Reduction In HbA1c Levels Research Articles

Investigation on Anti-diabetic Efficacy of a Cucurbitaceae Food Plant from the North-East Region of India: Exploring the Molecular Mechanism through Modulation of Oxidative Stress and Glycosylated Hemoglobin (HbA1c).

The medicinal plants of the Cucurbitaceae family, such as Solena heterophylla Lour. fruits, have significant ethnobotanical value and are readily accessible in North East India. We conducted a study on Solena heterophylla Lour. fruits to evaluate their anti-diabetic activity in vivo, standardize their HPTLC, and profile their metabolites using LC-QTOF-MS. We aimed to explore the molecular mechanism behind their effects on oxidative stress and glycosylated hemoglobin (HbA1c). Firstly, the ethyl acetate fraction of Solena heterophylla Lour. fruits was standardized using Cucurbitacin B as a standard marker by conducting HPTLC evaluation. Next, we delved into analyzing metabolite profiling. In addition, the standardized fraction was utilized in an experimental study to investigate the molecular mechanism of action in an in vivo high-fat diet and a low dose of streptozotocin-induced diabetic model. We have reportedly identified 52 metabolites in the ethyl acetate fraction of Solena heterophylla (EASH). In the in vitro tests, it has been observed that this extract from plants possesses notable inhibitory properties against α-amylase and α-glucosidase. Solena heterophylla fruits with high levels of Cucurbitacin B (2.29% w/w) helped lower FBG levels in animals with EASH treatment. EASH treatment reduced HbA1c levels and normalized liver lipid peroxidation and antioxidant enzyme levels. SGOT, SGPT, and SALP serum enzyme levels also returned to normal. Based on the current evaluation, it was found that EASH exhibited encouraging hypoglycemic effects in diabetic rats induced by a low dose of STZ and high-fat diet, which warrants further investigation.

Efficacy and Safety of Omarigliptin, a Novel Once-Weekly Dipeptidyl Peptidase-4 Inhibitor, in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

No recent meta-analysis has holistically analyzed and summarized the efficacy and safety of omarigliptin in type 2 diabetes mellitus (T2DM). We conducted a meta-analysis to address this knowledge gap. Electronic databases were searched to identify randomized controlled trials (RCTs) that included patients with T2DM who received omarigliptin in the intervention arm. The control arm consisted of either a placebo (passive control group [PCG]) or an active comparator (active control group [ACG]). The primary outcome assessed was changes in hemoglobin A1c (HbA1c), while secondary outcomes included variations in glucose levels, achievement of glycemic targets, adverse events (AEs), and hypoglycemic events. From 332 initially screened articles, data from 16 RCTs involving 8,804 subjects were analyzed. Omarigliptin demonstrated superiority over placebo in reducing HbA1c levels (mean difference, -0.58%; 95% confidence interval, -0.75 to -0.40; P<0.00001; I2=91%). Additionally, omarigliptin outperformed placebo in lowering fasting plasma glucose, 2-hour postprandial glucose, and in the percentage of participants achieving HbA1c levels below 7.0% and 6.5%. The glycemic efficacy of omarigliptin was similar to that of the ACG across all measures. Although the omarigliptin group experienced a higher incidence of hypoglycemic events compared to the PCG, the overall AEs, serious AEs, hypoglycemia, and severe hypoglycemia were comparable between the omarigliptin and control groups (PCG and ACG). Omarigliptin has a favorable glycemic efficacy and safety profile for managing T2DM.

Comparison of the efficacy of fish oil and probiotic supplementation on glucose and lipid metabolism in patients with type 2 diabetes: a systematic review and network meta-analysis.

Abnormalities in glucose and lipid metabolism contribute to the progression and exacerbation of type 2 diabetes mellitus (T2DM). Fish oil and probiotics are dietary supplements that have the potential to improve glucose and lipid metabolism. However, their efficacy remains unclear in T2DM patients. PubMed, Embase, and the Cochrane Library were retrieved to collect randomized controlled trials (RCTs) on the efficacy of fish oil or probiotic supplementation in T2DM patients from the database inception to December 13, 2023. Primary outcome indicators encompassed glycated hemoglobin (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR) and blood lipid profile (triglyceride (TG) and total cholesterol (TC). Secondary outcome indicators included inflammatory markers such as tumor necrosis factor -α (TNF-α) and adipocytokine (including leptin and adiponectin). The R software was used for statistical analysis, and GraphPad Prism was used for figure rendering. A total of 60 RCTs involving 3845 T2DM patients were included in the analysis. The results showed that the probiotics (Bifidobacterium, Lactobacillus, Lactococcus, Propionibacterium, etc.) were more effective in reducing HOMA-IR than fish oil (Surca = 0.935). Bifidobacterium demonstrated the highest efficacy in reducing HbA1c levels (Surca = 0.963). Regarding lipid metabolism, fish oil was superior to probiotics in lowering TG and TC levels (Surca values of 0.978 and 0.902, respectively). Furthermore, fish oil outperformed probiotics in reducing TNF-α (Surca = 0.839) and leptin (Surca = 0.712), and increasing adiponectin levels (Surca = 0.742). Node-splitting analysis showed good consistency (P > 0.05 for direct, indirect, and network comparison across various interventions). In T2DM patients, fish oil was more effective than probiotics in regulating lipid metabolism. Probiotics outperformed fish oil in regulating glucose metabolism particularly; specifically, Bifidobacterium showed higher efficacy in reducing blood glucose.

Impact of Non-Surgical Periodontal Therapy on HbA1c Levels of Type 2 Diabetes at Khyber College of Dentistry, Peshawar: A Quasi-Experimental Study

Background: Diabetes mellitus (DM) constitutes a spectrum of persistent metabolic disorders originating from irregular glucose metabolism due to insufficient insulin production, compromised insulin function, or a combination of the two, leading to elevated blood sugar levels. This study assessed the influence of non-surgical periodontal therapy on glycated hemoglobin (HbA1c) levels in individuals with Type 2 Diabetes. Methods: This quasi-experimental study was conducted at Khyber College of Dentistry, Peshawar, with 40 participants diagnosed with Type 2 diabetes for more than 3 years and suffering from chronic periodontitis. Patients with Type 1 diabetes, pregnant women, and those with other medical complications were excluded. HbA1c levels were assessed at baseline, and non-surgical periodontal therapy was administered. Patients were educated and scheduled for a follow-up after 3 months when HbA1c levels were reassessed. A paired t-test was employed to compare HbA1c levels pre-and post-intervention. Results: In this study, males were 29 (58%) whereas 21 (42%) females. The mean value of HbA1c was less post-treatment with non-surgical periodontal therapy (6.928±0.866%) than pretreatment (9.048±0.73%) and results were statistically significant (p&lt;0.001). After receiving therapy, the HbA1c level was significantly reduced in both genders (p&lt;0.001). Irrespective of smoking status, the reduction of HbA1c level was statistically significant (p=0.01). Conclusion: Non-surgical periodontal treatment significantly reduces HbA1c levels, indicating a potentially positive impact on glycemic control in individuals with diabetes, which has enhanced the dentist’s role as a part of the health team, and timely interventions can significantly improve prognosis.

Cardiovascular diseases consequences of type 1, type 2 diabetes mellitus and glycemic traits: A Mendelian randomization study

ObjectiveThis Mendelian randomization (MR) study aimed to investigate the relationships between type 1 diabetes (T1D), type 2 diabetes (T2D), and glycemic traits, including fasting insulin, fasting glucose, and HbA1c, with cardiovascular diseases (CVDs). MethodsWe selected genetic instruments for predisposition to T1D, T2D, fasting insulin, fasting glucose, and HbA1c based on published genome-wide association studies. Using a 2-Sample MR approach, we assessed associations with 12 common CVDs sourced from the FinnGen and UK Biobank studies, along with stroke subtypes obtained from the GIGASTROKE and MEGASTROKE Consortium. ResultsT1D was associated with SVS. T2D showed associations with AIS, LAA, CES, SVS, coronary heart disease, myocardial infarction, pulmonary embolism, DVT of lower extremities, peripheral vascular diseases. Genetically predicted higher HbA1c levels were associated with eight CVDs. The results of MVMR aligned with the primary findings for T1D and T2D. ConclusionsT1D and T2D exhibit different genetic predisposition to CVDs. BMI, LDL, and HDL play intermediary roles in connecting TID and T2D to specific types of CVDs, providing insights into the potential underlying pathways and mechanisms involved in these relationships. Strategies aimed at achieving sustained reductions in HbA1c levels may offer potential for reducing the risk of various CVDs.

Association Between the Magnitude of Glycemic Control and Body Weight Loss With GLP-1 Receptor Agonists and Risk of Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-analyses of Randomized Diabetes Cardiovascular Outcomes Trials.

Reduction of major atherosclerotic cardiovascular events (MACE) has not been consistent among different glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess the association between the magnitude of glycemic control, body weight loss, and reductions in systolic blood pressure (SBP)and low-density lipoprotein cholesterol (LDL-C) achieved through GLP-1 RA therapy and MACE. Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through March 2023. Studies were eligible if they were cardiovascular outcome trials (CVOTs) comparing GLP-1 RAs versus placebo in T2DM patients. The outcome of interest was 3-point MACE - cardiovascular death, myocardial infarction, or stroke. Random-effects meta-regression analyses evaluated the associations between reductions of HbA1c, body weight, SBP and LDL-C and reduction of MACE. Overall, 8 CVOTs were included (60079 patients, 30693 with GLP-1 RAs). Reductions of HbA1C were associated with the reduction of 3P-MACE (Log RR -0.290 [95% CI -0.515;-0.064], p = 0.012), with an estimated RR reduction of 25% for each 1% absolute reduction in HbA1C levels. Body weight loss was associated with the reduction of 3P-MACE (Log RR -0.068 [95% CI -0.135;-0.001], p = 0.047), with an estimated RR reduction of 7% for each 1kg reduction in body weight. Reductions of SBP (Log RR -0.058 [95% CI -0.192;0.076], p = 0.396) and LDL-C (Log RR -0.602 [95% CI -4.157;2.953], p = 0.740) were not associated with the reduction of 3P-MACE. In T2DM patients, more potent GLP-1 RAs in reducing HbA1c and body weight were associated with greater reductions of MACE.

Effectiveness of insulin degludec/liraglutide versus insulin degludec/insulin aspart in Japanese patients with type 2 diabetes.

To evaluate and compare the effectiveness of once-daily insulin degludec/liraglutide (IDegLira) to that of once-daily insulin degludec/insulin aspart (IDegAsp) after switching from basal insulin therapy at 6months by assessing changes in hemoglobin A1c (HbA1c), body weight, and insulin doses in patients with type 2 diabetes (T2D). A total of 91 patients with T2D with HbA1c levels exceeding 7.0% were included in this study. Adjusted least square mean changes in HbA1c, body weight, and total insulin doses were compared between the IDegLira group and IDegAsp group. Subgroup analyses were performed, stratified by median values of HbA1c (< 8.5 and ≥ 8.5%), obesity (body mass index < 25 and ≥ 25kg/m2), and basal insulin doses (< 14 and ≥ 14 units) at baseline to assess treatment interaction by subgroup. The IDegLira group showed a greater reduction in HbA1c levels than the IDegAsp group (-0.17 vs -0.79%, p = 0.003) with comparable body weight changes. The analyses of adjusted mean changes of total insulin doses showed that the IDegAsp group had a larger increase than the IDegLira group (3.64 vs 1.30 unis, p = 0.016). The effect of IDegLira on HbA1c levels was superior to that of IDegAsp in patients with high HbA1c. There were no inter-group differences in the rate of hypoglycemic episodes. Once-daily IDegLira had greater effects on HbA1c and a lesser increase in insulin doses than IDegAsp when patients are switched from basal insulin therapy. Moreover, the effect on HbA1c was enhanced in patients with high HbA1c levels at baseline.

Glycemic Control, Weight Management, Cardiovascular Safety, and Cost-Effectiveness of Semaglutide for Patients with Type 2 Diabetes Mellitus: A Rapid Review and Meta-analysis of Real-World Studies.

Semaglutide is a high-profile glucose-lowering drug that medical decision-makers have acknowledged in recent years. This rapid review aims to provide evidence-based clinical recommendations for the treatment of type 2 diabetes mellitus (T2DM) with semaglutide. We conducted a rapid review of randomized controlled trial (RCT)-based meta-analyses (MAs) and systematic reviews (SRs) of cost-effectiveness analyses (CEAs) compared to other glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or placebo in patients with T2DM. Prospective cohort real-world studies (RWS) were also retrieved and subjected to MA. Four databases, including PubMed, the Cochrane Library, Embase, and ISPOR, were searched from inception to 5 March 2023. The outcomes of interest were hemoglobin A1c (HbA1c), body weight, major adverse cardiovascular events (MACE), and economic outcomes such as quality-adjusted life-years and total cost. We identified 33 publications: 22 RCT-based MAs, 1 SR of CEAs, and 10 RWS. Evidence showed that semaglutide at usual doses was associated with superior reductions in HbA1c and weight compared to most GLP-1 RAs in patients with T2DM who were drug naive, receiving basal insulin, or using oral hypoglycemic agents, and it was also associated with a lower number of MACE and was more cost-effective. Further, once-weekly semaglutide resulted in a significant reduction in HbA1c levels (-1.1%) and body weight (-4.88kg) in routine clinical practice. This review consolidates the positive current evidence base for prescribing semaglutide to patients with T2DM, but further rigorous studies are still urgently required to develop practice guidelines as innovative drugs become commercially available.

Sodium-glucose cotransporter-2 inhibitors (SGLT2) in frail or older people with type 2 diabetes and heart failure: a systematic review and meta-analysis.

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. We included data from 20 studies (22 reports; N = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference -0.13, 95%CI: -0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: -0.69 to 0.95), cardiac death (RR 0.80, 95%CI: -0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59-0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase.

Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology

The limited understanding of the heterogeneity in the treatment response to antidiabetic drugs contributes to metabolic deterioration and cardiovascular complications1,2, stressing the need for more personalized treatment1. Although recent attempts have been made to classify diabetes into subgroups, the utility of such stratification in predicting treatment response is unknown3. We enrolled participants with type 2 diabetes (n = 239, 74 women and 165 men) and features of severe insulin-deficient diabetes (SIDD) or severe insulin-resistant diabetes (SIRD). Participants were randomly assigned to treatment with the glucagon-like peptide 1 receptor agonist semaglutide or the sodium–glucose cotransporter 2 inhibitor dapagliflozin for 6 months (open label). The primary endpoint was the change in glycated haemoglobin (HbA1c). Semaglutide induced a larger reduction in HbA1c levels than dapagliflozin (mean difference, 8.2 mmol mol−1; 95% confidence interval, −10.0 to −6.3 mmol mol−1), with a pronounced effect in those with SIDD. No difference in adverse events was observed between participants with SIDD and those with SIRD. Analysis of secondary endpoints showed greater reductions in fasting and postprandial glucose concentrations in response to semaglutide in participants with SIDD than in those with SIRD and a more pronounced effect on postprandial glucose by dapagliflozin in participants with SIDD than in those with SIRD. However, no significant interaction was found between drug assignment and the SIDD or SIRD subgroup. In contrast, continuous measures of body mass index, blood pressure, insulin secretion and insulin resistance were useful in identifying those likely to have the largest improvements in glycaemic control and cardiovascular risk factors by adding semaglutide or dapagliflozin. Thus, systematic evaluation of continuous pathophysiological variables can guide the prediction of the treatment response to these drugs and provide more information than stratified subgroups (NCT04451837).

Effect of Isometric and Dynamic Resistance Exercises on Functional Performance and Glycoprotein-bound Haemoglobin of Type 2 Diabetes Mellitus Patients with Knee Osteoarthritis: An Interventional Study

Introduction: Osteoarthritis (OA) is the most prevalent articular and rheumatologic condition, impacting over 80% of individuals aged 55 and above. There exists a significant correlation between Type 2 Diabetes Mellitus (T2DM) and OA. Both Diabetes Mellitus (DM) and OA are common afflictions. Physiotherapy plays a crucial role in alleviating pain and mitigating issues linked to the early stages of knee OA and DM. The rationale of this study is to determine whether isometric resistance exercise can achieve comparable or superior outcomes to dynamic resistance exercise in terms of long-term glycaemic control and physical function, while also being more tolerable for individuals with knee OA. Aim: To compare the efficacy of resistance exercises in diabetic patients with knee OA and specifically to examine how two resistance exercise protocols influence glycated haemoglobin (HbA1c) levels and functional performance. Materials and Methods: An interventional study was conducted using a convenience sampling technique. Approximately, 30 subjects were selected from the primary physiotherapy outpatient department in Chennai, Tamil Nadu, India. The study lasted for 12 weeks, from July 2022 to September 2022. The total population was split into two groups: Group-A received dynamic resistance exercises, whereas Group-B underwent isometric resistance exercises. Both pre- and post-treatment evaluations were performed using the Western Ontario and McMaster Universities OA Index questionnaire (WOMAC), alongside measuring HbA1c levels in all participants. Care instructions emphasised weight reduction, maintaining a balanced diet, and avoiding prolonged periods of standing. Paired t test was used to compare the pre and post test WOMAC scores and p&lt;0.05 was considered statistically significant. Results: Significant changes were observed in WOMAC scores and HbA1c pre-post comparison. The study revealed a statistically significant difference in reducing pain, enhancing functional performance, and lowering HbA1c levels among both groups (p≤0.001). Conclusion: The results indicate that both groups experienced effective pain relief and reduced HbA1c levels after the treatment period. However, subjects treated with dynamic resistance exercises demonstrated greater enhancements in functional performance and reductions in HbA1c levels compared to the isometric resistance exercises.

A Transtheoretical Model-Based Online Intervention to Improve Medication Adherence for Chinese Adults Newly Diagnosed With Type 2 Diabetes: A Mixed-Method Study.

Type 2 diabetes mellitus (T2DM) is increasing in China, with medication non-adherence being a significant contributor to uncontrolled T2DM. The Transtheoretical Model (TTM) has shown effectiveness in chronic disease management, but few studies have applied it in online interventions for T2DM medication adherence. The study aimed to develop and investigate the effects of a TTM-based online health education program on promoting positive stage of change (SOC) movement, improving self-efficacy and medication adherence, as well as reducing HbA1c levels in newly diagnosed patients with T2DM. This sequential mixed-method study was conducted from April 2023 to March 2024. Using the TTM framework, the study initially explored 32 participants' experiences with hypoglycemic medications, health information acquisition, and perspectives on online programs. Then, a quasi-experimental study design was conducted. Two communities were randomly assigned as the intervention (n = 91) and comparison (n = 98) groups, with 189 newly diagnosed middle-aged T2DM patients from various SOC. The intervention group received short videos health education and participated in WeChat group discussions, compared with usual care in the comparison group. Data were collected at baseline, 3-month, and 6-month follow-ups. The intervention group was more likely to achieve positive SOC movement (P < .001, Adj OR = 13.69 95% CI = 6.76-27.71) compared to the comparison group. The intervention group also had significantly higher mean CDMSS-11 and MMAS-8 scores at 6 months (P = .03 and <.001, respectively) and more likely to achieve clinically significant glycated Hemoglobin (HbA1c) change at 3 months (P < .001, Adj OR = 3.91, 95% CI = 1.77-8.63) and at 6 months (P < .001, Adj OR = 5.62, 95% CI = 2.70-11.69) compared to the comparison group. These findings support that applying the TTM to develop an online program could promote behavior change, improve self-efficacy and medication adherence, and could lead to better glycemic control in newly diagnosed T2DM patients.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Elevated HbA1c Level has a Linear Association with Infertility in Women.

Hemoglobin A1c (HbA1c) is commonly known as a plasma glucose monitoring indicator. However, the relationship between HbA1c and fertility has not been clarified in previous literature. This study aims to investigate the association between HbA1c and the incidence of infertility. Data from the U.S. National Health and Nutrition Examination Survey (NHANES) 2013 - 2018 was utilized. The final study contained 3,319 women aged 18 to 45 years. Multivariable logistic regression models were performed to analyze the correlation of HbA1c on female infertility with adjustment for relevant covariates including demographic characteristics, lifestyle, clinical laboratory biomarkers, and comorbidities. We found a significant linear correlation between HbA1c and infertility even in the fully-adjusted model (OR: 1.27, 95% CI: 1.07 - 1.5). Subgroup analysis stratified by age showed a significant linear association with HbA1c and infertility in the younger group (age < 35 years). Whereas, results showed a lack of significant association in the older group (age > 35 years). Data from a population-based sample in US women aged 18 to 45 years suggest that elevated HbA1c level correlated with increasing risk of infertility, even HbA1c is within the normal range. Further well-designed randomized controlled trials are needed to determine whether strategies to reduce HbA1c levels are effective in decreasing the incidence of female infertility.

Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review.

Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.

Efficacy and Safety of Continuous Glucose Monitoring and Intermittently Scanned Continuous Glucose Monitoring in Patients With Type 2 Diabetes: A Systematic Review and Meta-analysis of Interventional Evidence.

Traditional diabetes self-monitoring of blood glucose (SMBG) involves inconvenient finger pricks. Continuous glucose monitoring (CGM) and intermittently scanned CGM (isCGM) systems offer CGM, enhancing type 2 diabetes (T2D) management with convenient, comprehensive data. To assess the benefits and potential harms of CGM and isCGM compared with usual care or SMBG in individuals with T2D. We conducted a comprehensive search of MEDLINE, Embase, the Cochrane Library, Web of Science, and bibliographies up to August 2023. We analyzed studies meeting these criteria: randomized controlled trials (RCT) with comparison of at least two interventions for ≥8 weeks in T2D patients, including CGM in real-time/retrospective mode, short-/long-term CGM, isCGM, and SMBG, reporting glycemic and relevant data. We used a standardized data collection form, extracting details including author, year, study design, baseline characteristics, intervention, and outcomes. We included 26 RCTs (17 CGM and 9 isCGM) involving 2,783 patients with T2D (CGM 632 vs. usual care/SMBG 514 and isCGM 871 vs. usual care/SMBG 766). CGM reduced HbA1c (mean difference -0.19% [95% CI -0.34, -0.04]) and glycemic medication effect score (-0.67 [-1.20 to -0.13]), reduced user satisfaction (-0.54 [-0.98, -0.11]), and increased the risk of adverse events (relative risk [RR] 1.22 [95% CI 1.01, 1.47]). isCGM reduced HbA1c by -0.31% (-0.46, -0.17), increased user satisfaction (0.44 [0.29, 0.59]), improved CGM metrics, and increased the risk of adverse events (RR 1.30 [0.05, 1.62]). Neither CGM nor isCGM had a significant impact on body composition, blood pressure, or lipid levels. Limitations include small samples, single-study outcomes, population variations, and uncertainty for younger adults. Additionally, inclusion of <10 studies for most end points restricted comprehensive analysis, and technological advancements over time need to be considered. Both CGM and isCGM demonstrated a reduction in HbA1c levels in individuals with T2D, and unlike CGM, isCGM use was associated with improved user satisfaction. The impact of these devices on body composition, blood pressure, and lipid levels remains unclear, while both CGM and isCGM use were associated with increased risk of adverse events.

Dose–response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial

Aims/hypothesisThe aim of this study was to assess the dose–response effects of the subcutaneous glucagon receptor/glucagon-like peptide-1 receptor dual agonist survodutide (BI 456906) on HbA1c levels and bodyweight reduction.MethodsThis Phase II, multicentre, randomised, double-blind, parallel-group, placebo-controlled study, conducted in clinical research centres, assessed survodutide in participants aged 18–75 years with type 2 diabetes, an HbA1c level of 53–86 mmol/mol (7.0–10.0%) and a BMI of 25–50 kg/m2 on a background of metformin therapy. Participants were randomised via interactive response technology to receive survodutide (up to 0.3, 0.9, 1.8 or 2.7 mg once weekly [qw; dose group (DG) 1–4, respectively] or 1.2 or 1.8 mg twice weekly [DG 5 and 6, respectively]), placebo or semaglutide (up to 1.0 mg qw). Participants and all those involved in the trial conduct/analysis were blinded; the semaglutide arm was open-label. The primary endpoint was absolute change from baseline in HbA1c after 16 weeks’ treatment. The key secondary endpoint was relative change from baseline in bodyweight after 16 weeks’ treatment.ResultsA total of 413 participants were randomised (DG1, n=50; DG2, n=50; DG3, n=52; DG4, n=50; DG5, n=51; DG6, n=50; semaglutide, n=50; placebo, n=60). The full analysis set comprised 411 treated participants (DG6, n=49; placebo, n=59). Adjusted mean (95% CI) HbA1c decreased from baseline (mean ± SD 64.7±9.2 mmol/mol [8.07±0.84%] after 16 weeks’ treatment: DG1 (n=41), −9.92 mmol/mol (−12.27, −7.56; −0.91% [−1.12, −0.69]); DG2 (n=46), −15.95 mmol/mol (−18.27, −13.63; −1.46% [−1.67, −1.25]); DG3 (n=36), −18.72 mmol/mol (−21.15, −16.29; −1.71% [−1.94, −1.49]); DG4 (n=33), −17.01 mmol/mol (−19.59, −14.43; −1.56% [−1.79, −1.32]); DG5 (n=44), −17.84 mmol/mol (−20.18, −15.51; −1.63% [−1.85, −1.42]); DG6 (n=36), −18.38 mmol/mol (−20.90, −15.87; −1.68% [−1.91, −1.45]). The mean reduction in HbA1c was similar with low-dose survodutide (DG2: −15.95 mmol/mol [−1.46%]; n=46) and semaglutide (−16.07 mmol/mol [−1.47%]; n=45). Mean (95% CI) bodyweight decreased dose-dependently up to −8.7% (−10.1, −7.3; DG6, n=37); survodutide ≥1.8 mg qw produced greater bodyweight reductions than semaglutide (−5.3% [−6.6, −4.1]; n=45). Adverse events (AEs) were reported for 77.8% of survodutide-treated participants (mainly gastrointestinal), 52.5% receiving placebo and 52.0% receiving semaglutide.Conclusions/interpretationSurvodutide reduced HbA1c levels and bodyweight after 16 weeks’ treatment in participants with type 2 diabetes. Dose-related gastrointestinal AEs could be mitigated with slower dose escalations.Trial registrationClinicalTrials.gov NCT04153929 and EudraCT 2019-002390-60.FundingBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.Graphical

Effectiveness of Continuous Glucose Monitoring on Metrics of Glycemic Control in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

To provide a systematic review and meta-analysis synthesizing the findings of randomized controlled trials (RCTs) of continuous glucose monitors (CGMs) in the management of adults with type 2 diabetes mellitus (T2DM) on glucose control and clinical outcomes. MEDLINE, Embase, and Cochrane were searched for RCTs that assessed the effectiveness of real-time CGM (rt-CGM) or flash CGM (FGM) in adults (≥18 years) with T2DM that reported on at least 1 of the following outcomes: hemoglobin A1c (HbA1c), time in range, time in hyperglycemia, or time in hypoglycemia. The GRADE approach was used to assess certainty of evidence for primary outcomes. Fourteen RCTs assessing CGM were included, with 825 patients in 9 RCTs using rt-CGM and 822 in 5 RCTs using FGM. Moderate certainty of evidence indicated that use of CGM had a modest but statistically significant reduction in HbA1c levels of about 0.32%. Our analyses of each device type separately showed similar reductions in HbA1c (0.34% and 0.33%, respectively, for rt-CGM and FGM), with trends for improvement in other glucose metrics favoring rt-CGM over self-monitored blood glucose. Both rt-CGM and flash CGM led to modest but statistically significant declines in HbA1c among individuals with T2DM, with little heterogeneity in the results. However, the duration of the included RCTs was relatively short and few studies reported on important clinical outcomes, such as adverse events, emergency department use, or hospitalization. Longer term studies are needed to determine if the short-term improvements in glucose control leads to improvements in clinically important outcomes.

Association between intensity of glycemic control with GLP-1 receptor agonists and risk of atherosclerotic cardiovascular disease: a systematic review and meta-regression

Abstract Background Several glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown to reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (DM). However, this reduction has not been consistent among different GLP-1 RAs. We conducted a systematic review and meta-regression analyses to evaluate the association between the intensity of glycemic control achieved byGLP-1 RAs therapy in patients with type 2 DM and the reduction of MACE as well as to identify potential mechanisms involved. Methods Electronic databases (MEDLINE, CENTRAL, SCOPUS) were searched through November 2022. Studies were considered eligible if they were cardiovascular outcomes randomized trials (CVOTs) comparing GLP-1 RAs versus placebo in type 2 DM patients. Trials including non-diabetic patients and GLP-1 RAs refused by European Medicines Agency or US Food and Drug Administration were excluded. The outcome of interest was 3-point MACE (CV death, MI, or stroke). Random-effects meta-analyses and meta-regression evaluated associations between glycemic control withGLP-1 RAs and study outcomes. Secondary meta-regression analyses were performed for body weight and blood pressure (BP) variation. Results Overall, 8 CVOTs were included, with a total of 60080 patients (30694 treated withGLP-1 RAs). GLP-1 RAs were associated with a lower incidence of 3P-MACE (RR 0.876; 95% CI 0.821-0.935, p&amp;lt;0.001). Mean HbA1C reduction was 0.57% in patients treated withGLP-1 RAs vs. placebo. Meta-regression showed that higher reductions of HbA1C levels were associated with lower risk of 3P-MACE (Log RR -0.286 [95% CI-0.512; -0.056], p=0.015), which translates into an estimated relative risk reduction of 25% for each 1% reduction in HbA1C (Figure 1A). There was a non-significant association between glycemic control and each of the 3P-MACE outcomes analysed separately. Body weight reduction was also associated with a lower risk of 3P-MACE (Log RR -0.067 [95% CI-0.134; 0.001], p=0.053), despite not meeting statistical significance (Figure 1B). Systolic BP decrease was not associated with reduced risk of 3P-MACE. Conclusions The better the glycemic control withGLP-1 RAs in type 2 DM patients, the greater the reduction in 3P-MACE. Body weight reduction may also play a potential role.Figure 1

Abstract 13815: Therapeutic Effects of Empagliflozin in Diabetic Patients After Acute Myocardial Infarction: Systematic Review and Meta-Analysis With Trial Sequential Analysis

Introduction: Empagliflozin is a new sodium-glucose transporter protein 2 (SGLT2) inhibitor. In addition to its anti-hyperglycemic effect, recent studies suggested that it may improve cardiac outcomes in diabetic patients with acute myocardial infarction. This systematic review and meta-analysis aims to test this hypothesis. Methods: We comprehensively searched PubMed, Scopus, Cochrane, and Web of Science. We included studies comparing empagliflozin versus placebo in diabetic patients with acute myocardial infarction. Our outcomes were the changes in plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), left ventricular ejection fraction% (LVEF%), and hemoglobin A1c (HbA1c) levels. We performed Trial Sequential Analysis (TSA), and we used mean difference (MD) and 95% confidence interval (CI) as our effect size with a random effects model. Results: Five studies (one cohort study and four randomized controlled trials), compromising 751 patients, were included. Empagliflozin significantly increased LVEF compared to placebo (MD = 1.80, 95% CI [0.50, 3.10], P =0.007), however, the TSA curve did not cross the conventional boundary for statistical significance, indicating that the available evidence did not reach the predetermined threshold. On the other hand, we observed no significant difference between the two groups in terms of NT-pro-BNP and HbA1c (MD = -136.59, 95% CI [-293.43, 20.25], P =0.09; MD= -0.72, 95% CI [-1.73, 0.29], P =0.16, respectively). Conclusions: Our meta-analysis reveals that among diabetic patients with acute myocardial infarction, empagliflozin failed to improve cardiac parameters such as LVEF and NT-pro-BNP without providing additional benefits in reducing HbA1c levels. Therefore further large-scale RCTs are warranted to ascertain our findings.