Oral Antidiabetic Medications Research Articles

SGLT2 inhibition, circulating proteins, and insomnia: A mendelian randomization study

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT2i) initially emerged as oral antidiabetic medication but were subsequently discovered to exhibit pleiotropic actions. Insomnia is a prevalent and debilitating sleep disorder. To date, the causality between SGLT2 inhibitors and insomnia remains unclear. This study aims to evaluate the causality between SGLT2 inhibitors and insomnia and identify potential plasma protein mediators. MethodsUsing a two-sample Mendelian Randomization (MR) analysis, we estimated the causality of SGLT2 inhibition on insomnia and sleep duration. Additionally, employing a two-step and proteome-wide MR analysis, we evaluated the causal link of SGLT2 inhibition on 4907 circulating proteins and the causality of SGLT2 inhibition-driven plasma proteins on insomnia. We applied a false discovery rate (FDR) correction for multiple comparisons. Furthermore, mediation analyses were used to identify plasma proteins that mediate the effects of SGLT2 inhibition on insomnia. ResultsSGLT2 inhibition was negatively correlated with insomnia (odds ratio [OR] = 0.791, 95 % confidence interval [CI] [0.715, 0.876], P = 5.579*10^-6) and positively correlated with sleep duration (β = 0.186, 95 % CI [0.059, 0.314], P = 0.004). Among the 4907 circulating proteins, diadenosine tetraphosphatase (Ap4A) was identified as being linked to both SGLT2 inhibition and insomnia. Mediation analysis indicated that the effect of SGLT2 inhibition on insomnia partially operates through Ap4A (β = −0.018, 95 % CI [−0.036, −0.005], P = 0.023), with a mediation proportion of 7.7 %. ConclusionThe study indicated a causality between SGLT2 inhibition and insomnia, with plasma Ap4A potentially serving as a mediator.

Berberine in the treatment of type 2 diabetes - literature review

Introduction and purpose : Type 2 diabetes is currently a serious problem worldwide. Each year, the number of individuals with carbohydrate metabolism disorders is increasing. This is due to an unhealthy lifestyle, lack of physical activity, and a diet rich in highly processed foods. Currently, the treatment of type 2 diabetes is based on the use of oral antidiabetic medications, with the first choice often being a derivative of biguanides, such as metformin. Berberine has been used in China for many years as a hypoglycemic agent, and its efficacy is compared to metformin preparations. This paper focuses on the benefits of using berberine in patients with prediabetes or type 2 diabetes and compares the effects of berberine preparations to classical medications used in diabetes treatment. Material and methods : The literaue was reviewed in PubMed and Google Scholar scientific database in 2013-2023 using the following keywords : berberine, diabetes mellitus type 2, hyperlipidemia, hyperglicemia Conclusions : The studies included in this manuscript have shown that berberine is a promising agent for adjunctive treatment in type 2 diabetes. It exhibits a range of positive effects such as lowering blood glucose levels, improving lipid profile, with no serious adverse effects reported. However, further research is needed to confirm these findings and develop an effective treatment plan.

Medication use before and after bariatric surgery: 5-year results from a randomised controlled trial of banded Roux-en-Y gastric bypass versus sleeve gastrectomy in patients with obesity and type 2 diabetes.

Bariatric surgery is an effective tool for weight loss and for improving weight related co-morbidities. Changes in medication usage after a silastic ring laparoscopic Roux-en-Y gastric bypass (SR-LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) are unknown. This was a single-centre, double-blind, randomised controlled trial. Patients were randomised to either SR-LRYGB or LSG. A medication history was obtained at regular follow-up intervals, and mean numbers of prescribed medications were analysed over 5 years. Poisson regression and generalised estimating equations were used to test for statistically significant changes in usage. After eight patients were lost to follow-up, data from 52 patients in each group were available for analysis. There was no difference between the SR-LRYGB or LSG groups in the number of medications prescribed, with the exception of oral glucose-lowering medications, where there was a greater decrease after SR-LRYGB compared to LSG (79% vs 55% respectively) from baseline to 5 years. At 5 years, total medication prescribed was down 10% from pre-operative levels. Prescribed insulin decreased by 72%, and cardiovascular medication decreased by 56% compared to baseline. Prescriptions for analgesia increased by 50%, psychiatric medications by 133% and proton-pump inhibitors by 81%. Both SR-LRYGB and LSG reduced requirement for diabetic and cardiovascular medications, but increased requirement for nutritional supplementation, analgesia and psychiatric medications. There was a greater reduction in oral anti-diabetic medication prescriptions following SR-LRYGB compared to LSG, but no other difference in medication usage between surgical groups was found.

Effect of SGLT2 Inhibitors on Post-PCI Outcomes after Acute Myocardial Infarction in Diabetic Patients: A Systematic Review and Meta-Analysis

Background: Acute myocardial infarction (AMI) is related with poor outcomes in patients with diabetes mellitus (DM). Whether diabetic patients with AMI undergoing percutaneous coronary intervention (PCI) benefit from sodium–glucose cotransporter 2 inhibitors (SGLT2i) in terms of cardiovascular mortality, myocardial damage, and left ventricular function is unclear. Methods: Through a comprehensive search in PubMed, EMBASE, and Web of science databases from January 2018 to September 2023, randomized controlled trials were performed to compare SGLT2i with other oral antidiabetic medications in diabetic patients with AMI undergoing PCI. Cardiovascular mortality constituted the primary outcome. Secondary outcomes were high-sensitivity troponin I (hs-TnI) levels, left ventricular ejection fraction (LVEF), and contrast-induced acute kidney injury (CI-AKI). Results: SGLT2i significantly reduced cardiovascular mortality risk versus other antidiabetic agents (hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.21–0.58, p < 0.0001). SGLT2i also lowered hs-TnI levels across all time points (mean difference: –2931 ng/L, p < 0.001). After adjustment for publication bias, this difference was no longer significant. However, peak hs-TnI levels remained significantly lower with SGLT2i (mean difference: –3836 ng/L, p < 0.001). Finally, SGLT2i improved LVEF versus comparators, with a mean difference of –5.00% (95% CI: –6.69 to –3.31, p < 0.001) at hospital discharge. SGLT2i was also associated with 60% lower odds of CI-AKI (odds ratio (OR): 0.40, 95% CI: 0.22–0.75, p = 0.004). Conclusions: Compared with other antidiabetic medications, SGLT2i may lower cardiovascular mortality, infarct size, and prevent left ventricle (LV) systolic dysfunction in diabetic patients with AMI undergoing PCI. The use of SGLT2i in this high-risk group is supported by these findings.

An Overview on Sodium-Glucose Cotransporter 2 (SGLT-2) Inhibitors Induced Euglycemic Diabetic Ketoacidosis: Clinical Manifestation, Mechanism, Diagnosis, Prevention and Treatment

Euglycemic diabetic ketoacidosis is a transient and dangerous metabolic condition characterized by ketoacidosis and considerably lower blood glucose levels which is associated with the usage of newer class of oral antidiabetic medication known as Sodium-glucose cotransporter 2 (SGLT-2) inhibitors. The primary mechanism involved in SGLT2 inhibitors induced eDKA would due to increased lipolysis and ketone body reabsorption. SGLT2i also tend to increase the pancreatic alpha cells, which simultaneously blocks the beta cells, thereby causing an disruption in glucagon/insulin ratio that accounts to enhanced lipolysis and ketogenesis, which is clinically manifested with Fatigueness, stomach pain, nausea and vomiting resulting in reduced blood pressure and dehydration, altered psychological condition, dyspnea, rapid breathing, loss of appetite, pyrexia and tachycardia. Despite lower blood glucose levels or the absence of urine ketones, euglycemic DKA is difficult to diagnose and should be examined in the differential diagnosis of an ill patient who as a previous history of diabetes mellitus. eDKA is often triggered by insulin absence or dose drop, severe acute sickness, dehydration, strenuous activity, surgeries, low-carbohydrate meals, or heavy alcohol or drug abuse. Making the definitive diagnosis using conventional diagnostic tools and clinical standards, as well as coordinating fluid resuscitation, insulin treatment, and electrolyte replacement based on information gained from prompt patient observing and knowledge of resolution criteria, are all components of management and the prevention method includes patient and physician education on risk and precipitating factors and suspending SGLT2 inhibitors therapy may reduce SGLT2 inhibitor-induced eDKA, which are more critical. This review briefly illustrates on the signs & symptoms, mechanism of induction, investigation and diagnosis, prevention and treatment of SGLT2 inhibitors-induced Euglycemic diabetic ketoacidosis (eDKA)

Methylene Blue in Metformin Intoxication: Not Just Rescue But Also Initial Treatment.

Metformin (MTF) is a widely used oral antidiabetic medication. Regardless the reason, high doses of MTF cause lactic acidosis as a result of its effects on mitochondrial ATP production and no-mediated vascular smooth muscle relaxation. Metformin-associated lactic acidosis can be life-threatening despite all treatments. Methylene blue (MB) has the potential to reverse the toxic effects of MTF through its effects on both the mitochondrial respiratory chain and nitric oxide production. The use of MB in MTF intoxication has only been reported in a limited number of cases. Herein, we present a 16-year-old female patient who attempted suicide by ingesting high doses of MTF. Supportive treatments, such as vasopressor, inotropic treatments, and sodium bicarbonate, were started in the patient who developed fluid-resistant hypotension after pediatric intensive care unit admission. Because of rising lactate levels, Continuous renal replacement therapy (CRRT) was started immediately. Despite all treatments, hypotension and hyperlactatemia persisted; MB was given as a rescue therapy. Noticeable hemodynamic improvement was observed within 30 minutes of initiating MB infusion, allowing a gradual decrease in the doses of inotropic infusions within the first hour of therapy. Patient's cardiovascular support was discontinued on the second day, and she was discharged on the fifth day. We speculate that, considering the mechanisms of MTF toxicity and the mechanisms of action of MB, it is suggested that early administration of MB, not only as a rescue treatment but as the initial approach to MTF poisoning in combination with other treatments, may result in improved outcomes.

Analysing Health Professionals' Adherence to National Guidelines and Comparing Diabetes Care in Specialized Care Centres and Hospitals

The socioeconomic impact of diabetes treatment includes significant costs for diagnosis, treatments, hospitalizations, and associated social challenges. According to the International diabetic federation (IDF) guidelines, effective management entails a holistic strategy including nutritious diet, avoiding carbonated beverages, quitting smoking, and routine exercising. Targeted weight loss is critical, comprising antidiabetic medications, a specific food plan, and lifestyle changes to attain a 7-8% glycated hemoglobin level. Proper medicine and footwear use reduces ulcer risks and further complications. The IDF emphasizes detailed treatment plans and sequential screenings. Diabetes management is obligatory, focusing glycaemic control, lifestyle changes, and risk assessment. A study examines treatment programs, medical behaviour, and factors impacting diabetic care reception. This study examined diabetes mellitus treatment in medical facilities by conducting health information reviews in outpatient clinics with a sample size of 400 records. Java applets detected problems, indicating 95% confidence in therapy. Cross-sectional studies in Peshawar hospitals included 250 patients, whereas specialized diabetic treatment centers evaluated 150 patients. Documented care differed; public hospitals had lower foot inspection rates (16.4%) than specialized care (14%). Statistical analysis, such as the Chung test and binary logistic regression, was used to assess variable relationships. Smoking was common (86%), and 59.8% relied on oral anti-diabetic medications. Less than 30% follow up examinations were recorded in public hospitals which showed discrepancies in documentation. Diabetes management can be improved, particularly through better screening procedures. Discrepancies between provided and documented care underscore the need for higher documentation standards. Private clinics demonstrated comparatively better care, possibly influenced by consultation fees, facility availability, and a comfortable environment—attributes lacking in public hospitals in Pakistan.

Evaluation of Anti-diabetic Drugs using ATC/DDD and DU90% Methods in Diabetes Mellitus Patients

Evaluation of Anti-diabetic Drugs using ATC/DDD and DU90% Methods in Diabetes Mellitus Patients

Greater persistence and adherence to basal insulin therapy is associated with lower healthcare utilization and medical costs in patients with type 2 diabetes: a retrospective database analysis

IntroductionWe aimed to assess persistence and adherence to basal insulin therapy, their association with all-cause healthcare resource utilization (HCRU) and direct medical costs, and predictors of persistence and adherence in...

Mid-Term Diabetes Remission Outcome in Patients with BMI ≤ 30kg/m2 Following Sleeve Gastrectomy.

Bariatric and metabolic surgery is recommended for Asian patients with type 2 diabetes mellitus (T2DM) and BMI ≥ 27.5kg/m2. However, mid to long-term ·evidence is still lacking. Patients' data that underwent laparoscopic sleeve gastrectomy (SG) as the primary surgery at the Affiliated Hospital of Xuzhou Medical University were analyzed. Patients with T2DM diagnosed with either fasting blood glucose (FBG) ≥ 7.0mmol/L or glycosylated hemoglobin (HbA1c) level ≥ 7.0% and 27.5 ≤ BMI ≤ 30kg/m2 were included. 24 patients (7 male and 17 female) were included in this study. With a mean follow-up duration of 4.5 ± 1.1years, the mean percentage of total weight loss (%TWL) was 14.4 ± 6.7%. Postoperatively, nine patients (37%) still required oral anti-diabetic medications, while no patients used insulin. FBG and HbA1c levels declined to 6.3 ± 1.5mmol/L and 6.0 ± 1.0%, respectively. Fifteen patients (63%) were with HbA1c levels < 7% and without medication requirements, five patients (21%) were with HbA1c levels < 7% with the help of oral anti-diabetic medication, and four patients (16%) were with HbA1c levels > 7% with the help of oral anti-diabetic medication. Our study provides further evidence that SG could result in both T2DM improvement and remission in patients with BMI ≤ 30kg/m2. Longer follow-up duration and larger sample will be needed in the future.

Continuation of Oral Antidiabetic Medications Was Associated With Better Early Postoperative Blood Glucose Control Compared to Sliding Scale Insulin After Total Knee Arthroplasty

BackgroundThis study evaluated blood glucose (BG), creatinine levels, metabolic issues, length of stay (LOS), and early postoperative complications in diabetic primary total knee arthroplasty (TKA) patients. It examined those who continued home oral antidiabetic medications and those who switched to insulin postoperatively. The hypothesis was that continuing home medications would lead to lower BG levels without metabolic abnormalities. MethodsPatients who had diabetes who underwent primary TKA from 2013 to 2022 were evaluated retrospectively. Diabetic patients who were not on home oral antidiabetic medications or who were not managed as an inpatient postoperatively were excluded. Patient demographics and laboratory tests collected preoperatively and postoperatively as well as 90-day emergency department visits and 90-day readmissions, were pulled from electronic records. Patients were grouped based on inpatient diabetes management: continuation of home medications versus new insulin coverage. Acute postoperative BG control, creatinine levels, metabolic abnormalities, LOS, and early postoperative complications were compared between groups. Multivariable regression analyses were performed to measure associations. ResultsA total of 867 primary TKAs were assessed; 703 (81.1%) patients continued their home oral antidiabetic medications. Continuing home antidiabetic medications demonstrated lower median maximum inpatient BG (180.0 mg/dL versus 250.0 mg/dL; P < .001) and median average inpatient BG (136.7 mg/dL versus 173.7 mg/dL; P < .001). Logistic regression analyses supported the presence of an association (odds ratio = 17.88 [8.66, 43.43]; P < .001). Proportions of acute kidney injury (13.5 versus 26.7%; P < .001) were also lower. There was no difference in relative proportions of metabolic acidosis (4.4 versus 3.7%; P = .831), LOS (2.0 versus 2.0 days; P = .259), or early postoperative complications. ConclusionsContinuing home oral antidiabetic medications after primary TKA was associated with lower BG levels without an associated worsening creatinine or increase in metabolic acidosis. Level III EvidenceRetrospective Cohort Study.

Brassica oleracea var.acephala of kashmir as a promising candidate for improvement of lipid profile associated with hyperglycemia through in vivo study in male albino rats

Diabetes mellitus commonly considered as clandestine killer is a metabolic disorder that affects people all over the world and is a silent killer. A variety of treatments are available, including insulin and oral anti-diabetic medications for regulating blood sugar levels in the body but every treatment option has certain unfavorable side effects that might cause abnormalities with the macro and microvascular systems in the human body. Kale (Brassica oleracea var. acephala) from the brassica family is gaining popularity due to its phytochemical content and ability to prevent many ailments, notably those brought on by oxidative stress. The current study assessed Brassica oleracea var acephala of the UT of Kashmir locally known as khanyari as it is loaded with various bioactive substances including total phenols, flavonoids, and glucosinolates that impart antioxidant and antidiabetic properties. Kale(K-29) showed impressive results in normalizing the blood glucose levels(102.30mg/dl) as well as improving the lipid profile such as cholesterol(76.22mg/dl), HDL(36.4mg/dl), LDL(36.1mg/dl), VLDL(21.2mg/dl) and triglycerides(85.40mg/dl) that is usually accompanied with hyperglycemia. The treatment of K-29 also showed improvisation in the various hepatic parameters such as S.G.P.T(91.14), S.G.O.T (41.18), Alkaline phosphatase (102.32U/L), Albumin (6.12g/dl), S. bilirubin direct(0.6mg/dl), S. bilirubin indirect(0.43mg/dl).

The association between antidepressant treatment and rates of insulin initiation in comorbid depression and type 2 diabetes: A UK electronic health record nested case-control study

AimsTo investigate the association between antidepressant prescribing and the rate of insulin initiation in type 2 diabetes. MethodsUsing UK primary care records we completed a nested-case control study in a individuals with comorbid depression and type 2 diabetes. Cases were defined as individuals initiating insulin, controls were individuals remaining on oral antidiabetic medication. We used conditional logistic regression to estimate incident rate ratios (IRR) and the 95% confidence intervals (CI) for the association between antidepressant prescribing and initiating insulin. We adjusted for demographic characteristics, comorbidities, health service and previous medication use. ResultsWe included 11,862 cases who initiated insulin, and 43,452 controls. Increased rates of insulin initiation were associated with any antidepressant prescription (IRR 3.78, 95% CI 3.53–4.04), longer (24+ months) durations of antidepressant treatment (IRR 5.61, 95% CI 5.23–6.03), and higher numbers (3+) of different antidepressant agents prescribed (IRR 5.72, 95% CI 5.25–6.24). There was no difference between recent and non-recent antidepressant prescriptions, or between different antidepressant agents. ConclusionsAntidepressant prescribing was highly associated with the initiation of insulin therapy. However, this may not indicate a direct causal effect of the antidepressant medication itself, and may be a marker of more severe depression influencing diabetic control.

Imeglimin: the New Kid on the Block.

This review aims to collect all the data regarding imeglimin and present it as one of the options for managing diabetes. It is a new drug that has recently been approved as an oral anti-diabetic drug, either as monotherapy or in combination with other oral antidiabetic drugs including insulin, with modest HbA1c reduction, and a fairly safe profile. Imeglimin was first approved in 2021 in Japan and China and is available in India from October 2022. Imeglimin is the first compound in a new class of oral anti-diabetic medications known as "glimins" that include a tetrahydrotriazine ring. Glimins act by amplifying glucose-stimulated insulin secretion (GSIS) and preserving β-cell mass, leading to augmented insulin secretion. Furthermore, It also intensifies insulin action by inhibiting of hepatic glucose output and recovery of altered insulin signalling in both hepatocytes (liver) and myocytes (skeletal muscle). This is a unique mode of action than has been demonstrated to be distinct from other classes of drugs, as it targets both insulin secretion and insulin resistance by correcting the mitochondrial dysfunction. Imeglimin has been studied in various phase III trials which have equivocally shown it to be effective in lowering glucose levels and improving pancreatic function and its recommended dose set at 1000 mg bid.

Effect of exercise in incident atrial fibrillation among diabetes mellitus with different diabetes duration

Abstract Background/Introduction In previous studies, level of exercise and AF risk seems to have nonlinear relationship. Vigorous physical activities have been considered as a risk factor of atrial fibrillation (AF). However, other studies have shown regular exercise to be associated with reduced incidence, symptoms, recurrence, and burden of AF. Conversely, a sedentary lifestyle is an important risk factor for the development of AF. Currently, the effect of exercise amount on the risk of AF among patients with diabetes mellitus (DM) according to diabetes duration has not been examined. Purpose This study aimed to evaluate the effect of exercise amount on incident AF among patients with DM using a nationwide population cohort. Methods The subjects with type 2 DM who underwent the Korean National Health Insurance Service health examination during 2015 and 2016 were identified. The study population was divided into four groups according to DM duration (new onset, less than 5 years, 5 to 10 years, and more than 10 years). Also, they were categorized into four groups according to the amount of exercise (0, &amp;lt;500, 500 to 1000, 1000-1500, and ≥1500 METs-Min per week). The study outcome was incident AF. Results A total of 2,392,486 subjects with a mean follow-up duration of 3.9 ± 0.9 years were enrolled (mean age 59.3 ± 12.0, female 39.8%). The mean DM duration was 5.3 ± 5.1 years, and the mean exercise amount was 643.0 ± 638.0 METs-min/week. 704,732 subjects were new-onset DM, 649,811 subjects had less than 5 years of DM duration, 464,870 subjects had DM duration between 5 to 10 years, and 573,073 subjects had more than 10 years of DM. As the DM duration became longer, age, the prevalence of comorbidities (hypertension, chronic kidney disease, chronic heart failure, prior myocardial infarction, prior stroke, and prior peripheral artery disease), the prevalence of more than three oral anti-diabetes medications, and insulin usage increased sequentially (all p&amp;lt;0.0001). In each DM duration group, the exercise amount of AF risk showed slightly different relationship. The new-onset DM group and DM duration 5 to 10 years groups showed the most reduced AF risk in exercise amounts 1000 -1500 METs-Min/week (adjusted hazard ratio [HR] 0.98, 95% confidence interval [CI] 0.82-0.96 p=0.0016 and adjusted HR 0.83, 95% CI 0.77-0.89, p=0.0098, respectively). The DM duration less than 5 years and more than 10 years groups both showed the lowest risk in exercise ≥1500 METs-Min/week (adjusted HR 0.91, 95% CI 0.85-0.97; adjusted HR 0.85, 95% CI 0.81-0.90, both p&amp;lt;0.001). Conclusions Regular exercise of more than ≥1500 METs-Min/week did not increase the risk of AF risk in DM patients. It was associated with reduced AF risk in all DM patients except new-onset DM. Further study is needed to assess the biophysiological change regarding DM duration that could affect the AF risk.

The effect of basic carbohydrate counting on HbA1c in type 2 diabetic patients: A non-randomized controlled trial

AimTo evaluate the effect of basic carbohydrate counting (CC) on HbA1c in Type 2 Diabetes (T2D) patients using oral antidiabetic drugs in the primary care. MethodThe study is a non-randomized controlled clinical trial. T2D patients, aged between 18 and 75 years, HbA1c ≥ 6,5 %, using oral antidiabetic medication, were followed for three months in two groups: one intervention (IG) (n = 33), one control group (CG) (n = 45), in two different Primary Care Centers. General diabetes care was applied in both groups; basic CC training was given additionally to the IG. An informative CC booklet was distributed to both groups. Beside sociodemographic questionnaire, CC knowledge scale was applied to all participants; HbA1c, other laboratory, anthropometric measurements were performed at the beginning and at the 3rd month of the study. ResultsAt the third month, HbA1c decreased within the IG from 7.7 % to 7.2 % (p:0.002), from 7.49 % to 7.46 %, in the CG (p:0.851). Comparing groups, the decrease in HbA1c in the IG was higher than in the CG (−0.5, −0.02, p: 0.018). Third month knowledge score was higher the IG’s (<0.001). ConclusionBasic CC training provided to T2DM patients, improves glycemic control by improving HbA1c and increasing CC knowledge.

Effects of metformin on parasitological, pathological changes in the brain and liver and immunological aspects during visceral toxocariasis in mice

There are currently insufficient anthelmintic medications available for the treatment of toxocariasis. For instance, Albendazole (ABZ) is the preferred medication, but its effectiveness against tissue-dwelling parasites is limited. In addition, Metformin (MTF) is a widely used oral antidiabetic medication that is considered to be safe for treatment. This study aimed to investigate any potential effects of MTF, alone or in combination with ABZ, on mice infections caused by Toxocara canis (T. canis). The efficacy of the treatment was assessed in the acute and chronic phases of the infection by larval recovery and histopathological, immunohistochemical, and biochemical studies. The results showed that combined therapy significantly reduced larval counts in the liver, brain, and muscles and ameliorated hepatic and brain pathology. It reduced oxidative stress and TGF-β mRNA expression and increased FGF21 levels in the liver. It decreased TNF-α levels and MMP-9 expression in the brain. In addition, it increased serum levels of IL-12 and IFN-γ and decreased serum levels of IL-4 and IL-10. In the acute and chronic phases of the infection, the combined treatment was more effective than ABZ alone. In conclusion, this study highlights the potential role of MTF as an adjuvant in the treatment of experimental T. canis infection when administered with ABZ.

THU275 Tacrolimus Levels And Kidney Function In Kidney Transplanted (KT) Patients With Diabetes On Glucagon Like-1 Receptor Agonists (GLP1-RA)

Abstract Disclosure: M.S. Campana: None. V. Kumar: None. D. Redden: None. H.J. Zelada Castro: None. Introduction: Uncontrolled Diabetes after solid-organ transplantation is associated with an increased risk of cardiovascular disease and renal graft loss. GLP1-RA are commonly used in the management of diabetes in non-transplanted populations because of cardio-metabolic benefits; however, their impact on tacrolimus absorption and kidney function in the post-transplant period has not been adequately studied. We aim to describe the association of blood tacrolimus levels, dose adjustments and kidney function in KT participants with diabetes who received GLP1-RA to participants who did not. Methods: We analyzed 50 adults with diabetes who underwent KT from 08/2020 to 08/2022 at UAB-Transplant Institute. 25 participants on insulin ± oral antidiabetic medications initiated GLP1RA (cases) and 25 participants on insulin ± oral antidiabetic did not start GLP1RA (controls). GLP1RA was started 7.72 months±5.26 after KT and 88% of them were on GLP1RA for the first time. Case group did not report active gastrointestinal symptoms and were educated to eat small-meal portions. We assessed number of times tacrolimus were at target [4-7 ng/ml], above or below target, number of times tacrolimus doses were adjusted, GFR and rejection rates (kidney biopsy) before GLP1RA therapy, 3 and 6 months after. For the comparison of categorical variables between groups, we used Pearson’s Chi-Square Test. Due to observed deviations from normality; we compared the distributions of counts and continuous outcomes between groups using Wilcoxon Rank Sum Tests. All tests were conducted using SAS 9.4. Results: KT participants (case, control) were predominantly of age (56.28 years, 57.40 years (p=0.66)), male (64%, 64% (p=1.0)), African American (60%, 84% (p=0.23)) and with a transplant rejection rate of 16% vs. 20% (p=0.71). There was a statistical difference in creatinine, GFR, and tacrolimus dose adjustments between the two groups. 1) Creatinine: Cases (at 6 months,1.48 mg/dL ± 0.41), Controls (at 6 months, 2.74 ± 2.38) (p=0.03). 2) GFR: Cases (at 6 months, 53.44 ml/min ± 15.89 ), Controls (at 6 months, 40.34 ± 17.75) (p=0. 038). 3) Number of Times Tacrolimus levels were out of range: Cases (at 3 months, 1.44 ± 1.08), Controls (at 3 months, 2.08 ± 0.81) (p= 0.02). 4) Number of times tacrolimus dose was increased: Cases (at 6 months, 0.12 ± 0.33), Controls (at 6 months, 0.36 ± 0.49) (p=0.04). None of the participants developed significant gastrointestinal side effects and the rate of GLP1RA discontinuation was 0%. Conclusion: Participants who took GLP1RA had better-preserved kidney function compared to those who did not, especially in the early post-kidney transplant period. Contrary to concern for altered tacrolimus absorption, patients treated with GLP1RA did not appear to have altered absorption requiring dose adjustment and can be used safely with minimal side effects and better efficacy compared to standard-of-care treatment. Presentation: Thursday, June 15, 2023

Long-term outcomes of laparoscopic sleeve gastrectomy in those with class I obesity: safety, efficacy, and quality of life.

Class I obesity carries significant morbidity and mortality risk similar to higher grades of obesity, and persons with class I obesity have a high risk of progression to class II and III obesity. While bariatric surgery has made strides in safety and efficacy, it remains inaccessible for persons with class I obesity (body mass index [BMI] of 30-35 kg/m2). To assess safety, weight loss durability, co-morbidity resolution, and quality of life after laparoscopic sleeve gastrectomy (LSG) in persons with class I obesity. Multidisciplinary medical center that specializes in obesity management. A longitudinal prospective single-surgeon registry was queried for data pertaining to persons with class I obesity who underwent primary LSG. Primary endpoint was weight loss. Secondary endpoints included change in obesity-related co-morbidities, adverse events, and post hoc analysis of symptoms of gastroesophageal reflux disease (GERD) and Bariatric Analysis and Reporting Outcome System results. Follow-up was divided into short- (1-3 yr), intermediate- (4-7 yr), and long-term (8-12 yr). We evaluated percent excess weight loss (%EWL) using linear mixed models adjusting for age, sex, years since operation, and baseline BMI. Least-squares means estimates and 95% confidence intervals (CI) were generated. Of 13,863 bariatric procedures, a total of 1851 patients were included. Mean baseline BMI, age, and male:female ratio were 32.6 ± 2.1 kg/m2, 33.7 ± 9.2 years, and 1:5, respectively. Adjusted mean %EWL (95% CI) at short-, intermediate-, and long-term follow-up were 111% (95% CI, 91%-131%), 110% (95% CI, 89%-131%), and 141% (95% CI, 57%-225%), respectively. Of 195 patients with type 2 diabetes, 59% experienced complete remission, and of 168 patients with hypertension, 43% experienced complete remission. Being on oral antidiabetes medication was a significant predictor of sustained remission compared with being on insulin or combination therapy (P < .001). Sixty-nine patients had symptoms of GERD before surgery, which improved in 55 (79.7%). Thirty-three patients developed de novo symptoms of GERD. The average Bariatric Analysis and Reporting Outcome System score was 4.5 ± 1.7, with 83% of participants rating their quality of life after surgery as good, very good, or excellent. Those with class I obesity who undergo LSG experience normalization of weight, sustained remission of co-morbidity, and good quality of life without significant risk of morbidity or mortality.

Beyond Syringes and Pills: Advances in Drug Delivery Systems for Diabetes

Diabetes is a chronic disease that affects millions of people worldwide, and its prevalence is increasing. The two primary subtypes, type 1 and 2, have different causes and mechanisms, but both result in abnormal glucose metabolism. The standard of care for diabetes includes insulin therapy, oral anti-diabetic medications, diet, exercise, weight loss, and frequent self-monitoring of blood glucose levels. However, these treatments have limitations that can lead to poor patient compliance and suboptimal outcomes. Alternative insulin delivery systems such as inhalers, patches, and oral sprays offer potential benefits such as increased convenience, reduced pain, and improved adherence. Non-insulin injectables, long-acting basal insulins, and GLP-1 agonists have also shown promise in improving glycemic control and reducing the risk of complications. Nanoparticle-based systems like SLNs are a novel approach that offers several advantages for diabetic management. They allow for targeted drug delivery, controlled release, and improved biocompatibility, enhancing drug efficacy and reducing side effects. SLNs have shown potential in animal models for reducing extracellular matrix degradation, inhibiting carbohydrate digestive enzymes, and enhancing the regeneration of insulin-producing beta cells. More studies are needed to validate their safety and efficacy in humans, but the potential benefits of SLNs make them a promising option for diabetes management.