-DR. Monocytes are very sensitive to environmental changes, like hyperglycemia in Type 2 Diabetes Mellitus (T2DM). Metabolic changes in T2DM conditions trigger changes in immune cells including monocytes. Chronic low-grade inflammation in T2DM decreased HLA-DR expression in all monocyte subsets. Monocytes that do not express or lose HLA-DR expression are known as CD14+HLA-DR-/low monocyte and is immunosuppressive. This increase in monocytes in T2DM conditions is related to the ability of monocytes as antigen-presenting cells. Decreased HLA-DR expression increased the risk of severity and susceptibility to several diseases such as COVID-19 infection, TB, cancer, or sepsis. The alterations in HLA-DR expression are one of the factors that make T2DM a comorbid disease. This literature review aims to explore monocytic HLA-DR in T2DM conditions hence increasing the risk of severity and susceptibility to disease. This literature is expected to be the basis for research on the potential of HLA-DR as a prevention or treatment for T2DM patients.

Pioglitazone use increases risk of Alzheimer's disease in patients with type 2 diabetes receiving insulin

Pioglitazone is an insulin resistance inhibitor widely used as monotherapy or combined with metformin or insulin in treating type 2 diabetes mellitus (T2DM). This study further investigated the relationship between pioglitazone use and the risk of developing Alzheimer's disease (AD) in patients newly diagnosed with T2DM, and examined the potential impact of insulin use on this association. Data were extracted from the National Health Insurance Research Database (NHIRD) of Taiwan. Our data exhibited that the risk of developing AD in the pioglitazone group was 1.584-fold (aHR = 1.584, 95% CI 1.203–1.967, p < 0.05) higher than that in the non-pioglitazone controls. Compared to patients without both insulin and pioglitazone, higher cumulative risk of developing AD was found in patients receiving both insulin and pioglitazone (aHR = 2.004, 95% CI = 1.702–2.498), pioglitazone alone (aHR = 1.596, 95% CI = 1.398–1.803), and insulin alone (aHR = 1.365, 95% CI = 1.125–1.572), respectively (all p < 0.05). A similar observation also found in the evaluation the use of diabetic drugs with a cumulative defined daily dose (cDDD). No interaction between pioglitazone and major risk factors (comorbidities) of AD was observed. In conclusion, alternative drug therapies may be an effective strategy for reducing risk of developing AD in T2DM patients.

Effects of neprilysin and neprilysin inhibitors on glucose homeostasis: Controversial points and a promising arena

Neprilysin (NEP) is a transmembrane zinc-dependent metalloproteinase that inactivates various peptide hormones including glucagon-like peptide 1 (GLP-1). NEP inhibitors may be effective in the management of type 2 diabetes mellitus (T2DM) by increasing the circulating level of GLP-1. However, acute-effect NEP inhibitors may lead to detrimental effects by increasing blood glucose independent of GLP-1. These findings suggest a controversial point regarding the potential role of NEP inhibitors on glucose homeostasis in T2DM patients. Therefore, this perspective aimed to clarify the controversial points concerning the role of NEP inhibitors on glucose homeostasis in T2DM. NEP inhibitors may lead to beneficial effects by inhibition of NEP, which is involved in the impairment of glucose homeostasis through modulation of insulin resistance. NEP increases dipeptidyl peptidase-4 (DPP4) activity and contributes to increasing active GLP-1 proteolysis so NEP inhibitors may improve glycemic control through increasing endogenous GLP-1 activity and reduction of DPP4 activity. Thus, NEP inhibitors could be effective alone or in combination with antidiabetic agents in treating T2DM patients. However, long-term and short-term effects of NEP inhibitors may lead to a detrimental effect on insulin sensitivity and glucose homeostasis through different mechanisms including augmentation of substrates and pancreatic amyloid deposition. These findings are confirmed in animal but not in humans. In conclusion, NEP inhibitors produce beneficial rather than detrimental effects on glucose homeostasis and insulin sensitivity in humans though most of the detrimental effects of NEP inhibitors are confirmed in animal studies.

Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 16 RCTs.

Nonalcoholic fatty liver disease (NAFLD) is a common comorbidity of type 2 diabetes mellitus (T2DM). Our aim is to investigate the effects of liraglutide on T2DM with NAFLD. Relevant articles published from the earliest publication to March 2022 were selected from several databases. The Cochrane Collaboration's RevMan software was used for the analysis. Sixteen studies are selected for this meta-analysis, which includes totally 634 patients in the treatment group and 630 patients in the control group. As a result, 14 studies show that fasting plasma glucose levels of the experimental group are lower than that of the control group; 15 studies show that glycosylated hemoglobin A1c levels of the experimental group are lower than that of the control group; 13 studies show that triglyceride levels of the experimental group are lower than that of the control group; twelve studies show that total cholesterol levels of the experimental group are lower than that of the control group; 10 studies show that alanine aminotransferase levels of the experimental group is lower than that of the control group; 10 studies show that no significant difference in changes in aspartate transaminase between 2 groups; 13 studies show that low density lipoprotein cholesterol levels of the experimental group is lower than that of the control group; 9 studies show that no significant difference in changes in high density lipoprotein cholesterol between 2 groups; 7 studies mentioned adverse effects and the difference is significant. Liraglutide is potentially curative for T2DM with NAFLD.

Egg Microneedle for Transdermal Delivery of Active Liraglutide.

Liraglutide, a human glucagon-like peptide-1 (GLP-1) analog, is promising for safely treating type 2 diabetes mellitus (T2DM), compared to insulin, by significantly reducing the risk of glucose-dependent hypoglycemia. Concerns related to injection prevent T2DM patients from taking liraglutide regularly, even though once-a-day subcutaneous (SC) injections. Dissolving microneedles (DMNs) are promising substitutes for SC injection and for improving patient convenience. However, there are two fundamental limitations: the low drug delivery due to incomplete insertion and loss of drug activity during DMN fabrication. Here, it is shown that an egg microneedle (EMN) designed with three functional layered structures can maintain the maximum activity of the loaded compound during DMN fabrication and deliver it completely into the skin, with the base layer allowing the complete delivery of liraglutide, and the shell layer maintaining the drug activity by mimicking the role of albumin in eggs. In a diabetic mouse model, liraglutide administration via EMN exhibited similar effect when compared to that of injection. Therefore, EMN-mediated liraglutide administration is a good potential option for replacing liraglutide injections in T2DM treatment.

Association of single nucleotide polymorphism and phenotype in type 2 of diabetes mellitus using Support Vector Regression and Genetic Algorithm

Precision Medicine is used to improve proper health care and patients' quality of life, one of which is diabetes. Diabetes Mellitus (DM) is a multifactorial and heterogeneous group of disorders characterized by deficiency or failure to maintain normal glucose homeostasis. About 90% of all DM patients are Type 2 Diabetes Mellitus (T2DM). Biological characteristics and genetic information of T2DM disease were obtained by looking for associations in Single Nucleotide Polymorphism (SNP) which allows for determining the relationship between phenotypic and genotypic information and identifying genes associated with T2DM disease. This research focuses on the Support Vector Regression method and Genetic Algorithm to obtain SNPs that have previously calculated the correlation value using Spearman's rank correlation. Then do association mapping on the SNP results from the SVR-GA selection and check pastasis interaction. The results produced 14 SNP importance. Evaluation of the model using the mean absolute error (MAE) obtained is 0.02807. If the value of MAE is close to zero, then a model can be accepted. The genes generated from the association can be used to assist other researchers in finding the right treatment for T2DM patients according to their genetic profile.

Comorbidity clusters associated with newly treated type 2 diabetes mellitus: a Bayesian nonparametric analysis

Type 2 diabetes mellitus (T2DM) is associated with the development of chronic comorbidities, which can lead to high drug utilization and adverse events. We aimed to identify common comorbidity clusters and explore the progression over time in newly treated T2DM patients. The IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records, was used to identify all patients with a first-ever prescription for a non-insulin antidiabetic drug (NIAD) between January 2006 and December 2019. We selected 58 chronic comorbidities of interest and used Bayesian nonparametric models to identify disease clusters and model their progression over time. Among the 175,383 eligible T2DM patients, we identified the 20 most frequent comorbidity clusters, which were comprised of 14 latent features (LFs). Each LF was associated with a primary disease (e.g., 98% of patients in cluster 2, characterized by LF2, had congestive heart failure [CHF]). The presence of certain LFs increased the probability of having another LF active. For example, LF2 (CHF) frequently appeared with LFs related to chronic kidney disease (CKD). Over time, the clusters associated with cardiovascular diseases, such as CHF, progressed rapidly. Moreover, the onset of certain diseases led to further complications. Our models identified established T2DM complications and previously unknown connections, thus, highlighting the potential for Bayesian nonparametric models to characterize complex comorbidity patterns.

The Role of Physicians' Digital Tools in Pharmacological Management of Type 2 Diabetes Mellitus.

Background and Objectives: The constantly increasing prevalence of type 2 diabetes mellitus (T2DM) and the advent of new treatment options have made management of T2DM patients more demanding. We aimed to (a) estimate the familiarity of general practitioners with novel T2DM treatment options, (b) determine whether a digital tool can aid in their treatment decisions and (c) demonstrate that an evidence-based digital clinical support tool can be made using an existing digital platform. Materials and methods: This proof-of-concept study consisted of two parts: We first conducted a simple online survey among general practitioners of three European countries to estimate their familiarity with novel T2DM treatment options and to determine whether they believe that a digital tool can aid in their T2DM treatment decisions. We then proceeded to develop a new digital tool that provides quick, evidence-based support for treatment of patients with T2DM using an existing digital platform. Results: The online survey was completed by 129/5278 physicians (94 from Italy, 22 from Czech Republic and 13 from Slovenia). Only 30.7% of all general practitioners reported to be either very or extremely familiar with novel T2DM treatments; the vast majority of participating general practitioners (82.8%) reported that they would find a digital clinical decision support tool for treating T2DM patients either very or extremely useful. A digital tool which features the characteristics deemed most important by the polled physicians was subsequently developed. Conclusions: The results of the online survey showed that familiarity of general practitioners with novel T2DM treatment options is relatively low and that there is a need for digital clinical decision support tools intended to facilitate treatment decisions in T2DM patients. We demonstrated that such a tool can easily be developed using an existing digital platform.

Actions of Metformin in the Brain: A New Perspective of Metformin Treatments in Related Neurological Disorders.

Metformin is a first-line drug for treating type 2 diabetes mellitus (T2DM) and one of the most commonly prescribed drugs in the world. Besides its hypoglycemic effects, metformin also can improve cognitive or mood functions in some T2DM patients; moreover, it has been reported that metformin exerts beneficial effects on many neurological disorders, including major depressive disorder (MDD), Alzheimer’s disease (AD) and Fragile X syndrome (FXS); however, the mechanism underlying metformin in the brain is not fully understood. Neurotransmission between neurons is fundamental for brain functions, and its defects have been implicated in many neurological disorders. Recent studies suggest that metformin appears not only to regulate synaptic transmission or plasticity in pathological conditions but also to regulate the balance of excitation and inhibition (E/I balance) in neural networks. In this review, we focused on and reviewed the roles of metformin in brain functions and related neurological disorders, which would give us a deeper understanding of the actions of metformin in the brain.

Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Urine Albumin to Creatinine Ratio in Type 2 Diabetes Mellitus Patients and Medication Care.

Objectives The purpose of this study was to explore the effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on urine albumin to creatinine ratio (UACR) in type 2 diabetes mellitus (T2DM) patients and to recommend appropriate medication care scheme. Methods 8371 T2DM patients from four dapagliflozin studies and two canagliflozin studies were collected for analyzing with nonlinear mixed effect model (NONMEM). The change rates of UACR from baseline were intended to be evaluation indicators. Results In the present study, there was no significant difference in the effects on UACR using dapagliflozin or canagliflozin treatment in T2DM patients. The maximal effect (Emax) and the treatment duration of reaching half of Emax (ET50) from SGLT-2 inhibitors on UACR in T2DM patients were -19.2% and 0.448 weeks, respectively. Further, the treatment duration to reach 25%, 50%, 75%, and 80% Emax was 0.150 weeks, 0.448 weeks, 1.344 weeks, and 1.792 weeks, respectively. Namely, for achieving the plateau period (80% of Emax) of SGLT-2 inhibitors on UACR in T2DM patients, 10 mg/day dapagliflozin (or 100 mg/day canagliflozin) should be taken for at least 1.792 weeks. Conclusions To our knowledge, the present study explored the effects of SGLT-2 inhibitors on UACR in T2DM patients, meanwhile, recommended appropriate medication care scheme for the first time.

885-P: Real-World Evidence on Health Care Costs Related to Self-Monitoring of Blood Glucose (SMBG) Compared with Continuous Glucose Monitoring (CGM) in Nonintensively Treated Type 2 Diabetes Mellitus (T2DM)

Background: Type 2 diabetes poses an economic burden to healthcare systems. For individuals with non-intensively treated T2DM, it is unclear whether the use of CGM would add health-economic value. The aim of this study was to compare the costs of SMBG compared to CGM in non-intensively treated T2DM. Methods: A retrospective cost-analysis using the IBM® MarketScan® Databases was conducted. T2DM patients aged ≥18 years who were using SMBG or initiated CGM between Jan 2018 and March 20were eligible for inclusion. Inclusion criteria included two consecutive claims for T2DM or one claim for T2DM and a claim for glucose lowering therapy, at least one pharmacy claim for SMBG strips or CGM sensors and continuous enrollment for 1-year before and after the index date. Individuals with CGM in pre-index period, pregnancy, rapid-acting insulin, glucagon, T1DM, gestational or secondary diabetes were excluded. SMBG and CGM patients were matched using a propensity score and all cause costs during a one-year follow-up period were compared. Results: A total of 3,498 patients were included in each matched cohort. For CGM patients, 77% used flash monitoring and 23% a real-time CGM. 35% of SMBG and 37% of CGM users were on basal insulin. Considering median values, SMBG total healthcare costs per person/year were $1,934 less vs. CGM users (p &amp;lt; 0.05) . SMBG patients had significantly lower pharmacy cost (-$2,257, p&amp;lt;0.05) and lower expenses for glucose-lowering treatments (-$1,045, p&amp;lt;0.05) than CGM. Both SMBG and CGM cohorts had similar costs related to inpatient and emergency room admissions. Conclusion: This analysis shows that SMBG is less costly than CGM in non-intensively treated T2DM patients and is associated with lower pharmacy costs, including glucose-lowering medications. Furthermore, no significant differences in the number of emergency room visits or hospitalizations are seen in SMBG and CGM users. Disclosure D. Kerr: Advisory Panel; Abbott Diabetes, Novo Nordisk A/S, Sanofi. Consultant; Evidation Health. Research Support; Novo Nordisk A/S. Stock/Shareholder; Glooko, Inc., Hi.Health. I. Duncan: Consultant; Onduo LLC. F. Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. Consultant; Lilly Diabetes, Sanofi. Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. E. Repetto: Employee; Roche Diabetes Care. C. Perkins: Employee; Roche Diagnostics USA. R. Maroun: Employee; Amgen Inc., Roche Diagnostics. M. Rivers: Employee; Roche Diabetes Care. A. Wu: None.

Glucagon-like peptide-1 (GLP-1) receptor agonists and cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of double-blind, randomized, placebo-controlled clinical trials

BackgroundThe cardiovascular effects of glucagon-like peptide-1 (GLP-1) receptor agonists are still controversial in the treatment of type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the risk of cardiovascular events of GLP-1 (albiglutide, exenatide, liraglutide, semaglutide, lixisenatide and dulaglutide) receptor agonists in T2DM patients.MethodsPubMed and Embase were searched to find relevant randomized controlled trials (RCTs) from inception to June 2019 that evaluated the effect of GLP-1 receptor agonists on cardiovascular events in patients with T2DM. The T2DM patients of all the eligible trials received either GLP-1 therapy or placebo, and the cardiovascular outcomes included death from cardiovascular causes, fatal or non-fatal myocardial infarction and fatal or non-fatal stroke.ResultsWe included 6 multinational double-blind randomized placebo-control trials that included a total of 52821 T2DM patients. The results indicated that GLP-1 receptor agonists reduced the risk of death from cardiovascular causes (RR: 0.90; 95% CI: 0.83–0.97; P = 0.004) and fatal or non-fatal stroke (RR: 0.85; 95% CI: 0.77–0.94; P = 0.001) compared with the placebo controls. But GLP-1 receptor agonists did not significantly alter the fatal or non-fatal myocardial infarction compared with the placebo (RR: 0.91; 95% CI: 0.82 – 1.01; P = 0.06).ConclusionWe concluded that GLP-1 receptor agonist therapy could reduce the risk of death from cardiovascular causes and fatal or non-fatal stroke compared with the placebo in the treatment of T2DM patients in trials with cardiovascular outcomes.