Reduction In HbA1c Research Articles

Short-Term Impact of Digital Mental Health Interventions on Psychological Well-Being and Blood Sugar Control in Type 2 Diabetes Patients in Riyadh

Background: Type 2 diabetes (T2D) management is complicated by psychological factors, yet mental health interventions are not routinely integrated into diabetes care. This study investigated the impact of a digital mental health intervention on psychological well-being and glycemic control in T2D patients. Methods: A quasi-experimental study was conducted with 120 T2D patients divided into intervention (n = 60) and control (n = 60) groups. The intervention group received a one-month digital mental health intervention alongside standard care. Psychological well-being (PHQ-9, GAD-7, and DDS) and glycemic control (HbA1c) were assessed at baseline and post-intervention. Results: The intervention group showed significant improvements in HbA1c levels (−0.5%, p = 0.032), PHQ-9 (−3.1, p = 0.001), GAD-7 (−2.8, p = 0.006), and DDS (−7.7, p = 0.012) scores compared to the control group. Strong correlations were observed between psychological improvements and HbA1c reductions. Higher engagement with the digital platform was associated with greater improvements in both psychological and glycemic outcomes. Conclusions: Integrating digital mental health interventions into T2D care can significantly improve both psychological well-being and glycemic control. These findings support a more holistic approach to diabetes management that addresses both mental and physical health aspects.

Oral Semaglutide Use in Type2 Diabetes: A Pooled Analysis of Clinical and Patient-Reported Outcomes from Seven PIONEER REAL Prospective Real-World Studies.

Oral semaglutide is a glucagon-like peptide1 receptor agonist (GLP-1RA) approved for improving glycemic control in adults with type2 diabetes (T2D). The PIONEER REAL program evaluates clinical and patient-reported outcomes of oral semaglutide treatment as part of routine clinical practice across 13 countries. Here, data from Canada, Denmark, Italy, the Netherlands, Sweden, Switzerland, and the UK are pooled and analyzed to address treatment satisfaction as well as glycated hemoglobin (HbA1C) and body weight changes in relevant subgroup analyses. This pooled analysis encompasses seven country-specific, non-interventional, multicenter, phase4, prospective, single-arm clinical studies assessing the use of oral semaglutide in adults with T2D. Primary endpoint was the change in HbA1C from baseline to end of study (EOS), and secondary endpoints included changes in body weight and treatment satisfaction. For the analyses, results were stratified by age, T2D duration, and oral semaglutide dose at EOS as well as baseline HbA1C, body weight, and body mass index. Oral semaglutide treatment was initiated by 1615 participants. At EOS, 1222 (76%) participants out of the 1483 (92%) who completed the study were on treatment. Estimated changes in HbA1C and body weight from baseline to week38 were - 1.0%-point (95%CI - 1.08 to - 0.97; P < 0.0001) and - 5.0% (CI - 5.37 to - 4.72; P < 0.0001). Treatment satisfaction increased significantly during the study. Shorter T2D duration interacted with higher HbA1C reduction and body weight loss. Interaction was also observed between higher baseline HbA1C and more pronounced decrease in HbA1C. No significant interactions were detected between clinical outcomes and age or physician setting. The PIONEER REAL pooled analysis shows that people initiating oral semaglutide treatment experience improved glycemic control and body weight loss across age groups and T2D duration. This occurs regardless of specialist or primary care practice setting and is accompanied by an increased treatment satisfaction. NCT04559815 (Canada), NCT04537637 (Denmark), NCT05230615 (Italy), NCT04601740 (the Netherlands), NCT04601753 (Sweden), NCT04537624 (Switzerland), NCT04862923 (UK).

Abstract 4115652: Effect of the sodium-glucose co-transporter 2 inhibitor, Dapagliflozin, on ventricular repolarization electrocardiographic parameters: DAPA-ECG study

Background: In patients with type 2 diabetes (T2D), hyperglycemia and glycemic variability lead to prolongation and greater heterogeneity of ventricular repolarization, manifested on the electrocardiogram through an increase in QT, QTc, TpeakTend (TpTe) intervals and the TpTe/QT ratio, increasing the risk of potentially malignant arrhythmias. Dapagliflozin has demonstrated efficacy in reducing cardiovascular events in T2D patients and in the risk of serious ventricular arrhythmias and sudden cardiac death. However, the exact mechanisms by which dapagliflozin confers this protection have not yet been fully elucidated. Goals/Aims: The main objective of the study was to evaluate the impact of dapagliflozin on the TpTe interval of patients with T2D, and secondarily, it examined its impact on various electrocardiographic parameters such as the QT and QTc intervals, the TpTf/QT ratio, QT dispersion, J-T peak interval, QRS-T angle and heart rate. Methods: This randomized, prospective, multicenter and open-label study involved 174 patients with T2D, divided into two groups: one treated with dapagliflozin and the other with optimized medical therapy without iSGLT2. Clinical, electrocardiographic, laboratory and echocardiographic evaluations were carried out at the beginning and after three months. The statistical analysis included means, standard deviations, quartiles, and frequencies, with 95% confidence intervals, using Chi-square (or Fisher) and t-test (or Mann-Whitney) for initial differences, and a linear mixed-effects model to evaluate the results, adopting a significance level of 0.05. Results: The TpTe interval was significantly reduced in the dapagliflozin group from 76.87 ± 12.47 to 67.80 ± 10.34 (p&lt;0.001), and the QTc interval reduced from 424.07 ± 30.76 to 411.26 ± 25.31 (p=0.022). The TpTe/QT ratio in the dapagliflozin group was shortened from 0.20 ± 0.03 to 0.18 ± 0.02 (p&lt;0.001). Both groups showed reductions in mean blood glucose and HbA1c, with a greater decrease observed in the control group. No significant changes were recorded in other variables analyzed. Conclusion: In patients with T2D, dapagliflozin significantly reduced the duration of the TpTe and QTc intervals, in addition to the TpTe/QT ratio. These findings indicate a decrease in ventricular electrical remodeling with a potential cardioprotective effect of dapagliflozin, which would partly explain its benefits in reducing potentially malignant ventricular arrhythmias and sudden cardiac death.

Abstract 4137479: Integrating Ambulatory Care Pharmacists into Value-Based Primary Care: A Scalable Model for Addressing Cardiometabolic Disease

Background: Chronic disease is common, costly, and complicated. In the shift to value-based payment models, interventions to engage patients and improve disease control are necessary to reduce morbidity, mortality, and cost. The use of ambulatory pharmacists has demonstrated improved management of chronic diseases. Traditionally, ambulatory pharmacists are employed by healthcare systems. In this study, we test if integrating ambulatory pharmacists hired, trained, and managed by a retail pharmacy into value-based primary care (VBPC) clinics improves care. Hypothesis: Integrating a Walgreens pharmacist empowered by collaborative drug therapy management agreements (CDTM) into Village Medical (VMD) clinics will improve indicators of chronic disease control. Aims: Improve hemoglobin A1c (HbA1c) in patients with type 2 diabetes (T2D) and systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements in patients with hypertension (HTN). Methods: An ambulatory pharmacist was embedded into VMD clinics in Phoenix, Arizona under the supervision of VMD primary care providers via a CDTM. The pharmacist provided education, coaching, and medication management by prescribing and titrating therapies for treating T2D and HTN - enabled by access to pharmacy dispensing data. β was generated from difference-in-differences (DID) analyses with propensity score matched controls. Results: 125 patients had T2D, and 43 patients had HTN in the intervention group with 250 and 86 in the matched control group, respectively. The mean age was 65 years, 54% were female, 2% non-English speaking, and 29% racial/ethnic minorities. The average baseline HbA1c was 9% in the intervention group and 10% in the matched cohort. The average baseline SBP was 146 mmHg in the intervention group and 142 mmHg in the matched cohort. The β in the T2D group was -1.61% (p&lt;0.001) while the β in the HTN group was -10.2 mmHg (p&lt;0.01) for SBP and -2.0 mmHg (p=0.42) for DBP. Conclusion: We saw significant reductions in SBP and HbA1c in the pharmacist-managed group compared with matched controls. These results demonstrate that pharmacist integration into VBPC clinics may improve measures of chronic disease known to be associated with morbidity and mortality.

MECHANISMS OF ACTION OF PROTEIN SHAKES IN NORMALIZING METABOLIC PROCESSES, THEIR ROLE IN IMPROVING GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES, AND IN PREVENTING CARDIOVASCULAR DISEASES

This review article delves into the significance of protein shakes, particularly whey protein, in various health and fitness contexts. The primary focus is on their biochemical properties, metabolic benefits, and their role in supporting muscle mass, weight loss, and metabolic health. The article synthesizes findings from multiple studies to highlight the potential of protein shakes in improving glycemic control, reducing inflammation, and enhancing overall health, particularly for individuals with type 2 diabetes, obesity, and sarcopenia. The review also explores the effectiveness of protein shakes in athletic performance and recovery, as well as their impact on glucose metabolism and homeostasis. It underscores the necessity for further research to optimize the use and dosage of protein shakes for diverse populations to fully harness their benefits. Whey proteins are rich in essential amino acids, particularly leucine, which stimulates muscle protein synthesis via the mTOR pathway. This makes them highly effective in muscle building and recovery. Whey protein consumption enhances glycemic control by increasing insulin secretion and improving insulin sensitivity. Studies have shown significant reductions in fasting glucose levels and HbA1c in patients with type 2 diabetes. Protein shakes aid in weight loss by promoting satiety and increasing thermogenesis. They help maintain muscle mass during weight loss, which is crucial for sustaining metabolic rate. Clinical trials have demonstrated their efficacy in reducing body fat and improving metabolic markers. Whey protein, combined with resistance training, significantly improves muscle mass and strength in older adults, helping to prevent sarcopenia. This is essential for maintaining physical functionality and reducing the risk of falls and fractures. In the rehabilitation of patients with severe obesity, protein shakes are effective in reducing body weight, improving metabolic health, and maintaining muscle mass. They play a crucial role in comprehensive rehabilitation programs that include diet and physical exercise. Protein shakes support metabolic adaptations by preserving muscle mass and enhancing thermogenesis, which helps maintain a high metabolic rate and prevent weight regain. Whey proteins enhance muscle mass and strength, speed up recovery after training, and boost endurance. They also support the immune system and reduce oxidative stress, contributing to better overall athletic performance . Proteins shakes aid in regulating blood glucose levels and improving insulin sensitivity, which is crucial for preventing and managing diabetes. Their antioxidant and anti-inflammatory properties further enhance metabolic health.

Cardiovascular, Metabolic, and Safety Outcomes with Semaglutide by Baseline Age: Post Hoc Analysis of SUSTAIN6 and PIONEER6.

The high risk of cardiovascular events in people with type2 diabetes increases with age. The cardiovascular effects of once-weekly subcutaneous and once-daily oral semaglutide versus placebo in people with type2 diabetes at high cardiovascular risk were investigated in the SUSTAIN6 and PIONEER6 cardiovascular outcomes trials, respectively. It is unknown whether the effects of semaglutide are age dependent. This post hoc analysis evaluated cardiovascular, metabolic, and safety outcomes with semaglutide versus placebo in age subgroups (≤ 60; > 60 to ≤ 65; > 65 to ≤ 70; and > 70years) pooled from SUSTAIN6 and PIONEER6. Major adverse cardiovascular events (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke), changes from baseline in glycated hemoglobinA1c (HbA1c) and body weight, and adverse events were analyzed. Semaglutide reduced major adverse cardiovascular events and its components versus placebo across age subgroups (most hazard ratios < 1.0; pinteraction > 0.05). The treatment difference in HbA1c reduction was greater in those aged ≤ 60years than in older subgroups (pinteraction = 0.01). Reductions in body weight with semaglutide versus placebo were consistent across agesubgroups (pinteraction = 0.124). Serious adverse events or severe hypoglycemic episodes did not differ between semaglutide and placebo across age subgroups. Semaglutide consistently reduced major adverse cardiovascular events and body weight versus placebo across age subgroups; its safety profile did not differ with age. These results suggest that relaxing HbA1c targets based solely on age may not always be required for people with type2 diabetes. SUSTAIN6 (NCT01720446) and PIONEER6 (NCT02692716) are registered at ClinicalTrials.gov.

Benchmarking the medication efficiency and technological progress of diabetes drugs

BackgroundDiabetes poses a serious global challenge, given its increasing prevalence, detrimental effects on public health, and substantial economic burden. Since 1950s, tens of drugs have been approved by the United States (US) Food and Drug Administration (FDA). In the past decade, the medical community and regulatory agencies have moved away from the glucose-centric paradigm and increasingly call for a holistic approach to assess different treatments’ benefits and harms.ObjectiveThis study aimed to assess the medication efficiency and technological progress of Type 2 Diabetes (T2D) drugs, by considering their physiological outcomes, including both benefits (i.e., glucose lowering and weight loss) and adverse effects (mortality), relative to dosing frequency.MethodsTo derive medication efficiency, this study utilized data from the US FDA and prominent meta-analyses. Given that both the benefits and adverse effects of medications are multidimensional, this study employed a nonparametric frontier method, the data envelopment analysis (DEA) model, to integrate these factors into a measure of medication efficiency. Physiological outcomes could assume both positive and negative values. Adverse effects were regarded undesirable outputs. The DEA model was built under the framework of directional distance function and was able to handle negative and undesirable values which naturally arose in the case of T2D medications.ResultsThe paper presented a ranking of 20 T2D drugs in terms of medication efficiency. Three of them were able to attain the highest medication efficiency, all of which were in the GLP-1 class, including oral Semaglutide, subcutaneous Semaglutide and Dulaglutide. However, the other two GLP-1 drugs, Lixisenatide and Liraglutide, were less efficient. The average medication efficiency of drugs approved post-2010 was significantly higher than pre-2010 drugs. High dose frequency, low HbA1c reduction and insignificant weight loss were the main driving factors behind inefficiencies. Overall, medication efficiency provided an alternative perspective on treatment effectiveness other than conventional measures such as cost-effectiveness.

Real-World HbA1c Changes Among Type 2 Diabetes Mellitus Patients Initiating Treatment With a 1.0 Mg Weekly Dose of Semaglutide for Diabetes.

Background: Medical management of patients with type 2 diabetes mellitus (T2DM) is complex because of the chronic nature of the disease and its associated comorbidities. Injectable once-weekly semaglutide for diabetes (OW sema T2D) is a type of glucagon-like peptide-1 receptor agonist approved for the treatment of patients with T2DM. Objectives: To describe patient characteristics and HbA1c changes for patients prescribed 1.0 mg maintenance dose OW sema T2D. Methods: This retrospective study included adult patients with T2DM with a pre-index glycated hemoglobin (HbA1c) of at least 7%, initiating treatment with OW sema T2D between January 1, 2018, and December 31, 2019, and prescribed a 1.0 mg maintenance dose. Patients were identified in the Optum Research Database and were included if they had continuous health plan enrollment for at least 12 months prior to (pre-index) and at least 12 months following (post-index) the date of the first OW sema T2D claim (index). Dose at initiation and prescriber specialty were captured. Change in HbA1c between the latest post-index and pre-index HbA1c measurement was calculated among all patients and among those with at least 90 days of continuous treatment (persistent patients). Results: A total of 2168 patients were included in this study. On average, patients were taking 13.5 different classes of medications. The majority of patients had lipid metabolism disorder (90.8%), hypertension (86.6%), diabetes with complications (86.8%), or other nutritional/endocrine/metabolic disorders (72.5%). The mean HbA1c reduction was 1.2% (P < .001). Patients persistent with OW sema T2D (n =1280) had a mean HbA1c reduction of 1.4% (P < .001). The mean (SD) days covered with a 1.0 mg maintenance dose was 236.1 (94.1) days. Discussion: Despite being medically complex, the patients in this real-world study experienced significant reductions in HbA1c following initiation of OW sema T2D. Conclusions: A 1.0 mg maintenance dose of OW sema T2D is an effective treatment for T2DM in the real world.

Elucidating the role of weight loss and glycaemic control in patients with type 2 diabetes.

To investigate the independent contributions of glycated haemoglobin (HbA1c) reduction and weight loss to clinical outcomes in patients with type 2 diabetes (T2D) treated with antidiabetic drugs, including glucagon-like peptide-1 receptor agonists (GLP-1RAs). This observational, retrospective cohort study used deidentified electronic health record-derived data from patients evaluated at the Cleveland Clinic (1 January 2000-31 December 2020). Cohort A included 8876 patients with newly diagnosed T2D treated with any of six antidiabetic drug classes. Cohort B included 4161 patients with T2D initiating GLP-1RA treatment. The effects of body mass index (BMI) and HbA1c reduction, variability, and durability on clinical outcomes were investigated. In Cohort A, each 1% BMI reduction was associated with 3%, 1%, and 4% reduced risk of heart failure (p = 0.017), hypertension (p = 0.006), and insulin initiation (p = 0.001), respectively. Each 1% (~11 mmol/mol) HbA1creduction was associated with 4% and 29% reduced risk of hypertension (p = 0.041) and insulin initiation (p = 0.001), respectively. In Cohort B, each 1% BMI reduction was associated with 4% and 3% reduced risk of cardiovascular disease (p = 0.008) and insulin initiation (p = 0.002), respectively. Each 1% (~11 mmol/mol) HbA1c reduction was associated with 4% and 16% reduced risk of chronic kidney disease (p = 0.014) and insulin initiation (p = 1 × 10-4), respectively. Lower BMI variability and greater BMI durability were associated with decreased risk of clinical outcomes in both cohorts. Antidiabetic medication-associated, and specifically GLP-1RA-associated, weight loss and HbA1c reductions independently reduce real-world clinical outcome risk.

Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

This analysis evaluated the efficacy and safety of sotagliflozin, a dual SGLT1&2 inhibitor, added to insulin in patients with type 1 diabetes and chronic kidney disease (CKD). We used data from the 52-week pooled inTandem1&2 trials and the 24-week inTandem3 trial to assess the effects of sotagliflozin (200mg [inTandem 1&2 only] or 400mg daily) versus placebo on glycated hemoglobin (HbA1c; primary endpoint), body weight, systolic blood pressure (BP), insulin dose, and safety endpoints including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD. CKD was identified in 237/1575 of inTandem1&2 participants and 228/1402 of inTandem3 participants. At week-24, significant, placebo-adjusted reductions in HbA1c were observed - inTandem1&2: Non-CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.4 to -0.3; 400mg: -0.4%, 95% CI -0.5 to -0.3) and CKD subgroup (sotagliflozin 200mg: -0.4%, 95% CI -0.6 to -0.1; 400mg: -0.3%, 95% CI -0.5 to -0.1). For systolic BP, there was a significant reduction at week-24 with sotagliflozin in the non-CKD subgroup but no effect in the CKD subgroup in inTandem1&2. At week-52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared to placebo (17%) in the CKD subgroup of inTandem1&2, whereas the incidence of severe hypoglycemia was 5-6% across non-CKD subgroups. The incidence of adjudicated DKA at week-52 was 1%, 5%, and 3% for placebo, 200 mg, and 400 mg in the CKD subgroup compared to 0%, 3%, and 4% in the non-CKD subgroup. Results were generally similar in inTandem3 except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups. In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. Additionaly, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events.

Curalin supplement as add-on therapy for type 2 diabetes Mellitus

AimsTo examine the efficacy and safety of Curalin, as a supplement to anti-diabetic drugs (ADD). Methods135 patients were enrolled in the study. Among them, 109, ages 18–85 years, with HA1c 7.5–10 % under treatment with ADD were randomized 1:1 to receive Curalin supplement or placebo. The primary efficacy endpoint was the change in HbA1c after 3 months. The secondary endpoint was a decrease in HbA1c by more than 0.5 % and by more than 1 %. The exploratory endpoints included the Diabetes Treatment Satisfaction Questionnaire (DTSQ), clinical and laboratory results. ResultsAfter 3 months, the mean reduction in HbA1c was 1.30 % (SD = 0.79) in the Curalin group compared to 0.10 % (SD = 0.70) in the placebo group (P < 0.0001). A decrease in HbA1c of ≥ 0.5 % was observed in 90.0 % of Curalin patients versus 19.0 % of placebo patients (P < 0.0001). HbA1c reduction of ≥ 1 % occurred in 64.0 % of Curalin patients and 11.9 % of placebo patients (P < 0.0001). Curalin patients reported higher satisfaction (DTSQ) with no severe adverse events. ConclusionsCuralin treatment significantly reduced HbA1c over a period of 3 months and was well-tolerated.

Teleconsultation on patients with type 2 diabetes in the Brazilian public health system: a randomised, pragmatic, open-label, phase 2, non-inferiority trial (TELECONSULTA diabetes trial)

This study addresses the rising burden of type 2 diabetes mellitus, and explores the potential of teleconsultation, as an alternative for diabetes management. The primary objective was to test the hypothesis that teleconsultation is non-inferior to face-to-face consultation in terms of glycaemic control measured as glycated haemoglobin (HbA1c) (non-inferiority margin for the upper confidence interval for the difference between groups of 0,5% in HbA1c) for type 2 diabetes mellitus patients referred from Primary Healthcare to Specialized Care within the SUS. TELECONSULTA, is a randomized, pragmatic, phase 2, single-centre, open-label, non-inferiority trial conducted in Joinville, Brazil. A total of 278 participants diagnosed with type 2 diabetes were randomized through mandatory teleconsulting services from primary care health units. The randomization was 1:1 to teleconsultation or face to face consultation. The study was registered at the Brazilian Clinical Trial Register-REBEC, under the code RBR-8gpgyd. Study status is "Completed". This study included 278 participants in the intention-to-treat (ITT) analysis. The median age was 61 (54-68) years, 167 (60%) were women. The between-groups comparative average reduction in HbA1c was-0.6% (90% CI-1.0;-0.1) at 3-months and-0.5% (90% CI-0.9; 0.0) at 6-months in Modified Intention-to-Treat (mITT) population with imputed data, showing the non-inferiority of teleconsultation. Results with no missing data imputation and in the per protocol population were similar. The frequency of hypoglycaemia and other adverse events was well balanced between groups. The results underscore the transformative potential of telemedicine in addressing the complexities of diabetes management within the framework of a universal healthcare system, contributing with valuable insights for healthcare policymakers and practitioners seeking innovative solutions to tackle the growing diabetes epidemic. This study was funded by the Brazilian Ministry of Health, through the Unified Health System-Institutional Development Support Program (PROADI-SUS).

Real world effectiveness of oral semaglutide: Focus on patients with type 2 diabetes older than 75 years

AimData on the efficacy of oral semaglutide (OS) in elderly patients with type 2 diabetes are still lacking. This study evaluates the effectiveness of OS in a real world setting with a large ≥75 year old population. MethodsThis study includes all type 2 diabetic patients who started OS between October 2021 and December 2023 in seven diabetes centers. Data were collected at baseline, 6 (T6) and 12 (T12) months. Effectiveness measures were assessed on the total sample and by patient age (<65, 65–75, >75 years). ResultsOverall 1824 patients started OS, of those 18.7 % were over 75 years (>75 yr). OS resulted in a significant reduction in rate of patients using sulphonylureas, rapid and basal insulin therapy, HbA1c reduced by 0.87 % at T6 and at T12 (both p < 0.0001), body weight by 2.78 Kg (p < 0.0001) at T6 and 3.89 Kg (p < 0.0001) at T12. Similarly, >75 yr showed HbA1c reduction at T6 (p < 0.0001) and T12 (p = 0.0003), body weight significantly reduced (p for interaction 0.005) both at T6 (−1.57 Kg; p = 0.0003) and T12 (−2.74 Kg; p < 0.0001). ConclusionIn our study, OS results efficacy in non-elderly and elderly patients, making it an effective treatment option also for very elderly type 2 diabetic patients.

Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Type 1 Diabetes.

Background: GLP-1 receptor agonists (GLP-1RA) are used in the management of type II diabetes mellitus or obesity, although its role in patients with type I diabetes mellitus (T1DM) has been debated. This study aimed to investigate the efficacy and safety of GLP-1RA in patients with T1DM using real-world data. Methods: This multicenter, retrospective study was conducted at three tertiary medical centers in Riyadh, Saudi Arabia. The study followed up patients (>16 years old) with T1DM treated with insulin followed by GLP-1RA add-on therapy. The efficacy outcomes included changes in HbA1c, body weight, and insulin requirements from baseline to each follow-up visit. The main safety outcomes assessed included hypoglycemic events and gastrointestinal (GI) adverse events. Results: The study included 144 patients with a mean age of 33.0 ± 10.1 years. Semaglutide was the most used GLP-1RA (63.9%) followed by liraglutide (34.0%). From baseline to 3-month follow-up, HbA1c (mean difference (MD) = -0.8%; p = 0.0053), weight (MD = -2.4 kg; p = 0.0253), and daily basal insulin dose (MD = -2.1 units; p = 0.0349) were significantly reduced. Likewise, HbA1c (MD = -0.5%; p = 0.0004), weight (MD = -3.6 kg; p < 0.0001), and daily basal insulin (MD = -2.4 units; p = 0.0282) were significantly reduced at the 4-6-month follow-up. The significant reductions in HbA1c, weight, and daily basal insulin levels were consistent for up to 18-month follow-up. Only one patient had a major hypoglycemic event, whereas 8.3% of the patients had GI adverse events. Conclusions: Overall, significant improvements in glycemic control, weight loss, and insulin requirements were observed with the use of GLP-1RA in patients with T1DM, with a limited number of GI adverse events.

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

Twelve-months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with type 1 diabetes mellitus

Abstract Background Individuals diagnosed with type 1 diabetes mellitus (T1DM) exhibit indications of vascular and endothelial dysfunction earlier in comparison to healthy individuals. Evidence shows that SGLT-2 inhibitors (SGLT-2i) have a beneficial impact on cardiovascular health in individuals with type 2 diabetes mellitus (T2DM). We investigated the effects of dapagliflozin on endothelial and cardiovascular function in patients with T1DM. Methods We recruited in total 40 patients with T1DM and pour glycemic control who were treated with insulin and received dapagliflozin (n=20) or intensification of insulin treatment (n=20) (control group). We measured at baseline and at twelve months post-treatment the: a) Carotid-femoral pulse wave velocity (PWV-Complior; ALAM Medical) b) Central systolic blood pressure (cSBP) c) Perfused boundary region (PBR) of the sublingual arterial microvessels (marker of endothelial glycocalyx thickness) and d) Left ventricular global longitudinal strain (GLS) using speckle-tracking echocardiography. Results At baseline, patients among the two groups had similar age, sex, HbA1c and markers of endothelial and cardiovascular function (p&amp;gt;0.05). After 12 months of treatment, patients who received dapagliflozin displayed an improvement in PBR5–25 (−16%, p&amp;lt;0.05), in PWV (−9.3%, p&amp;lt;0.05), in cSBP (−6%, p&amp;lt;0.05) and in GLS (+4%, P&amp;lt;0.05) compared to baseline. However, no statistically significant changes in PBR5–25, in PWV, in cSBP and in GLS were observed after intensification of insulin treatment (PBR5–25: +0.4%, PWV: -1%, cSBP: −2%, GLS: −1% at 4 months, P&amp;gt;0.05), despite a similar HbA1c reduction (Table 1). Changes of PBR after one year treatment with dapagliflozin correlated with a concomitant reduction of PWV and cSBP (P&amp;lt;0.05). Conclusions Twelve months treatment with dapagliflozin improves endothelial glycocalyx and cardiovascular function in patients with T1DM, independently of glycemic control.

Beneficial Effects of a Freeze-Dried Kale Bar on Type 2 Diabetes Patients: A Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Type 2 diabetes (T2D) is one of the most common global diseases, with an ever-growing need for prevention and treatment solutions. Kale (Brassica oleracea L. var. acephala) offers a good source of fiber, minerals, bioavailable calcium, unsaturated fatty acids, prebiotic carbohydrates, vitamins, health-promoting secondary plant metabolites, as well as higher amounts of proteins and essential amino acids compared to other vegetables. The objective of this study was to investigate whether daily intake of freeze-dried kale powder can provide health benefits for T2D patients vs. placebo. This study was designed as a 12-week, blinded, randomized, controlled trial. Thirty T2D patients were randomly assigned to either a placebo bar (control) or a kale bar (intervention). Participants in the intervention group were instructed to consume three bars/day, each containing 26.25 g of freeze-dried kale (corresponding to approx. 341 g fresh kale/day). At baseline and 12 weeks, all participants underwent an oral glucose tolerance test (OGTT), 24 h blood pressure measurements, DEXA scans, and fasted blood samples were taken. A significant reduction in HbA1c, insulin resistance, body weight, and calorie intake was observed in the intervention group compared to control. Positive trends were detected in fasted blood glucose and LDL-cholesterol for those in the kale intervention group. No significant differences were found in total body fat mass and area under the curve glucose 240 min OGTT. Given the positive effects of high daily kale intake observed in this study, further research with a larger sample size is needed to better understand the health benefits of kale bars. This could potentially lead to new dietary recommendations for patients with T2D.

One-year outcomes of a digital twin intervention for type 2 diabetes: a retrospective real-world study

This retrospective observational study, building on prior research that demonstrated the efficacy of the Digital Twin (DT) Precision Treatment Program over shorter follow-up periods​​, aimed to examine glycemic control and reduced anti-diabetic medication use after one-year in a DT commercial program. T2D patients enrolled had adequate hepatic and renal function and no recent cardiovascular events. DT intervention powered by artificial intelligence utilizes precision nutrition, activity, sleep, and deep breathing exercises. Outcome measures included HbA1c change, medication reduction, anthropometrics, insulin markers, and continuous glucose monitoring (CGM) metrics. Of 1985 enrollees, 132 (6.6%) were lost to follow-up, leaving 1853 participants who completed one-year. At one-year, participants exhibited significant reductions in HbA1c [mean change: -1.8% (SD 1.7%), p < 0.001], with 1650 (89.0%) achieving HbA1c below 7%. At baseline, participants were on mean 1.9 (SD 1.4) anti-diabetic medications, which decreased to 0.5 (SD 0.7) at one-year [change: -1.5 (SD 1.3), p < 0.001]. Significant reductions in weight [mean change: -4.8 kg (SD 6.0 kg), p < 0.001], insulin resistance [HOMA2-IR: -0.1 (SD 1.2), p < 0.001], and improvements in β-cell function [HOMA2-B: +21.6 (SD 47.7), p < 0.001] were observed, along with better CGM metrics. These findings suggest that DT intervention could play a vital role in the future of T2D care.

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

Incidence and risk factors of post-metabolic and bariatric surgery hypoglycemia: a systematic review.

This study aimed to systematically review the existing literature to summarize the incidence and risk factors of post-metabolic and bariatric surgery hypoglycemia (MBSH). We searched PubMed, Medline, Embase, and the Cochrane Library databases for the studies published from inception to August 2023. Randomized controlled trials and analytical studies that investigated the incidence or risk factors of MBSH after different surgery techniques (including Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding, duodenal switch, omega-loop gastric bypass, and vertical banded gastroplasty) were involved. The incidence and risk factors of MBSH were extracted and described separately based on different diagnostic criteria and then summarized the risk factors and their statistical findings collectively. Twenty-nine studies were reviewed with follow-up ranging from 1 to 22 years. The incidence of MBSH ranged significantly across different diagnostic methods: 2.6-66.4% (self-report), 6.6-61.8% (oral glucose tolerance test), 29.4-78.6% (mixed-meal tolerance test), and 50-75% (continuous glucose monitoring). Patients with a mean age of 49.8 years and 89.0% of them were women with a better glycemic control who undergo RYGB and achieve 86.5% of estimated weight loss from surgery should be particularly vigilant about the possibility of developing MBSH. Distinct biomarkers such as IGF-1 (OR 1.06), fasting glicentin (AUC 0.81), HbA1c (AUC 0.76), and absolute weight reduction (AUC 0.72), greater fluctuations in glucose (OR 1.98) are valuable in promptly detecting MBSH. Specifically, patients with prior cholecystectomy or antidepressant therapy should be particularly cautious. The review highlights higher MBSH risk in younger women with significant weight loss after RYGB, and those with prior cholecystectomy or antidepressant use. Systematic summarization of MBSH criteria allowed us to identify the predictors for MBSH, which can aid in early diagnosis and treatment, reducing the need for prolonged monitoring.