Type 2 diabetes (T2D) is a known risk factor for cardiovascular (CV) disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, improve glycemic control and are associated with weight loss, but the impact of weight loss on major adverse cardiovascular events (MACE) when taking semaglutide is not fully understood. This post hoc analysis of the SUSTAIN-6 trial aimed to examine the correlation between weight loss with semaglutide and the occurrence of MACE (nonfatal myocardial infarction, nonfatal ischemic stroke, and CV death). This study is a single-arm, post hoc, observational analysis of the randomized, double-blind, placebo-controlled SUSTAIN-6 cardiovascular outcomes trial (NCT01720446). Participants in the semaglutide group (N = 1479) were stratified into four weight loss categories on the basis of the percentage change in body weight from baseline to 56weeks: no loss/gain, < 5% loss, 5-10% loss, and > 10% loss. The occurrence of MACE during the follow-up period (weeks 56-104) was compared across weight loss categories using descriptive statistics and logistic regression adjusted for age and sex. Categorical variables were compared across groups using chi-squared tests, and continuous variables were compared using analysis of variance (ANOVA). Point estimates of MACE incidence did not differ by weight loss category (P = 0.73). The MACE event rate was comparable across weight loss categories (no loss/gain: 1.05%; < 5% loss: 1.69%; loss 5-10%: 1.06%, > 10% loss: 0.89%). Compared with the no weight loss/gain category, no degree of weight loss was associated with lower adjusted odds (odds ratio) of MACE (loss < 5%: 1.68; P = 0.66; loss 5-10%: 1.13; P = 0.77; loss > 10%: 1.06; P = 0.95). This post hoc analysis of SUSTAIN-6 did not find an association between the magnitude of weight loss achieved after 56weeks of semaglutide treatment and subsequent MACE risk in people with T2D, suggesting that weight-independent mechanisms may mediate the cardioprotective effects of semaglutide.

Diabetes mellitus presents a growing public health challenge across geographies including Asia, particularly in countries where blood glucose monitoring (BGM)-referring to capillary finger-prick self-monitoring of blood glucose (SMBG) using a meter and test strips-is underutilized. Having evolved and improved over recent decades, glucose monitoring (GM)-including SMBG and continuous glucose monitoring (CGM)-has become an essential tool for effective diabetes management, yet remains underutilized because of systemic, economic, and educational barriers. This work synthesizes expert insights and published evidence to develop best practice recommendations for BGM. A targeted literature review (TLR) was conducted across five thematic domains: monitoring practices, clinical decision-making, patient engagement and adherence, technology and innovation, and policy and reimbursement. Insights were complemented by a structured expert forum involving clinicians from seven Asian countries, underscoring larger implications in geographies where SMBG remains underutilized within the diabetes care continuum. The forum highlighted disparities in device access, affordability, and insurance coverage, and emphasized the need for structured diabetes self-management education (DSME) and digital integration. Findings support the use of structured SMBG for non-insulin-treated type2 diabetes and CGM for insulin-treated individuals and those at risk of hypoglycemia. Evidence from the literature review also highlighted the importance of proper SMBG technique, with common errors such as inadequate handwashing, repeated lancet use, and excessive finger squeezing contributing to inaccurate readings and finger-site injuries. Hybrid models combining CGM and SMBG for calibration or confirmation are pragmatic solutions balancing clinical utility and affordability. Digital platforms, AI-driven analytics, and mobile apps enhance patient engagement and glycemic control but face challenges of scalability and regulation. Policy reforms, including inclusion of BGM in national health benefit packages, expanded insurance coverage, and public-private partnerships, are critical to improving access. The recommendations advocate for personalized, context-specific monitoring strategies that balance clinical efficacy with affordability and infrastructure realities. This consensus-based framework aims to guide healthcare professionals in optimizing BGM practices and improving long-term outcomes for people living with diabetes. FITTER BiG is a new extension of the long-standing FITTER initiative, which has provided insulin injection technique recommendations for more than two decades. FITTER BiG complements this work by focusing specifically on best practice recommendations for blood glucose monitoring. FITTER BiG will provide BGM-specific recommendations designed to complement the injection technique guidance outlined in the FITTER Forward consensus statement (Klonoff et al. Mayo Clin Proc 100:682-699, 2025 [1]).

Real-world data on escalation of once-weekly semaglutide from 0.5 to 1.0mg remain limited. Therefore, we aimed to evaluate the effectiveness and safety of this dose escalation in routine clinical practice. This was a single-center, retrospective cohort study involving adults with type 2 diabetes who received an escalated once-weekly semaglutide dose from 0.5 to 1.0mg in routine clinical care. The primary outcome was within-patient change in glycated hemoglobin (HbA1c) level 24weeks after the initial prescription of 1-mg semaglutide. Secondary outcomes included changes in metabolic parameters and the incidence of newly documented adverse events after escalation to 1.0mg. Efficacy was analyzed in a prespecified on-treatment set, and safety was assessed in an all-exposed set. In the efficacy set (n = 126), the HbA1c level decreased by 0.40% ± 0.70% and body weight by 2.2 ± 2.7kg at week 24 (both p < 0.01). Additionally, reductions were observed in alanine aminotransferase and γ-glutamyl transpeptidase levels, total number of concomitant glucose-lowering agents, and total daily insulin dose. In the safety set (n = 128), gastrointestinal adverse events were the most frequent (20.3%), particularly nausea (14.1%). Dose reduction was required in 12.5% of patients, mostly owing to gastrointestinal symptoms, and discontinuation for any reason occurred in 5.5%; only one patient (0.8%) discontinued treatment because of an adverse event. No serious drug-related adverse events were recorded. In this real-world cohort, escalation of once-weekly semaglutide dose to 1.0mg was associated with additional reductions in HbA1c level and body weight, without serious adverse events. Although causal incremental benefit cannot be established because of the single-arm design without a 0.5-mg maintenance comparator, these findings may support clinical decision-making regarding dose intensification in patients experiencing suboptimal control with 0.5-mg semaglutide. UMIN Clinical Trials Registry (UMIN-CTR), UMIN000059813, retrospectively registered on November 18, 2025.

This study aimed to examine psychosocial well-being, quality of life (QoL), and productivity in people with type 1 diabetes (pwT1D) who were experiencing recurrent severe hypoglycemic events (SHEs) and impaired awareness of hypoglycemia (IAH), despite using continuous glucose monitors (CGMs). The study utilized a cross-sectional, observational design which incorporated an online survey about SHE experiences, diabetes-related complications, psychosocial burden, QoL, and productivity in a sample of adult pwT1D who use CGM in the United States. Participants completed measures of IAH status (modified Gold score ≥ 4 = IAH), diabetes distress (DDS-17), fear of hypoglycemia (HFS-II), QoL (DIDP and EQ-5D-5L), and productivity (DPM). Participants were categorized into two cohorts based on self-reported history of SHEs and IAH: the cohort of recurrent SHE [≥ 2 SHEs in the past 12months] with IAH, and the cohort of No SHE and No IAH to provide context. Unadjusted comparisons (Welch's ttest, Pearson's chi-squared test) were conducted to describe differences across cohorts. In this US study population of adult CGM users, the recurrent SHE (≥ 2) with IAH cohort included 174 participants, and the No SHE and No IAH cohort included 689 participants. On average, participants with recurrent SHEs and IAH reported 8.6 SHEs in the past year. Compared to those with No SHE and No IAH, those with recurrent SHEs and IAH had a higher psychosocial burden (fear of hypoglycemia and diabetes distress), lower QoL, worse overall health status, and reduced productivity (all p < 0.001). Despite using CGM, adults with T1D with recurrent SHEs and IAH experienced lower psychosocial well-being, QoL, and reduced productivity compared to adults with T1D with no SHEs and no IAH, highlighting the unmet need for novel therapies for this group.

Tirzepatide has been associated with significant reductions in body weight in randomized clinical trials. However, real-world evidence evaluating the multisystemic effects of tirzepatide across the cardio-metabolic-kidney (CKM) continuum remains limited. The aim of this study was to assess the real-world persistence-driven cumulative benefits of tirzepatide beyond weight reduction in adults with obesity but without type 2 diabetes mellitus (T2DM). This single-center observational cohort study evaluated in the United Arab Emirates adults with obesity (body mass index [BMI] ≥ 30kg/m2) treated with tirzepatide. Participants were stratified by treatment persistence: ≤ 1year (short-term) and > 1year (long-term). Anthropometric, glycemic, lipid, hepatic, and renal outcomes were assessed at baseline and follow-up. One hundred participants (25 women; mean age 37.6 ± 10.0years; baseline BMI35.0[33.0-39.0]kg/m2) were included. Median weight reduction was - 8.1% in the short-term group and - 22.6% in the long-term group (p < 0.001). 62% of long-term treated individuals achieved > 15% weight loss versus 20% among short-term users. Significant between-group differences were observed in BMI (- 8.3% vs. - 19.1%), waist circumference (- 4.0% vs. - 9.2%), and glycated hemoglobin (HbA1c) (- 5.0% vs. - 7.2%). Total cholesterol decreased by - 10.1% vs. - 18.7% (p = 0.005), low-density lipoprotein cholesterol (LDL-C) by - 9.6% vs. - 30.5% (p < 0.001), and triglycerides by - 11.2% vs. - 32.5% (p < 0.001). Liver enzymes, aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) declined by - 11.3% and - 13.2%, respectively, in long term group with no significant improvement in short term group (between-groups p values for both liver enzymes < 0.05). Serum creatinine declined significantly in the long-term group (- 6.6%, p < 0.001), estimated glomerular filtration rate (eGFR) increasing by + 3.2% (p = 0.001), and blood urea nitrogen (BUN) decreasing by - 7.8% (p = 0.006) while microalbuminuria showed no meaningful changes. Weight loss correlated with improvements in LDL-C, triglycerides, and SGOT, and inversely with high-density lipoprotein cholesterol (HDL-C) changes. Tirzepatide showed greater cumulative benefits across CKM syndrome outcomes during the second treatment year, highlighting the need to overcome adherence barriers in real-world settings.

In this new era, heart transplantation (HT) is rapidly gaining popularity worldwide. Patients with end-stage heart disease are often candidates for HT. However, studies have shown that more than 30% of patients who undergo HT have pre-existing diabetes mellitus (DM), which is associated with a higher risk of graft failure and death. In this analysis, we aimed to assess the impact of sodium-glucose co-transporter 2 (SGLT2) inhibitors on clinical outcomes in patients with DM following HT. Online databases were searched for relevant publications. The statistical analysis was performed using the RevMan software version 5.4. The clinical outcomes included rejection post-HT, mortality, sepsis, weight reduction, change in body mass index (BMI), change in serum creatinine level, glomerular filtration rate (eGFR), and improvement in glycated hemoglobin (HbA1c). For dichotomous data, risk ratios (RR) with 95% confidence intervals (CI) were used to summarize the analysis. However, for continuous data, weight mean difference (WMD) with 95% CI was used. Eight studies with a total number of 2755 participants were included in this analysis. Our current results showed that rejection risk post HT was significantly lower in the SGLT2 inhibitor group (RR: 0.85, 95% CI: 0.78-0.93; P = 0.0001). The mortality risk was not significantly different (RR: 0.64, 95% CI: 0.32-1.29; P = 0.21). Similarly, sepsis following HT was similar in both groups (RR: 1.62, 95% CI: 0.13-20.11; P = 0.71). No significant differences were observed in weight reduction, BMI, change in serum creatinine level, change in eGFR, or improvement in HbA1c following HT. In participants with DM following HT, SGLT2 inhibitors significantly reduced rejection post transplantation. However, its impact on other important clinical outcomes, including mortality, should be further assessed with more data in future studies.

Glucagon-like peptide1 receptor agonists (GLP-1RAs) are key therapies for type2 diabetes and obesity, regulating blood glucose by mimicking endogenous GLP-1. Despite efficacy, GLP-1RAs are associated with adverse reactions across multiple organ systems. To address the gap in class-wide comparative safety analyses beyond previous studies limited to single drugs or organ systems, this study systematically evaluated adverse events for all approved GLP-1RAs to identify hidden risks and support clinical decision-making. We conducted a disproportionality analysis using the World Health Organization pharmacovigilance database (VigiBase) data up to January 2025. Reporting odds ratio (ROR) and information component (IC) were calculated for seven GLP-1RAs. Signals were considered significant when ROR025 > 1 and IC025 > 0. Subgroup analyses were stratified by gender and age. We aimed to synthesize and analyze existing randomized controlled trials (RCT) to validate VigiBase mining results. Among 348,649 reports, gastrointestinal disorders were the most frequent System Organ Class. Notable signals included tirzepatide with "abdominal pain" (ROR025 = 53.54), liraglutide with "drug ineffective" (ROR025 = 31.14) and "pancreatitis" (ROR025 = 4.24), exenatide with "injection site pain" (ROR025 = 70.14), and albiglutide with "device use error" (ROR025 = 1424.33). Male patients and younger adults (18-44years) generally showed higher positive reporting rates. This study provides a comprehensive safety comparison across all seven approved GLP-1RAs, confirming known risks and revealing drug-specific signals-such as injection-related issues and paradoxical hyperglycemia. These findings aid personalized treatment strategies and post-marketing surveillance.

The past year has continued the rapid evolution of diabetes technology across the monitoring, delivery, analytics, and patient-support domains. Improvements in continuous glucose monitoring (CGM) accuracy and wear-time options, widening use and regulatory expansion of automated insulin delivery (AID) systems, growth in connected insulin pens, maturation of digital therapeutics, and an influx of artificial intelligence (AI)-driven decision support tools have together shifted diabetes care toward tighter, more personalized, and more remote models of management. At the same time, device safety events, persistent affordability and access gaps, and data-interoperability and privacy challenges remind clinicians and policymakers that technology alone is not a panacea. This review summarizes the most important developments from last year (2025), highlights evidence from recent trials and regulatory actions, and discusses implications for practice and future directions.

Prediabetes is a frequently occurring condition with increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established antidiabetic agents, also used to treat obesity. There is limited, yet promising evidence on their use in prediabetes. T2DM was less frequent among subjects on liraglutide, semaglutide and tirzepatide compared with the control arm. Delayed progression to T2DM has also been observed. Furthermore, normoglycaemia was achieved for subjects on liraglutide (up to 66%), semaglutide (up to 81%) and tirzepatide (up to 93.3%). However, this effect was only partially sustained following drug withdrawal. GLP-1RAs have led to modest decreases in glycated haemoglobin (HbA1c), fasting glucose, weight and fat massloss, as well as increased insulin sensitivity and improved β-cell glucose-insulin dynamics. Decreased risk for atherosclerotic cardiovascular disease and heart failure was also demonstrated, mostly for subjects on tirzepatide. There is experimental evidence on improvements in liver dysfunction, pointing to potential benefits for metabolic dysfunction-associated steatotic liver disease (MASLD) in prediabetes. The safety profile was acceptable with mild-to-moderate gastrointestinal adverse effects being mostly reported. Future large randomised controlled trials are needed to ascertain the exact role of GLP-1RAs in prediabetes.

Type 2 diabetes mellitus (T2DM) prevalence in Iraq is projected to rise significantly by 2045, creating urgent need for optimized use of latest insulin therapies. An expert panel of eleven diabetes specialists convened to assess the evolving landscape of insulin therapies and explore how each option fits into current strategies to optimize T2DM management in Iraq. The panel reviewed international guidelines and local practice patterns through pre-meeting surveys. Discussions focused on initiation and intensification of insulin-based treatment in Iraq's context, considering accessibility challenges and patient characteristics. When hemoglobin A1c (HbA1c) is < 2% above target, basal insulin (BI) is recommended for patients with body mass index (BMI) ≤ 30. For BMI > 30, either GLP-1 receptor agonist (GLP-1 RA) monotherapy or a fixed ratio combination (FRC) of GLP-1 RA and BI is preferred. When HbA1c is ≥ 2% above target, initiation with BI and GLP-1 RA is advised across BMI groups. If glycemic targets are not achieved despite reaching 0.5 U/kg of BI, prandial insulin may be added via premixed regimen or basal-bolus regimens based on individual factors. Premix insulin remains an alternative when other options are unavailable. Key barriers in Iraq include high cost and limited availability of GLP-1 RAs, therapeutic inertia, and gaps in healthcare infrastructure. Final treatment decisions should consider disease severity, cardiovascular and renal comorbidities, and weight goals. The panel curated clinical practical recommendations about injectable insulin therapies and proposed a structured treatment algorithm tailored to Iraq's healthcare setting, prioritizing simplicity, efficacy, tolerability and accessibility. The panel emphasized the critical role of second-generation BIs and FRCs of BI and GLP-1 RA in Iraq's T2DM treatment algorithm, providing clear guidance on their optimal use and place in therapy, overcoming barriers, alongside enhanced education for healthcare providers and patients.