Background: Up to 40% of adult individuals with Cystic Fibrosis (CF) develop a condition known as Cystic Fibrosis Diabetes (CFRD). This co morbid condition, is secondary to insulin deficiency as a result of pancreatic islet cell damage subsequent to the underlying genetic mutation in CF. CFRD is associated with the development of microvascular complications however, little is known about the prevalence of neuropathic dysfunction in the form of cardiac autonomic neuropathy (CAN). This study examined the extent of CAN in an adult population with CF dysglycemia compared to a population with CF and normal glucose tolerance. Methods: We performed a cross-sectional study comparing three parasympathetic function tests on 71 adults with CF, 46 of whom had CF dysglycemia. Healthy volunteers were the control group. Results: There was no significant difference between the CF cohort with normal glucose tolerance and the CF cohort with dysglycemia in all three measures of parasympathetic function. Older individuals with dysglycemia were more likely to demonstrate a lower heart rate variability only in the deep breathing measurement (p<0.01) compared to the healthy control group. The presence of dysglycemia was not an influential factor in heart rate variability in the Valsalva maneuver and standing compared to CF individuals with normal glucose tolerance. Conclusion: Based on these findings, the presence of dysglycemia in CF may not be a major influential factor in the development of parasympathetic cardiac dysfunction in CF. However, heart rate variability during deep breathing was lower in CF dysglycemia compared to those with normal glucose tolerance and was significantly reduced compared to healthy controls. This suggests longitudinal studies are needed to evaluate the long-term impact of dysglycemia in cardiac autonomic neuropathy in Cystic Fibrosis.
Objective: This study investigated clinical inertia in the management of type 2 diabetes mellitus (T2DM), a major challenge in clinical practice. The primary aim was to assess the delay in therapeutic intensification among patients with persistently elevated hemoglobin A1c (HbA1c) levels (>8.0%) who were already receiving two oral antidiabetic drugs, considering the availability of newer effective therapies. Research design and methods: We conducted a retrospective cohort study using data from the Clalit Health Service database in Israel. The initial cohort comprised 554 patients with T2DM and HbA1c >8.0%, of whom 518 managed by general practitioners were included in the primary analysis. Patients were stratified into two subgroups: HbA1c >8% to ≤9% and HbA1c >9%. Data were analyzed to determine the timing, type, and effectiveness of treatment intensification decisions over up to 18-month follow-up period. Results: Therapeutic intensification with a third medication occurred in 58.4% of patients with HbA1c >9% compared to 47.4% of those with HbA1c >8% to ≤9% (p = 0.012), with shorter median time to intensification in the less controlled group (6.4 vs 10.3 months respectively, p = 0.034). The most common form of intensification was the addition of a third oral agent (79.2% vs. 53.4%, p <0.001). Injectable therapies were used less frequently, and insulin was preferred over glucagon-like peptide-1 receptor agonists (GLP-1Rs) (32.9% vs. 11.8% for insulin, p <0.001; 16.4% vs. 10.2% for GLP-1RAs, p = 0.137). Despite intensification, many patients did not achieve their glycemic targets. Conclusions: Clinical inertia represents a significant barrier to effective T2DM management. Targeted educational interventions are urgently needed to improve adherence to current clinical guidelines among primary care physicians.
Background: Screening for type 1 diabetes (T1D) can be challenging, causing diagnostic delay and potentially serious health consequences. Continuing education (CE) in T1D is lagging but could help improve clinician knowledge of and engagement in T1D screening behaviors. Materials and methods: This retrospective, case-control study assessed pre-/post-changes in clinician knowledge of T1D screening and management (N=4817) following exposure to an interactive, multicomponent CE program (DETECT T1D) from May 2024 to January 2025. Using medical claims, it evaluated pre/post practice change by comparing learners and matched non-learner controls (N=9361) on T1D screening behaviors during the 12 months pre-education vs all available month’s post-education through May 2025.x Results: Post-education, learners demonstrated multiple knowledge and competence gains, including understanding the T1D presentation in adults versus children and identifying appropriate autoantibody screening strategies. Learners achieved a 54% increase in screenings (i.e., 668 more new screenings) following DETECT T1D education vs non-learners (1913 new screenings for learner’s vs 1245 new screenings for non-learners). Primary care, pediatric, and advanced practice provider learners in particular achieved a 116 % gain in screenings vs non-learners (715 new screenings vs 332 new screenings). Learners across all specialties and in all geographic regions demonstrated gains in new screenings vs non-learners. Conclusion: Interactive, immersive, multicomponent CE may be a feasible and effective pathway to improving clinician detection of T1D. Exposure to this type of learning could have positive downstream effects for patients in terms of more timely diagnosis and earlier intervention, including with disease-modifying therapies that can delay T1D clinical progression.
Sato’s article “Decline in Physical Activity after Age 35 Increases the Risk of Obesity, Insulin Resistance, and Diabetes” highlights the obesity and diabetes crises, offering strategies to mitigate these illnesses through health promotion programs and personal motivation. To promote population behavior change, approaches that include societal, structural and personal influences are imperative. This commentary adds to Sato’s recommendations, while providing a broader public health perspective that could help health leaders curb the trajectory of the obesity and diabetes epidemics.
Background: Overlap between diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) is associated with significantly higher mortality than either condition alone. While hypertonic (trans locational) hyponatremia is common in hyperglycemic crises, clinically significant hypernatremia in mixed DKA/HHS presents with certain treatment challenges due to rapid osmotic shifts during insulin therapy. Case presentations: A 40-year-old woman with non-significant past medical history presented with vomiting, polyuria, polydipsia, and confusion for two days. Laboratory evaluation revealed serum glucose 1280 mg/dL, arterial pH 7.214, bicarbonate 13.1 mmol/L, anion gap 24, β-hydroxybutyrate 6.0 mmol/L, corrected sodium 152 mmol/L (measured sodium 133 mmol/L), and calculated effective osmolality 337 mOsm/kg. Initial treatment with isotonic saline and intravenous insulin led to improvement in hyperglycemia but worsening corrected hypernatremia to 160 mmol/L after 3 liters of normal saline. Free water deficit was calculated at 6.3 L. Fluid therapy was transitioned to hypotonic solutions with titration to limit sodium correction to ≤10 mmol/L per 24 hours. Sodium levels gradually normalized with resolution of ketoacidosis, and improvement in mental status without significant neurologic complications. Conclusion: In mixed DKA/HHS, early assessment of corrected sodium and effective osmolality is critical. Insulin-mediated intracellular water shifts may unmask or worsen hypernatremia. Prompt reassessment of corrected sodium and individualized fluid management is needed to avoid treatment-related exacerbation of hypertonicity.
Background: The aim of this study was to evaluate the long-term effects of continuous subcutaneous insulin infusion (CSII) therapy on the improvement of metabolic control and beta-cell function in patients with type 2 diabetes mellitus. Methods: A single-center retrospective observational study was carried out in patients with T2DM who required CSII therapy due to suboptimal glycemic control. T2DM patients treated with the DANA-R Diabe care insulin pump (SOOIL Development Co., Ltd.) was followed for 6 years. Glucose control measures (hemoglobin A1c, total daily insulin dose) and beta-cell function (c-peptide index, insulinogenic index) were analyzed and clinical outcome data (body mass index, systolic/diastolic blood pressure, hemoglobin, serum protein, serum albumin, serum creatinine, total cholesterol, triglyceride, HDL, and LDL) were assessed after 2,4, and 6-years use of CSII. Statistical significances were calculated by Student’s paired t-test. Results: Fifty-seven T2DM patients with mean age of 58.2±1.1 years were included in the study with 6 years (75.1±5.0 months) of follow-up. We found a statistically significant improvement in glycated hemoglobin (7.7±0.2, 6.3±0.1, 6.3±0.1, and 6.5±0.1%, p<0.0001), total daily insulin dose (48.6±3.1, 39.7±2.9, 34.2±2.0, and 34.4±2.2 U/day, p<0.0001), c-peptidogenic index (0.28±0.03. 0.42±0.07, 0.32±0.04, and 0.38±0.07, p<0.05), and insulinogenic index (3.28±0.53, 8.62±1.09, 6.47±0.74, and 5.84±0.96, p<0.001) after 2, 4, and 6-years use of CSII, respectively. Additionally, there were differences in clinical outcomes such as serum protein, albumin, total cholesterol, triacylglycerol, HDL, and LDL after 6 years. Conclusions: The use of long-term CSII therapy for patients with T2DM led to a statistically significant and sustained improvement in glycemic control and beta-cell function.
Inflammation is a key factor in retinal damage in response to diabetes. Sortilin represents a new regulator of retinal inflammation. Sortilin is involved in over 50 different signaling cascades. To investigate sortilin in the diabetic retina, we first measured protein levels in retinal lysates from diabetic humans and diabetic mice. We then inhibited sortilin using a small molecule inhibitor, AF38469, and evaluated retinal function using electroretinogram (ERG) and fluorescein angiography. We also measured key inflammatory and autophagic proteins. Data showed that sortilin levels were significantly increased in retinal lysates from diabetic patients and diabetic mice. Treatment of mice with AF38469 in their drinking water restored ERG and angiography to normal levels in diabetic mice. We found that AF38469 reduced high mobility group box 1 (HMGB1) and interleukin-1beta (IL-1β) levels. We also found that inhibiting sortilin led to reduced LAMP2 levels in diabetic mice. In conclusion, our data suggest that inhibition of sortilin may offer a new pathway to protect the diabetic retina.
Individuals with type 1 diabetes are more vulnerable than the general population to morbidity and mortality from infectious disease, including COVID-19. Over the last 20 years, the >100-year-old tuberculosis vaccine, known as Bacille Calmette-Guerin (BCG), has been observed in global populations to protect from viral, bacterial and parasitic infections, among others. Our laboratory conducted the first and only trials in type 1 diabetics (T1Ds) to determine whether infectious disease protection could be conferred by multi-dose BCG vaccine as an immunotherapy. In two back-to-back randomized, placebo-controlled, double-blinded trials covering the entire course of the COVID-19 pandemic, we found that up to six doses of BCG were safe and protected against developing COVID-19 and other infections. Like other BCG-related off-target effects, these benefits took a minimum of 3 years to begin to materialize, yet they potentially may last for decades. A total of 12 worldwide clinical trials have evaluated largely single-dose BCG vaccines for COVID-19 prevention in other high-risk populations, like the elderly and health care workers. Five found BCG to be efficacious, while seven did not. The BCG trials that failed to find benefit were often too short in duration to obtain protection. We show, in a US T1D population, that full infectious disease protection takes up to 5 years. Also, many negative trials testing BCG efficacy were actually BCG booster (re-vaccination) trials in which placebo groups had also received prior neonatal BCG vaccines, thereby obscuring the possibility of finding a large benefit in the treatment group. Further, not all clinical trials utilized the most potent BCG strains. On the basis of our successful trials of multi-dose BCG in a vulnerable US population of T1D subjects, we conclude that this population stands to benefit from multi-dose BCG immunotherapy for protection from COVID-19 and other infectious diseases.
Sesame (Sesamum indicum L) has garnered attention for its potential in diabetes management due to its rich bioactive compounds, including sesamin, sesamolin, and unsaturated fatty acids. This commentary explores recent advances in sesame research, emphasizing its role in improving glycemic control, lipid profiles, inflammation, and oxidative stress, as evidenced by a systematic review and meta-analysis. Mechanistic insights reveal sesame’s effects on PPARα activation, Nrf2 signaling, and NF-κB suppression, which underpin its metabolic benefits. Recent trials across diverse populations demonstrate the efficacy of sesame oil, seeds, paste, and sesamin supplements in reducing HbA1c, fasting glucose, and cardiovascular risk factors. However, challenges such as study heterogeneity, limited generalizability, and unclear optimal dosing hinder clinical translation. Future research should prioritize large-scale, long-term RCTs, mechanistic studies on gut microbiota and neuroprotection, and personalized nutrition approaches to fully harness sesame’s therapeutic potential in combating the global diabetes epidemic.
Clinical laboratories are pivotal in modern healthcare, providing essential diagnostic information that influences patient management and healthcare efficiency. Technological advancements and economic pressures have continuously shaped laboratory medicine, leading to significant transformations in diagnostic capabilities. This article explores the evolving role of clinical laboratories, emphasizing their impact on disease prevention, early diagnosis, and patient safety. The discussion highlights the challenges faced by laboratory professionals, including test selection, result interpretation, and communication gaps between clinicians and laboratorians. Laboratory errors, classified into cognitive, systematic, and no-fault categories, are examined along with strategies to solve them. The importance of evidence-based laboratory medicine (EBLM), quality improvement initiatives, and inter-professional collaboration is not well understood. Furthermore, the integration of artificial intelligence in laboratory processes is considered a promising advancement, enhancing diagnostic accuracy and efficiency. The article concludes that encouraging effective communication and collaboration between laboratory personnel and clinicians is essential for optimizing patient care and ensuring the continued evolution of laboratory medicine.
Objective: To investigate the impact of changes in physical activity from young adulthood (ages 20–35 years) to middle age (ages ≥35 years) on the prevalence of obesity, insulin resistance, and diabetes. Research design and methods: Data were analyzed from 1,395 participants in the Midlife in the United States (MIDUS) study, including biomarker subsamples. Participants reported their physical activity levels during young adulthood and currently (≥ 20 min, three times per week). Participants were categorized as persistently active, increased, decreased, or persistently inactive. Obesity was defined as body mass index (BMI) ≥ 30 kg/m², insulin resistance by HOMA-IR ≥ 2.8, and diabetes by self-reported diagnosis. Multivariable logistic regression was used to assess associations. Results: Participants with decreased or persistently low physical activity levels were significantly more likely to have obesity (OR 2.29 and OR 2.03, respectively), insulin resistance (OR 1.88 and OR 1.79, respectively), and diabetes (OR 1.79 and OR 1.73, respectively) compared to persistently active subjects. After adjusting for covariates, including age, income, and alcohol consumption, increased activity did not exhibit a significant protective effect compared to persistent activity. Conclusions: A decline in physical activity after the age of 35 years is associated with higher risks of obesity, insulin resistance, and diabetes. Health promotion programs targeting the maintenance of regular physical activity in adulthood may reduce these risks. Further longitudinal studies are needed to confirm these findings and address limitations, including sample diversity and missing data.
The purpose of this study is to evaluate the effect of ultraviolet UV photo functionalization on the antimicrobial properties in implants installed in patients with type 2 diabetes mellitus. The study included 74 patients with diabetes with unilateral/bilateral missing teeth (aged 36 to 63 years). The participants were randomly divided into 2 groups; Group-A included 38 patients with UV photo functionalized 204 implants and Group-B included 36 patients with non UV photo functionalized 183 implants. The clinical parameters of the dental implants were evaluated by assessing PD, BOP, MBL 6 months, 12 months, and 3 years after implant installation, compared with values at last follow-up. Concentrations of interleukin IL-1β and TNF-α cytokines in blood serum were evaluated using enzyme-linked immunosorbent assay. After implant surgery, the patients in Group-A had minimal postoperative reactions including swelling, discoloration, discomfort, hematomas. After implant surgery, the patients in Group-B had a mild postoperative reaction including swelling and discomfort. Preoperative serum IL-1β levels and TNF-α in Group-A and Group-B patients did not differ significantly. After implant surgery indicators of cytokines markers show correlation with Group-A and Group-B, the rates of IL-1β levels and TNF-α are higher in patients of Group-B. Analysis of the results showed the greatest increase in the rates of IL-1β levels and TNF-α in peri-mucositis and peri-implantitis. The survival rate of implants in Group A patients is 97.3% and in Group B patients is 94.2% after five-years. The results of the study showed that monitoring levels of the cytokines TNF-α and IL-1β may aid in the early diagnosis of peri-implantitis and prognosis in high-risk patients with type 2 diabetes mellitus.
Introduction: Diabetes mellitus (DM) is an important chronic comorbid condition that occurs in people living with the human immunodeficiency virus (HIV). It is associated with increased morbidity and mortality. Many cases of comorbidities with diabetes mellitus have been reported, particularly in areas of the world where the prevalence of HIV is high. The rate of diabetes hospitalizations among HIV-infected individuals increased from 3.9 to 8.4 per 100 hospitalizations. Although the cost of HIV care has increased, the burden of DM among people living with HIV has economic consequences. Objectives: This study aimed to assess the incidence of DM among HIV patients receiving ART in the Asella Referral and Teaching Hospital, Oromia Regional State, Ethiopia. Methods: Ten years retrospective follow-up study was conducted among 268 HIV patients receiving ART at Asella Referral and Teaching Hospital. HIV patients receiving ART between January 01/2013 and Dec 31/2022 were enrolled in this study. A systematic sampling technique was used to select patients’ medical charts. Data were extracted from the patients’ medical chart records from March 21 to March 23, 2023, using a data extraction format. Data were entered into Epi Data version 4.6.0.0, and exported to STATA version 14.2 for statistical analysis. Results: A total of 268 medical charts of HIV patients receiving ART were included in the final analysis, which provided a response rate of 98.52%. The mean age of participants was 38.17 years. Among 268 HIV patients followed for 10 years, 142 (52.99%) were female, 33(49.63%) were aged between 30-40 years. Approximately 154 (57.46%) of them were urban residents. The incidence density rate (IDR) of DM in the cohort of HIV patients receiving ART during 1291.33 person-year observation was 6.20 per 1000 [95% CI: 3.10, 12.39] person-years. The cumulative incidence proportion of DM among HIV patients receiving ART was 2.99% [95% CI: 1.49, 5.88] within the 10 years follow-up period. Conclusion: The incidence of DM among HIV patients receiving ART was relatively high. It is important to emphasize HIV patients receiving ART for early screening of DM among these patients.
Background: Whether any of the anthropometric indices are associated with cardiometabolic outcomes in indigenous Fulani African populations is not known. This study assesses anthropometric indices in predicting cardiometabolic outcomes in indigenous and non-indigenous populations. Methods: A population-based cross-sectional study recruited 1921 participants from the settled Fulani, nomadic pastoral Fulani and the general population. Body weight (BW), height, waist circumference (WC), and hip circumference (HC) were measured and body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), Conicity Index (Cindex), body adiposity index (BAI), body roundness index (BRI) and body shape index (ABSI) were determined. The associations of anthropometric indices with cardiometabolic disorders were assessed by multivariable adjusted logistic regression and the area under the receiver-operating characteristic curve compared the predictive abilities. Results: In women, BW and BMI showed good performance in identifying dysglycaemia in Fulbe and general population. In men, WC, HC and BRI, and WC and BRI had good performance in all groups to predict hypertension and dysglycaemia/hypertension respectively. All the anthropometric indices showed good performance to identify MetS. Conclusion: With transition from nomadic to settled life indigenous Fulani are at greater risk for MetS. Adiposity indices for identification of cardiometabolic disorders vary by ethnicity and sex. WC, WHtR and BRI are better anthropometric indices to identify MetS in indigenous Fulani population.
Background: Diabetes mellitus is a metabolic disorder characterized by high blood glucose levels due to insulin irregularities. It is frequently accompanied by difficulties in the metabolism of carbohydrates, fats, and proteins. Despite the significant loss of life and resources associated with DM, management remains insufficient. This management typically involves pharmacologic interventions and lifestyle modifications (LSM). However, a majority of patients and caregivers tend to disregard LSM in the management of type 2 diabetic patients. Objective: To assess lifestyle modification practice and associated factors among type 2 diabetic patients in selected North Shewa Public Hospitals, Oromia, Ethiopia. Methods: A hospital-based cross-sectional study design was conducted in North Shewa Zone public hospitals among 407 randomly selected type 2 diabetic patients from September 1 to November 30, 2022. Data were collected using a structured and pre-tested interviewer-administered questionnaire entered into Epidata version 3.1 and then exported to SPSS version 24 for statistical analysis. Descriptive, bivariate, and multivariate binary logistic regression analyses were done using SPSS. Results: The overall magnitude of good lifestyle modification practice among type 2 diabetic patients was 41.5 % [95% CI: (36.7, 46.3)]. In the multivariable logistic regression analysis attending secondary, college and above education (AOR = 3.73, 95% CI: 1.56–8.92) and (3.995% CI: 1.71–8.90), respectively, urban dwellers (AOR = 3.19, 95% CI: 1.65–6.17), respondents who had no diabetic related comorbidities (AOR = 3.17, 95% CI: 1.85–5.44), and patients who got LSM education (AOR = 2.37, 95% CI: 1.44–3.92) were significantly associated with good lifestyle modification practice. Conclusion: The prevalence of poor lifestyle modification practice was observed in more than fifty per cent of the patients. LSM practice was good among high educational levels, urban dwellers, those not having diabetic comorbidities, and those with diabetic LSM education.
Background: Hyperglycemia, characterized by elevated blood glucose levels, often leads to diabetes mellitus and severe complications if unmanaged. Globally, hyperglycemia is a pressing public health issue, exacerbated by increasing diabetes prevalence. In sub-Saharan Africa, including Ghana, the rise in diabetes cases is alarming, necessitating urgent health interventions. Concurrently, dyslipidemia, marked by abnormal lipid levels, contributes significantly to cardiovascular diseases. This study aims to investigate the comorbidity of hyperglycemia and dyslipidemia among factory workers in an urban center in Ghana, providing insights into this high-risk group's health status. Methods: Conducted between January 2023 and December 2023 at a food processing factory in Tema, Ghana, this cross-sectional study included 230 participants. Blood samples were analyzed for glucose and lipid profiles using automated chemistry analyzers. Statistical analyses were performed using SPSS software to assess glucose and lipid parameters, and their prevalence was compared across age and gender groups. Results: The study revealed a gender imbalance with 93% males and 7% females. Most participants (62.2%) were over 40 years old. Hyperglycemia prevalence was 10.9%, predominantly affecting those over 40. Dyslipidemia was observed in 65.7% of participants, with low-density lipoprotein cholesterol (LDL-c) being the most prevalent abnormality. Comorbidity of both hyperglycemia and dyslipidemia was notably higher in individuals over 40 years. Conclusion: This study highlights significant health issues among factory workers, including high rates of dyslipidemia and hyperglycemia, particularly in older adults. The findings underscore the need for targeted health interventions to manage these conditions and mitigate cardiovascular risk, emphasizing the importance of preventive measures and regular health screenings in occupational settings.
Eph B1/Ephrin B1 signaling has been shown to play a role in inflammation and pain in some targets; however, its upstream regulation is less clear. To investigate whether exchange protein for cAMP1 (Epac1) can regulate EphB1/ephrin B1 in retinal Müller cells, we generated Epac1-Müller cell specific knockout mice. We used protein analyses to show that Epac1 regulates both EphB1/ephrin B1, as well as high mobility group box 1 (HMGB1) and NLR family pyrin domain containing 3 (NLRP3). Overall, these studies demonstrate the loss of Epac1 in retinal Müller cells increased protein levels of EphB1/ephrin B1, as well as HMGB1 and NLRP3. These mice can be used for future studies on these pathways.
The glucagon-like peptide 1 receptor (GLP-1R) agonist semaglutide is effective for the treatment of obesity and type 2 diabetes mellitus (T2DM). The purpose of this article is to define the therapeutic role of semaglutide for obesity-related heart failure with preserved ejection fraction (HF-pEF). Methods: Critical review of 2 recent randomized trials, the Subjects with Obesity-related Heart Failure with Preserved Ejection Fraction (STEP-HFpEF) and STEP-HFpEF DM. The latter 2 studies had similar design and endpoints that evaluated efficacy and safety of semaglutide 2.4 mg/w in obese subjects without and with T2DM, respectively. The 2 primary endpoints were the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and the percentage change in body weight. After 52 weeks, placebo-corrected amelioration in the KCCQ-CSS was similar in subjects without and with diabetes, 7.8 points (95% CI, 4.8 to 10.9; P<0.001) and 7.3 points (95% CI, 4.1 to 10.4; P<0.001), respectively. However, placebo-corrected weight loss appeared more marked in subjects without diabetes, -10.7 percentage points (95% CI, -11.9 to -9.4; P<0.001) but -6.4 percentage points (95% CI, -7.6 to -5.2; P<0.001) in patients with diabetes. In both trials, semaglutide improved the 6-minute walking distance (6-MWD) albeit more so in subjects without diabetes with placebo-adjusted difference of 20.3 meters (m) (95% CI, 8.6 to 32.1, P<0.001) and 14.3 m (95% CI, 3.7 to 24.9; P< 0.0001) in subjects without diabetes and with diabetes, respectively. In addition, semaglutide decreased levels of C-reactive protein (CRP) similarly in patients with and without diabetes. In the diabetes trial, the effects of semaglutide on the KCCQ-CSS and weight reduction were attenuated in patients receiving sodium-glucose co-transporter 2 (SGLT2) inhibitors. Subgroup analysis of pooled data from the 2 trials suggested that beneficial effects of semaglutide on the KCCQ-CSS might be more evident in patients with more advanced HFpEF. Adverse effects led to semaglutide discontinuation in 12% of patients compared with 7% with placebo. The most common cause of semaglutide discontinuation was gastrointestinal (GI) disorders. Overall, semaglutide improved physical performance and reduced weight in obese subjects with HF-pEF with and without diabetes. Long-term randomized trials are needed to evaluate the effects of semaglutide on cardiovascular (CV) events and mortality in obesity-related HF-pEF.
Whether sodium-glucose co-transporters-2 (SGLT2) inhibitors have beneficial effects on cardiovascular (CV) events and mortality if given within few days from acute myocardial infarction (AMI) is unknown. The DAPA-MI trial (n= 4,107) is the only available study designed to evaluate the impact of administration of dapagliflozin on CV outcomes and mortality if started within 10 days from occurrence of an AMI. Using the win-ratio approach, the primary outcome of the DAPA-MI trial was the hierarchical composite of death, hospitalization for heart failure (HFF), nonfatal myocardial infraction (MI), atrial fibrillation/flutter, incident type 2 diabetes, New York Heart Association Functional Class (NYHAFC) at the last visit, and weight decrease of 5% or greater. After a median duration of follow-up of 11.6 months, the win ratio was in favor of dapagliflozin being 1.34 (95% CI, 1.20 to 1.50, P< 0.001). This improvement in win ratio was mainly attributed to weight reduction (-1.65 kg versus placebo), 47% lower rates of incident type 2 diabetes [hazard ratio (HR) 0.53, 95% CI, 0.36 to 0.77)], and mild amelioration in NYHAFC. However, there was tendency toward increase in all-cause death (HR 1.22, 95% CI, 0.77 to 1.92), CV death (HR 1.15, 95% CI, 0.66 to 2.01), all-cause hospitalization (HR 1.12, 95% CI, 0.98 to 1.29), and non-fatal MI (HR 1.11, 95% CI, 0.72 to 1.71) with dapagliflozin. In the EMMY trial, empagliflozin when initiated within 3 days of percutaneous coronary intervention (PCI) in patients with AMI decreased serum levels of N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP) by 15% and marginally improved left ventricular ejection fraction (LVEF) by 1.5% compared with placebo. The ongoing EMPACT-MI trial should clarify the effects of empagliflozin on hard CV outcomes and mortality in patients with recent AMI. In conclusion, current data suggests that early use of SGLT2 inhibitors within days after acute MI may reduce incidence of type 2 diabetes and body weight, but it was associated with a trend toward increased all-cause death, CV death, and MI. Further studies are needed before recommending the early initiation of SGLT2 inhibitors following AMI.
