Oral Glucose-lowering Medications Research Articles

Longitudinal associations of dietary fiber and its source with 48-week weight loss maintenance, cardiometabolic risk factors and glycemic status under metformin or acarbose treatment: a secondary analysis of the March randomized trial

AimsTo examine longitudinal and dose-d ependent associations between dietary fiber intake and various clinical outcomes over 48 weeks of pharmacological treatment in T2DM patients.MethodsIn this secondary analysis, we used data from the MARCH trial, which was designed to compare the efficacy of acarbose or metformin monotherapy as the initial therapy in Chinese patients newly diagnosed with T2DM. Dietary data were obtained using a 24-h dietary recall method to evaluate the intakes of dietary fiber from different sources as well as the carbohydrate-to-fiber ratio.ResultsA total of 551 newly-diagnosed patients with T2DM complete dietary records (286 in the acarbose group and 265 in the metformin group) were included. Higher intake of total fiber and whole grain fiber was positively associated with better β‐cell function, insulin sensitivity and postprandial glycemic control under acarbose treatment. Higher intake of legume fiber was associated with better glycemic control under both acarbose and metformin treatment but with better weight loss only under metformin treatment. A high-carbohydrate–low-fiber diet was associated with worse glycemic control and lower HDL-C under acarbose treatment but with higher insulin sensitivity and better weight loss under metformin treatment.ConclusionsThe notable effects of various dietary fibers when combined with different oral glucose-lowering medications should be considered to maximize therapeutic benefit.

A Randomized Crossover Study Comparing the Effects of Diabetes-Specific Formula with Common Asian Breakfasts on Glycemic Control and Satiety in Adults with Type 2 Diabetes Mellitus

Postprandial hyperglycemia was shown to be an independent risk factor for microvascular and macrovascular complications in type 2 diabetes mellitus (T2D). We aimed to investigate the glucose, insulin, and subjective appetite at 0, 15, 30, 45, 60, 90, 120, 150, and 180 min of three treatments: diabetes-specific formula (DSF), noodle soup, and glutinous rice. This was a randomized, crossover study with a one-week interval between treatments. Sixty-four T2D adults with oral glucose-lowering medication and HbA1c between 7% and <10% were randomized. The glucose positive area under the curve from 0 to 180 min (pAUC) was significantly lower with DSF than with glutinous rice (LSM ± SE: DSF 354 ± 32 vs. glutinous rice 451 ± 32 mmol.min/L, p = 0.033). The insulin pAUC was significantly lower with DSF (median [IQR]: 2733 [1542, 4204]) compared to glutinous rice (3359 [2193, 4744] µIU.min/mL), p = 0.042). The insulinogenic index at 30 min was significantly higher in DSF (median [IQR], 8.1 [4.2, 19.7]) compared to glutinous rice (5.4 [2.7, 11.7], p < 0.001). No significant differences were found in subjective appetite between the three treatments (all, p ≥ 0.827). There were also no significant differences in hunger, fullness, desire to eat, and prospective consumption ratings between DSF and the other two breakfasts (all p ≥ 0.181). Noodle soup led to the shortest time for hunger to return to baseline (165 min), 21 min earlier than DSF (186 min) and 32 min earlier than glutinous rice (197 min). DSF significantly reduced postprandial glucose and insulin responses compared with glutinous rice and had a higher satiating value than noodle soup in T2D adults. Replacing common Asian breakfasts with DSF may improve glycemia and hunger control.

Structured diabetes care routines in cardiac rehabilitation are associated with increased diabetes detection and improved treatment after myocardial infarction: a nationwide observational study

BackgroundDespite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI.MethodsCenter-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI.ResultsRoutine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014).ConclusionsHaving structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.

Prevalence of latent autoimmune diabetes in adults and insulin resistance: a systematic review and meta-analysis.

Latent autoimmune diabetes in adults is a form of diabetes that progresses slowly and is controlled by diet and oral glucose-lowering medications before insulin is required. The aim of the present study was to evaluate the prevalence of latent autoimmune diabetes in adults. The present study was conducted based on PRISMA 2020-27-item checklist. To find the studies conducted in line with the purpose of the study, PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase databases and Google Scholar search engine were reviewed from 2013 to August 2023. Meta-analysis was performed using effect size with 95% confidence interval. Data analysis was done using STATA/MP. v17 software. The present study was carried out based on the PRISMA 2020 27-point checklist. To find out which studies were carried out in accordance with the purpose of the study, from 2013 to August, the databases PubMed, Web of Science, Scopus, Science Direct, Web of Knowledge, EBSCO, Wiley, ISI, Elsevier, Embase and the search engine Google Scholar reviewed 2023. Meta-analysis was performed using effect size with 95% confidence interval. Data analysis was carried out using STATA/MP. v17 software. The overall prevalence of Latent autoimmune diabetes of adults was found to be 7% (95%CI 0-20). Subgroup analysis of Latent autoimmune diabetes of adults in the context of geographic regions showed a higher prevalence in North America (15%) and South East Asia (5%). Since the identification of Latent autoimmune diabetes of adult patients with other forms of diabetes is misdiagnosed due to the combination of phenotypic features with T1D and T2D, studying its prevalence is of great importance.

Precision Diabetes Education and Support Considering Patients' Behavioral and Psychological Phenotype: A Q-Methodology Study.

The prevalence of type 2 diabetes is growing, and diabetes burden is increasing. Precision health in diabetes education and support employs different intervention strategies, depending on an individual's viewpoint on diabetes and self-management behaviors, to improve patients' treatment adherence, clinical outcomes, and quality of life. To classify the behavioral and psychological phenotypes of self-management behaviors in adults taking oral glucose-lowering medications to develop a theory-driven, person-centered group intervention applicable to busy clinical settings. Q-methodology was used. From January to August 2020, 73 participants (48 male, 25 female) were invited to do Q-sorting with 33 statements. The principal component technique, followed by varimax rotation, was used for factor analysis. The Summary of Diabetes Self-Care Activity questionnaire and HbA1c in the past 6 months were included to obtain comprehensive understanding. Fifty-one sorts (35 male, 16 female) loaded on 1 of 4 factors: factor A (n = 18): Needing emotional support with enhancing problem-solving skills group; factor B (n = 15): Self-help group; factor C (n = 6): Needing personalized coaching group; and factor D (n = 12): Needing basic diabetes education group. Each factor demonstrated a different need for diabetes education and support. Younger participants (factor D) had the poorest diabetes self-management behaviors and required basic diabetes education. Further research is warranted to develop a screening tool to classify the typologies and adopt the findings in a busy clinical setting.

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.

Metformin hydrochloride: The most prescribed treatment for type II diabetes -gets banned

Metformin hydrochloride (MH) is synthesis of N, N-dimethylguanidine medicament which is used for the treat of type-II diabetes which was discovered by Emil Werner and James Bell, which belongs to BCS class III. MH is chosen first-line oral blood glucose-lowering medication for the treatment of type-II diabetes, almost around 120 million patients are using worldwide. It works by decreasing the hepatic glucose production through a mild inhibition of mitochondrial respiration chain complex. MH which has been further tested and also proven that it can be used for various treatments such as, weight loss, improving fertility, slow the growth of tumour, anti-malaria, and few others. MH is synthesis from Galega officinalis which is a perennial plant that blooms in the summer and is native to most temperate areas. In this study, complete information about the drug history, drug profile, pharmacokinetic, drug interaction, clinical symptoms, advantages & disadvantages of MH and reason why its getting banned has been explained in detail.

Omentin associates with serum metabolite profiles indicating lower diabetes risk: KORA F4 Study

IntroductionCirculating omentin levels have been positively associated with insulin sensitivity. Although a role for adiponectin in this relationship has been suggested, underlying mechanisms remain elusive. In order to reveal the...

A review on vitamin B12 deficiency induced by metformin

Multiple studies have established a higher prevalence of vitamin B12 deficiency in patients who have type 2 diabetes mellitus (T2DM). Metformin is prescribed as the 1st line oral glucose-lowering medication for individuals with T2DM. However, metformin therapy has been linked to vitamin B12 malabsorption, which can result in both biochemical and clinical manifestations of vitamin B12 deficiency. The long-term use of metformin is associated with a significant decrease in vitamin B12 levels, particularly in doses greater than 2000 mg per day over a period of 4 years. Vitamin B12 is a water-soluble vitamin. It acts as a cofactor for enzymes involved in DNA synthesis and neuroprotection at the cellular level. Hence, vitamin B12 deficiency can lead to various clinical consequences, including hematologic abnormalities such as megaloblastic anemia and hypersegmented neutrophil formation, peripheral neuropathy, and progressive axonal demyelination, hyperhomocysteinemia (HHcy). The latest "standards of medical care in diabetes-2017" issued by the American diabetes association recommends periodic assessment of B12 status and, if necessary, the use of B12 replacement therapy in diabetic patients taking metformin. In order to address the vitamin B12 deficiency associated with metformin several therapies are available including prophylactic supplements of calcium and vitamin B12, discontinuation of metformin, and replenishment of vitamin B12 stores through intramuscular or oral therapy. It is important to regularly monitor vitamin B12 levels for at least annually to prevent complications of vitamin B12 deficiency and continue with supplementation if metformin is still being used.

Encyclopaedic Review of Glipizide Pre-clinical and Clinical Status.

Glipizide is an oral glucose-lowering medication that is beneficial for the treatment of type 2 diabetes. This study compiles exhaustively all accessible information on glipizide, from preclinical to clinical studies. Glipizide may be used in concert with TRAIL to treat cancer cells; in vitro studies have shown that it suppresses angiogenesis and vasculogenesis while shielding cells from glycation-induced damage. Anticonvulsant effects and modifications in the pharmacokinetics of other medications, such as Divalproex Sodium, were seen in glipizide in vivo experiments. Propranolol amplifies glipizide's hypoglycemic effect briefly in normal animals but consistently enhances it in diabetic ones. In the treatment of cancer and neurodegenerative poly(Q) illnesses, glipizide has demonstrated to offer potential therapeutic advantages. It is ineffective in preventing DENA-induced liver cancer and may cause DNA damage over time. The way glipizide interacts with genetic variants may increase the risk of hypoglycemia. Combining Syzygium cumini and ARBE to glipizide may enhance glycemic and lipid control in type 2 diabetes. Individuals with coronary artery disease who take glipizide or glyburide have an increased risk of death. The risk of muscular responses and acute pancreatitis is minimal when glipizide and dulaglutide are combined. In conclusion, glipizide has shown promising therapeutic efficacy across a variety of disorders.

Tirzepatide: A Review in Type 2 Diabetes.

Tirzepatide (Mounjaro®), a first-in-class dual incretin agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, is approved for use as an adjunct to diet and exercise to improve glycaemic control in adults with type 2 diabetes mellitus (T2DM) in the USA, EU, Japan and other countries. It comes as single-dose prefilled pens and single-dose vials. In phase III SURPASS trials, once-weekly subcutaneous tirzepatide, as monotherapy or add-on-therapy to oral glucose-lowering medications and insulin, was superior to the GLP-1 receptor agonists (RAs) dulaglutide 0.75mg and semaglutide 1mg as well as basal and prandial insulin for glycaemic control and weight loss in adults with inadequately controlled T2DM. Tirzepatide was generally well tolerated, with a safety profile consistent with that of GLP-1 RAs. Tirzepatide was associated with a low risk of clinically significant or severe hypoglycaemia and no increased risk of major adverse cardiovascular events. Adverse events were mostly mild to moderate in severity, with the most common being gastrointestinal events including nausea, diarrhoea, decreased appetite and vomiting. In conclusion, tirzepatide is a valuable addition to the treatment options for T2DM.

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

The exact pathophysiological mechanisms of SGLT-2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT-2 inhibitors have potential anti-proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT-2 inhibitor drugs limit the generalizability of pre-clinical studies. This is a narrative review discussing the potential anti-cancer effects of SGLT-2 inhibitors, an oral glucose-lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre-clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT-2 inhibitors in cancer treatment. Type II diabetes is linked to various comorbidities and malignancies, but some glucose-slowering medications may have a preventive role in cancer. The use of SGLT-2 inhibitors was associated with bladder cancer based on mice studies. However, meta-analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT-2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti-cancer effects of doxorubicin. Combining SGLT-2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT-2 inhibitors in various types of cancer. More large-scale pre-clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT-2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre-clinical and clinical data regarding the potential anti-cancer effects of SGLT-2 inhibitors including the hypothetical pathophysiological mechanisms.

For adults with type 2 diabetes mellitus fasting during Ramadan, how do different oral glucose-lowering medications compare with sulfonylureas?

For adults with type 2 diabetes mellitus fasting during Ramadan, how do different oral glucose-lowering medications compare with sulfonylureas?

Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy

ObjectivesMany people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an...

Type 2 Diabetes Mellitus and Efficacy Outcomes from Immune Checkpoint Blockade in Patients with Cancer.

No evidence exists as to whether type 2 diabetes mellitus (T2DM) impairs clinical outcome from immune checkpoint inhibitors (ICI) in patients with solid tumors. In a large cohort of ICI recipients treated at 21 institutions from June 2014 to June 2020, we studied whether patients on glucose-lowering medications (GLM) for T2DM had shorter overall survival (OS) and progression-free survival (PFS). We used targeted transcriptomics in a subset of patients to explore differences in the tumor microenvironment (TME) of patients with or without diabetes. A total of 1,395 patients were included. Primary tumors included non-small cell lung cancer (NSCLC; 54.7%), melanoma (24.7%), renal cell (15.0%), and other carcinomas (5.6%). After multivariable analysis, patients on GLM (n = 226, 16.2%) displayed an increased risk of death [HR, 1.29; 95% confidence interval (CI),1.07-1.56] and disease progression/death (HR, 1.21; 95% CI, 1.03-1.43) independent of number of GLM received. We matched 92 metformin-exposed patients with 363 controls and 78 patients on other oral GLM or insulin with 299 control patients. Exposure to metformin, but not other GLM, was associated with an increased risk of death (HR, 1.53; 95% CI, 1.16-2.03) and disease progression/death (HR, 1.34; 95% CI, 1.04-1.72). Patients with T2DM with higher pretreatment glycemia had higher neutrophil-to-lymphocyte ratio (P = 0.04), while exploratory tumoral transcriptomic profiling in a subset of patients (n = 22) revealed differential regulation of innate and adaptive immune pathways in patients with T2DM. In this study, patients on GLM experienced worse outcomes from immunotherapy, independent of baseline features. Prospective studies are warranted to clarify the relative impact of metformin over a preexisting diagnosis of T2DM in influencing poorer outcomes in this population.

Association of sulfonylureas with the risk of dementia: A population-based cohort study.

Sulfonylureas are oral glucose-lowering medications positioned as a second-line therapy for type 2 diabetes. Evidence relating them to cognitive decline has been mixed. The objective was to determine whether sulfonylurea use was associated with a differential risk of dementia compared with dipeptidyl peptidase-4 (DPP4) inhibitor use. Using administrative data from residents in Ontario, Canada, adults aged ≥66 years who were new users of a sulfonylurea or a DPP4 inhibitor from June 14, 2011, to March 31, 2021 entered this population-based retrospective cohort study. Dementia was ascertained using a validated algorithm for Alzheimer's disease and related dementias. Propensity-score weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and confidence intervals (CI) for time to incident dementia. The observation window started at 1 year after cohort entry to mitigate protopathic bias due to delayed diagnosis. The primary analysis used an intention-to-treat exposure definition. A separate propensity-score weighted analysis was conducted to explore within-class differences in dementia risk among sulfonylurea new users selected from the primary cohort. Among 107,806 DPP4 inhibitor new users and 37,030 sulfonylurea new users, sulfonylureas compared with DPP4 inhibitors were associated with a higher risk of dementia (18.4/1000 person-years; aHR [95% CI] = 1.09 [1.04-1.15]) over a mean follow-up of 4.82 years from cohort entry. Glyburide compared to gliclazide exhibited a higher dementia risk (aHR [95% CI] = 1.17 [1.03-1.32]). New use of a sulfonylurea especially glyburide was associated with a higher dementia risk compared with new use of a DPP4 inhibitor in older adults with diabetes.

Association of Medication Adherence With HbA1c Control Among American Indian Adults With Type 2 Diabetes Using Tribal Health Services.

To examine HbA1c levels and adherence to oral glucose-lowering medications and their association with future HbA1c levels among American Indian adults with type 2 diabetes (T2D) receiving medications at no cost from a tribal health care system. Tribal citizens with T2D who used Choctaw Nation Health Services Authority (CNHSA) and Pharmacies and had HbA1c data during 2017-2018 were included in this study. Medication adherence (proportion of days covered [PDC] ≥0.80) was calculated using 2017 CNHSA electronic health record data. Of the 74,000 tribal citizens living on tribal lands, 4,560 were eligible; 32% had HbA1c at or below target (≤7%), 36% were above target (>7 to ≤9%), and 32% were uncontrolled (>9%) in 2017. The percentage of patients with PDC ≥0.80 was 66% for those using biguanides, 72% for sulfonylureas, 75% for dipeptidyl peptidase 4 inhibitors, and 83% for sodium-glucose cotransporter 2 inhibitors. The proportion of patients with HbA1c at or below target increased slightly from 32% in 2017 to 42% in 2018. Higher average PDC in 2017 was associated with lower HbA1c levels in 2018 (β = -1.143; P < 0.001). Medication adherence was higher than that found in previous studies using self-report methods in American Indian populations, although a smaller proportion of patients had HbA1c at or below target relative to U.S. adults with T2D. Medication adherence was associated with improved HbA1c levels for most oral glucose-lowering medication classes. Future studies of American Indians should use both longitudinal prescription data from both electronic health records and pharmacy refills.

Perioperative management of diabetes in patients undergoing bariatric and metabolic surgery: a narrative review and the Cleveland Clinic practical recommendations.

Bariatric and metabolic surgery is an effective treatment for patients with severe obesity and obesity-related diseases. In patients with type 2 diabetes, it provides marked improvement in glycemic control and even remission of diabetes. In patients with type 1 diabetes, bariatric surgery may offer improvement in insulin sensitivity and other cardiometabolic risk factors, as well as amelioration of the mechanical complications of obesity. Because of these positive outcomes, there are increasing numbers of patients with diabetes who undergo bariatric surgical procedures each year. Prior to surgery, efforts should be made to optimize glycemic control. However, there is no need to delay or withhold bariatric surgery until a specific glycosylated hemoglobin target is reached. Instead, treatment should focus on avoidance of early postoperative hyperglycemia. In general, oral glucose-lowering medications and noninsulin injectables are not favored to control hyperglycemia in the inpatient setting. Hyperglycemia in the hospital is managed with insulin, aiming for perioperative blood glucose concentrations between 80 and 180 mg/dL. Following surgery, substantial changes of the antidiabetic medication regimens are common. Patients should have a clear understanding of the modifications made to their treatment and should be followed closely thereafter. In this review article, we describe practical recommendations for the perioperative management of diabetes in patients with type 2 or type 1 diabetes undergoing bariatric surgery. Specific recommendations are delineated based on the different treatments that are currently available for glycemic control, including oral glucose-lowering medications, noninsulin injectables, and a variety of insulin regimens.

A randomized placebo-controlled clinical trial for pharmacological activation of BCAA catabolism in patients with type 2 diabetes

Elevations in plasma branched-chain amino acid (BCAA) levels associate with insulin resistance and type 2 diabetes (T2D). Pre-clinical models suggest that lowering BCAA levels improve glucose tolerance, but data in humans are lacking. Here, we used sodium phenylbutyrate (NaPB), an accelerator of BCAA catabolism, as tool to lower plasma BCAA levels in patients with T2D, and evaluate its effect on metabolic health. This trial (NetherlandsTrialRegister: NTR7426) had a randomized, placebo-controlled, double-blind cross-over design and was performed in the Maastricht University Medical Center (MUMC+), the Netherlands, between February 2019 and February 2020. Patients were eligible for the trial if they were 40–75years, BMI of 25–38 kg/m², relatively well-controlled T2D (HbA1C < 8.5%) and treated with oral glucose-lowering medication. Eighteen participants were randomly assigned to receive either NaPB 4.8 g/m²/day and placebo for 2 weeks via controlled randomization and sixteen participants completed the study. The primary outcome was peripheral insulin sensitivity. Secondary outcomes were ex vivo muscle mitochondrial oxidative capacity, substrate oxidation and ectopic fat accumulation. Fasting blood samples were collected to determine levels of BCAA, their catabolic intermediates, insulin, triglycerides, free fatty acids (FFA) and glucose. NaPB led to a robust 27% improvement in peripheral insulin sensitivity compared to placebo (ΔRd:13.2 ± 1.8 vs. 9.6 ± 1.8 µmol/kg/min, p = 0.02). This was paralleled by an improvement in pyruvate-driven muscle mitochondrial oxidative capacity and whole-body insulin-stimulated carbohydrate oxidation, and a reduction in plasma BCAA and glucose levels. No effects were observed on levels of insulin, triglycerides and FFA, neither did fat accumulation in muscle and liver change. No adverse events were reported. These data establish the proof-of-concept in humans that modulating the BCAA oxidative pathway may represent a potential treatment strategy for patients with T2D.

1205-P: Trends in Insulin Use and Glycemic Control in U.S. Adults with Diabetes, 1988–2020

Introduction: Insulin remains a last line therapy for type 2 diabetes, and formulations have improved significantly over the past 30 years. It is unknown whether these advancements have translated into better glycemic control in persons with diabetes. Methods: We conducted a trends analysis of cross-sectional data from the National Health and Nutrition Examination Survey (NHANES, 1988-2020) . Our analysis included 8,658 nonpregnant adults aged ≥20 with diagnosed diabetes. We examined trends in self-reported diabetes medication use (insulin or oral) and glycemic control (A1c&amp;lt;7.0%) , overall and by race/ethnicity. Results: From 1988-1994 to 2013-2020, there was an increase in the proportion of US adults with diabetes using only oral glucose-lowering medications (43.5% to 55.2%, p=0.003) . The proportion of patients using insulin did not change over the same period (30.5% to 28.2%, p=0.81) . Glycemic control improved among users of oral medications (p&amp;lt;0.001) (Figure 1a) . Among insulin users, glycemic control was unchanged (p=0.87) . Mexican American insulin users had a decrease in glycemic control (25.1% in 1988-94 to 9.9% in 2013-20, p=0.004) and had poorer glycemic control, overall, as compared to their non-Hispanic White or Black counterparts (Figure 1b-1d) . Conclusions: Despite improvements in insulin formulations, insulin users have not seen improved glycemic control. Disclosure S.Venkatraman: None. E.Selvin: Other Relationship; Wolters Kluwer. M.Fang: n/a.