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Medical Journal
21st Nov, 2025
Diabetes Journals
OBJECTIVE In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use. RESEARCH DESIGN AND METHODS Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended. RESULTS Effects were analyzed by baseline MRA use ( n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse ( n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P -interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups ( P -interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI −41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo ( P -interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide ( P -interaction = 0.71). The safety profile of semaglutide was comparable between subgroups. CONCLUSIONS In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use.
OBJECTIVE To examine differences in case-fatality incidence among individuals with type 2 diabetes after major coronary or cerebrovascular events by geographic region and country income level. RESEARCH DESIGN AND METHODS We studied ADVANCE, TECOS, and EXSCEL participants who experienced within-trial major coronary (fatal or nonfatal myocardial infarction or sudden cardiac death) or cerebrovascular (fatal or nonfatal stroke) events. Case fatality was defined as death at the time or within 30 days of an event. We compared geographic regions with the reference category (Western Europe, North America, or Australia and New Zealand) and compared medium- and low-income countries, based on gross national income per capita by the World Bank, with the reference category (high). Unadjusted and adjusted analyses were performed for each trial using logistic regression for individual participant data, and the results were meta-analyzed. Adjustments were made for previous cardiovascular events and risk factors. RESULTS There were 2,574 major coronary and 1,247 cerebrovascular events among the 40,563 study participants. Postcoronary case-fatality adjusted odds ratios (95% CIs), compared with the reference group, were 3.31 (2.32–4.72), 2.78 (2.11–3.66), and 2.84 (1.71–4.73) for Asia, Central and Eastern Europe, and South America and Africa, respectively. The odds ratio for low- and middle-income versus high-income countries was 3.07 (2.41–3.92). Case fatality after a major cerebrovascular event did not differ by geographic region or income group. CONCLUSIONS Postcoronary case fatality was substantially higher in Asia, Central and Eastern Europe, and South America and Africa compared with Western countries and higher in low- and middle-income countries compared with high-income countries.
OBJECTIVE To determine the relationships between diabetes in pregnancy, birth weight, and stillbirth risk, using population-based data. RESEARCH DESIGN AND METHODS All singleton births in Victoria, Australia, between 2009 and 2020 were linked with perinatal and diabetes data. For each diabetes subgroup (type 1, type 2, and gestational diabetes [diet-controlled, insulin-controlled]), we assessed the proportion of infants with a birth weight in <10th or >97th centile, the probability of stillbirth by birth weight centile, and stillbirth rate per 1,000 pregnancies across gestational age. RESULTS Our study cohort of 860,042 included 100,856 pregnancies (11.7%) complicated by diabetes in pregnancy. Compared with no diabetes, women with diabetes in pregnancy gave birth earlier (median gestation 38.7 weeks vs. 39.4) and had more iatrogenic births (65% vs. 44%). Gestational diabetes was associated with a lower overall risk of stillbirth compared with no diabetes (diet-controlled: relative risk [RR] 0.75 [95% CI 0.64–0.89]; insulin-controlled: RR 0.37 [95% CI 0.25–0.50]). Compared with no diabetes, preexisting diabetes was associated with an increased risk of stillbirth (RR 2.68 [95% CI 2.01–3.56]), with this trend persisting across all gestational ages and birth weights. This was particularly observed among infants in the >97th centile (type 1 diabetes: RR 3.96 [95% CI 1.23–12.76]; type 2 diabetes: RR 4.02 [95% CI 1.71–9.47]). CONCLUSIONS In our cohort, gestational diabetes was associated with a lower stillbirth risk compared with no diabetes, which potentially can be explained by increased monitoring and earlier iatrogenic delivery. Preexisting diabetes was associated with a higher overall risk of stillbirth, with macrosomic fetuses in the >97th centile representing a particularly high-risk group requiring close monitoring.
OBJECTIVE New approaches to diabetes care are needed to better identify and manage diabetes emergencies outside of hospitals. RESEARCH DESIGN AND METHODS A descriptive analysis of routinely collected data was conducted using data from the Victorian Virtual Emergency Department (VVED) Diabetes, a telehealth service that provides emergency care, including ketone testing by ambulance personnel, for patients across Victoria, Australia, experiencing non–life-threatening diabetes-related emergencies. RESULTS Between July and December 2024, VVED Diabetes managed 868 diabetes-related emergencies, with 82.5% treated in the community, avoiding a physical emergency department visit. Referrals came from various sources, including Ambulance Victoria (26%), aged care facilities (29%), and self-registrations (20%). Hyperglycemia accounted for 46% of presentations. No clinical adverse events were reported, and patients gave positive feedback in a postdischarge survey. CONCLUSIONS VVED Diabetes delivers safe, timely, and high-quality treatment for individuals with diabetes who are acutely unwell, while ensuring the efficient use of limited hospital resources.
Continuous glucose monitoring (CGM) metrics, such as time in range (TIR), have become standard clinical tools for managing type 1 diabetes (T1D), offering substantial benefits in safety, convenience, and patient engagement. However, these metrics, while correlated with glycemic outcomes, are merely proxies for the true objective: minimizing the complications of dysglycemia.
OBJECTIVE This study aimed to evaluate the diabetic eye disease screening continuum at two academic centers and identify its barriers. RESEARCH DESIGN AND METHODS We analyzed health records from the University of California, San Francisco, and University of California, Irvine, to identify primary care patients needing diabetic eye screening. We tracked referrals, screenings, diagnoses, and treatments to evaluate predictors and the impact of an automated referral system. We analyzed physician notes using GPT-4o to determine reasons for missed screenings. RESULTS Of 8,240 unscreened patients with type 2 diabetes mellitus (T2DM), 43% received a referral, and only 16% completed screening within 1 year. Demographic, provider, and socioeconomic factors predicted adherence, with referrals being the strongest predictor. An automated referral system could improve screening rates to 22–34%. Clinician notes cited comorbidities, scheduling challenges, logistical issues, coronavirus disease 2019, and personal circumstances as barriers. CONCLUSIONS Many patients with T2DM remain unscreened after primary care visits. Although an automated referral system may partially improve adherence, additional tailored strategies are needed.
OBJECTIVE To identify prevalence, risk factors, and visual outcomes associated with occurrence and duration of lapses in proliferative diabetic retinopathy (PDR) care. RESEARCH DESIGN AND METHODS This was a retrospective national cohort study (2008–2023) of adults with PDR and ≥6 months of follow-up who were participating in the Sight Outcomes Research Collaborative. We used multivariable regressions to assess factors associated with lapse occurrence and duration, and compared post-lapse visual acuity by lapse duration. RESULTS Among 15,211 individuals, 71.8% experienced a lapse in care; 14.2% of the lapses lasted >24 months. Lapses were more common among non-Hispanic Black, younger, and individuals with disability, and less common in those with poor vision or prior PDR treatment. Older age and PDR treatment predicted shorter lapses, and residence in distressed areas predicted longer lapses. Visual acuity worsened after lapses, with greater declines after longer lapses. CONCLUSIONS Prolonged lapses in PDR care are common, disproportionately affect vulnerable groups, and are associated with persistent vision loss.
Diabetes care has undergone a significant transformation in the last 15 years due to the introduction of new medications and technologies. Glucagon-like peptide 1 receptor analogs (GLP-1 RA) are now a forefront drug in the treatment of type 2 diabetes and obesity ( 1, 2 ). Real-world studies have consistently shown the superiority of automatic insulin delivery (AID) over multiple daily insulin therapy in attaining optimal glucose levels in people living with type 1 diabetes (T1D) ( 3 ), leading to recommendations of offering this system to all individuals with T1D ( 4 ). However, these recommendations have not reached all of the people living with diabetes who could benefit from these innovations. The sources of disparities in access to new technologies and medications have been reported ( 5 ). Still, here we describe the absence of commercial availability of novel treatments in some countries, even in some high-income ones, as a new source of inequality.
OBJECTIVE Life expectancy of individuals with type 1 diabetes has increased, extending exposure to age-related conditions including dementia. Although earlier studies have linked type 1 diabetes with higher dementia risk, the relationships with dementia subtypes and associated risk factors are incompletely understood. RESEARCH DESIGN AND METHODS In this cohort study, 43,440 individuals with type 1 diabetes from the Swedish National Diabetes Register and 217,109 age-, sex-, and county-matched control individuals from the Swedish Total Population Register were included. Cox regression was used to study the relation between type 1 diabetes and risk of all-cause dementia and dementia subtypes (Alzheimer disease, vascular dementia, and non-Alzheimer–nonvascular dementia). We also examined the relationship between various risk factors and risk of all-cause dementia in type 1 diabetes. RESULTS After a median follow-up time of 14.3 (7.9–20.0) years, dementia was recorded in 530 (1.2%) individuals with type 1 diabetes and 1,867 (0.9%) age-, sex-, and county-matched control individuals (mean baseline age 33.0 [14.0] years). Compared with control individuals, individuals with type 1 diabetes had a higher risk of all-cause dementia (hazard ratio [HR] 2.02 [95% CI 1.83–2.23], Alzheimer disease (HR 1.38 [95% CI 1.13–1.69]), vascular dementia (HR 3.73 [95% CI 3.07–4.52]) and non-Alzheimer–nonvascular dementia (HR 1.87 [95% CI 1.63–2.15]). Risk factors related to dementia risk in type 1 diabetes beyond age were lower education level, being single, higher systolic blood pressure, higher HbA 1c, history of stroke or transient ischemic attack, history of cardiovascular disease, and longer diabetes duration. CONCLUSIONS The risk of all-cause dementia and dementia subtypes is higher in individuals with type 1 diabetes compared with matched control individuals.
OBJECTIVE The CONFIDENCE trial demonstrated additive benefits of simultaneous initiation of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, and a sodium–glucose cotransporter 2 (SGLT2) inhibitor compared with monotherapy in reducing the urinary albumin-to-creatinine ratio (UACR). This prespecified analysis evaluated whether safety and efficacy of combination therapy varies by baseline glucagon-like peptide 1 receptor agonist (GLP-1 RA) use. RESEARCH DESIGN AND METHODS Adults with chronic kidney disease (UACR ≥100 to <5,000 mg/g; estimated glomerular filtration rate [eGFR] 30–90 mL/min/1.73 m 2 ) and type 2 diabetes (glycated hemoglobin <11% [97 mmol/mol]) were randomized (1:1:1) to once-daily finerenone, empagliflozin, or finerenone plus empagliflozin. RESULTS Among 800 participants, 182 (23%) used a GLP-1 RA at baseline. At day 180, UACR change from baseline in participants using a GLP-1 RA was −51% (95% CI −59 to −40%) with combination therapy, −34% (−48 to −18%) with finerenone, and −36% (−48 to −21%) with empagliflozin. Corresponding results in those not using a GLP-1 RA at baseline were −56% (−62 to −50%), −37% (−45 to −28%), and −33% (−41 to −23%), respectively. Hyperkalemia incidence rates with combination therapy were 9.0% and 9.5% among individuals with and without baseline GLP-1 RA use. eGFR changes were consistent among individuals with and without baseline GLP-1 RA use. Acute kidney injury was uncommon. Decreases in systolic blood pressure were observed and were more pronounced with combination therapy. CONCLUSIONS In CONFIDENCE, simultaneous initiation with finerenone and an SGLT2 inhibitor was effective and well tolerated compared with monotherapy, irrespective of background use of a GLP-1 RA.
OBJECTIVE Diabetes prevention in real-world settings is affected by the challenge of intervention adherence and difficulty in sustaining behavior change. This study evaluated the effectiveness of a stepped care prevention program, enhanced with financial incentives, in reducing the risk of diabetes conversion in a multiethnic prediabetes cohort in Singapore. RESEARCH DESIGN AND METHODS The Pre-Diabetes Interventions and Continued Tracking to Ease Out Diabetes (Pre-DICTED) trial was a randomized controlled trial involving 751 overweight or obese individuals with impaired glucose tolerance, impaired fasting glucose, or both. Participants were assigned to standard care (control arm) or a stepped care intervention program, starting with lifestyle interventions for 6 months before adding metformin for participants who remained at high risk of diabetes conversion based on study visit assessments. Intervention arm participants also received financial incentives for attending lifestyle sessions and for achieving ≥5% weight loss. The primary end point was the proportion of participants developing diabetes at 3 years in the modified intention-to-treat population. RESULTS After 3 years, 34.8% of participants in the intervention arm developed diabetes compared with 47.3% in the control arm (adjusted risk difference −10.93%; 95% CI −18.04 to −3.81; P = 0.003). The adjusted relative risk was 0.74 (95% CI 0.62–0.88; P < 0.001). In the intervention arm, 26.4% of participants received metformin, and 45.1% received cash incentives. Adverse events were more common in the intervention arm, mainly because of metformin-related gastrointestinal symptoms. CONCLUSIONS A stepped care diabetes prevention program, enhanced with financial incentives, effectively reduced diabetes conversion in a multiethnic Asian prediabetes cohort.
OBJECTIVE To describe the prevalence and incidence of electrocardiogram (ECG) abnormalities and ECG-derived cardiovascular autonomic neuropathy (CAN) in the GRADE cohort of adults with type 2 diabetes (T2D) <10 years. RESEARCH DESIGN AND METHODS Individuals with T2D taking metformin alone were randomly assigned to add insulin glargine, glimepiride, liraglutide, or sitagliptin. Resting ECGs were completed at the baseline, 2-year, and 4-year study visits and analyzed for minor and major abnormalities and CAN assessed with heart rate variability (HRV) in 4,769 participants. Incidence of new major, minor, and any ECG abnormalities and CAN by treatment group was analyzed using logistic repeated-measures models at years 2 and 4 adjusted for baseline risk factors. RESULTS At baseline, participants were a mean age of 57.2 ± 10.0 years, 36.3% were women, mean diabetes duration was 4.3 ± 2.8 years, and mean HbA 1c was 7.5 ± 0.5%. Participants with ECG abnormalities at baseline (57.1%) and ECG-derived CAN (52.8%) were older and had more severe cardiovascular risk factors. The incidence of minor and major ECG abnormalities was similar among all treatment groups. However, at year 4, major ECG abnormalities were fewer in the liraglutide versus nonliraglutide groups (9% vs. 13%; P = 0.03). The incidence of CAN did not differ between the liraglutide and nonliraglutide groups across visits ( P = 0.42); however, one measure of HRV (SD of normal-to-normal R-R intervals) was higher at year 2 in the liraglutide versus nonliraglutide groups ( P = 0.02). CONCLUSIONS ECG abnormalities, including those reflecting CAN, are common in individuals with T2D <10 years and more so in those with certain cardiovascular risk factors. The development of major ECG abnormalities may be lower with liraglutide.
OBJECTIVE The objective of this study was to develop and internally validate a mathematical model of the relationships between patient clinical and social risk factors and outcomes using data from a multiethnic population with type 2 diabetes. RESEARCH DESIGN AND METHODS We constructed an incidence cohort of all adults (18 years or older) with newly diagnosed type 2 diabetes in the Kaiser Permanente Northern California (KPNC) health care system between 2005 and 2016 ( n = 129,000), following patients for at least 1 year, but up to 12 years. Using this cohort, we modeled 17 distinct diabetes-related outcomes related to micro- and macrovascular disease, as well as atrial fibrillation, depression, dementia, relevant biomarkers, and mortality. RESULTS Data were randomly split into 50%, 25%, and 25% samples to perform model estimation, calibration, and validation, respectively. Empirical and simulated data were similar for the events and biomarkers, but some factors required calibration. After calibration, they closely aligned with empirical estimates. CONCLUSIONS The resulting Diabetes Outcome Model of the U.S. (DOMUS) is a major step forward in understanding diabetes progression and the role of social determinants of health. This model can be used by scientists, policymakers, and health system managers to better understand how choices can affect population health and health disparities, including the broad diversity of U.S. races and ethnicities. Moreover, this model can be used to realize longer-term comparative effectiveness in cost-effectiveness analyses for diabetes management in the future.
OBJECTIVE Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents silently and is not routinely screened. It is associated with markedly lower HbA 1c for the prevailing glucose levels. Since HbA 1c is internationally recommended to diagnose and manage type 2 diabetes (T2D), we investigated the population-level impact of undiagnosed G6PD deficiency on T2D diagnosis and complications in the U.K. RESEARCH DESIGN AND METHODS We used whole-exome sequencing and electronic health record data from UK Biobank ( n = 467,368) and Genes & Health ( n = 43,011) cohorts. RESULTS In the U.K., we estimated that ∼1 in 7 Black and 1 in 63 Asian males carry G6PD deficiency alleles, compared with fewer than 1 in 10,000 White males. Despite this, less than 1 in 50 G6PD‐deficient men are clinically recognized. Male G6PD carriers have considerably lower average HbA 1c (0.9% [International Federation of Clinical Chemistry and Laboratory Medicine: 10.0 mmol/mol]) compared with noncarriers, while differences in average glucose were negligible. G6PD‐deficient men had 1.37 (95% CI: 1.01, 1.86) higher odds of developing diabetes‐related microvascular complications than noncarriers. Although risk factors were similar prior to diagnosis, male G6PD carriers diagnosed with T2D since 2011 were, on average, 4.1 years (95% CI: 0.6, 7.7) older at diagnosis compared with noncarriers. In addition, lower mean HbA 1c values in G6PD carriers falsely underestimated their 10‐year T2D risk. CONCLUSIONS Undiagnosed G6PD deficiency has significant impact on T2D diagnosis with HbA 1c and associates with increased risk of diabetes complications. This has major implications for global populations using HbA 1c for diagnosis and monitoring, and could contribute significantly to inequalities in diabetes outcomes.
With no clear idea of what he wanted to do with his life, it was an ironic turn of fate that drew Frank B. Hu to medicine. “I was studying for my college entrance exam—a very stressful time—and I suddenly felt unbearable pain. A severe stomach ache,” he says. The pain eventually subsided, but while in the emergency room, the kindness he was shown by hospital staff left an impression. “When you’re young, you don’t really think about health care,” he says. “But seeing the system up close, having a positive experience—it made an impact.”
Medical News
15th Jan, 2026
phys.org
Wiley
What's New: Drugs
FDA
Surgery
Journal of the American Medical Association
