Diabetes Therapy最新文献

Introduction: To evaluate real-world hemoglobin A1c (HbA1c) and weight change in adults initiating treatment with tirzepatide (dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist [GLP-1 RA]) or injectable semaglutide (GLP-1 RA) indicated for type 2 diabetes (T2D) management.

Methods: This retrospective analysis utilized the Healthcare Integrated Research Database® to identify adults with T2D starting tirzepatide or injectable semaglutide between May 13, 2022 and May 29, 2023. GLP-1 RA naïve and non-naïve cohorts were identified based on the history of GLP-1 RA use within ≤ 6 months of initiation. Propensity score matching balanced 6-month baseline characteristics between groups. HbA1c and weight changes were assessed from initiation to 12 months for matched patients with HbA1c and weight data at both time points.

Results: Both matched naïve cohorts were comprised of 10,702 patients (tirzepatide: 1399 with HbA1c data and 454 with weight data; semaglutide: 1173 with HbA1c data and 432 with weight data). Mean baseline HbA1c and weight were 7.8% and 112.4 kg, respectively, for the tirzepatide group and 7.8% and 110.7 kg for the semaglutide group. Both matched non-naïve cohorts were comprised of 5577 patients (tirzepatide: 792 with HbA1c data and 296 with weight data; semaglutide: 738 with HbA1c data and 224 with weight data). Mean baseline HbA1c and weight were 7.7% and 112.5 kg for tirzepatide, and 7.9% and 108.5 kg for semaglutide. Tirzepatide was associated with greater mean reductions in HbA1c (naïve: - 1.3% vs. - 0.9%; non-naïve: - 0.9% vs. - 0.6%; p < 0.001) and weight (naïve: - 10.2 kg vs. - 6.1 kg; non-naïve: - 7.9 kg vs. - 3.7 kg; p < 0.001) than semaglutide.

Conclusions: Patients with T2D starting tirzepatide had greater HbA1c and weight reductions at 12 months post-initiation than those on injectable semaglutide, regardless of previous GLP-1 RA use, consistent with previous clinical trial results.

Introduction: Basal insulin injections have historically been administered via once-daily (OD) or twice-daily (BD) injections. Once-weekly (OW) basal insulin injections have recently been developed. This study aimed to quantify the relative importance of the administration frequency in basal insulin treatment preferences of people living with T2D in Canada, Spain, France, and Japan, using a discrete choice experiment (DCE).

Methods: Best-practice guidelines for patient preference studies were followed in a three-phase study design. Phases one (targeted literature review) and two (qualitative interviews) informed the development of an attributes and levels grid. Phase three consisted of pilot interviews to evaluate the feasibility of preference survey completion and DCE tasks among adults living with T2D across Canada, France, Spain, and Japan. Hierarchical Bayesian estimation was used to estimate part-worth utilities for attribute levels, then calculate the relative importance of each attribute among other attributes tested.

Results: The DCE survey was completed by N = 513 participants (aged 20-90; 54% male, 45% female; mean time since diagnosis: 11.6 years). Participants were split into three treatment groups: basal insulin and injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) naïve (n = 176), basal insulin naïve but with injectable GLP-1 RA experience (n = 176) and basal insulin experienced (n = 161). The administration frequency had a relative importance of 40% across the full sample, double that of any other treatment attribute tested in this study. A preference for OW administration was found relative to OD and BD. Findings were consistent across treatment groups and countries.

Conclusions: This study demonstrated the value and importance of administration frequency in making choices for basal insulin treatments when glycemic control is held constant. Per the pre-specified conditions, participants expressed a preference for OW basal insulin, making considered trade-offs between treatment risks (e.g., risk of a severe hypoglycemic event) and convenience (e.g., frequency of administration).

Post-bariatric hypoglycemia (PBH) is a frequent yet complex complication following Roux-en-Y gastric bypass, typically related to exaggerated insulin responses after rapid glucose absorption. Identifying alternative or contributing mechanisms is particularly challenging in this population due to altered anatomy and limited access to standard diagnostic tools. We describe the case of a 65-year-old man with a history of type 2 diabetes, obesity, and cardiac sarcoidosis, who achieved diabetes remission after gastric bypass. Several months later, he developed frequent postprandial and nocturnal hypoglycemic episodes despite strict dietary adjustments. Continuous glucose monitoring showed 38% time below range. A 72-h fasting test revealed inappropriately high proinsulin and C-peptide levels, indicating endogenous hyperinsulinemia. The patient was receiving sacubitril/valsartan for heart failure. Upon discontinuation of this treatment due to worsening renal function, hypoglycemic episodes resolved completely, and a repeat fasting test was normal. This is, to our knowledge, the first case report describing sacubitril/valsartan-associated hypoglycemia in a patient post-gastric bypass surgery, and the first to document inappropriate insulin secretion under treatment using a fasting test. Preclinical data suggest that neprilysin inhibition may enhance insulin secretion, possibly via increased GLP-1 bioavailability. While sacubitril/valsartan has demonstrated cardiovascular benefit, its metabolic effects remain underrecognized. Given the growing number of patients who have undergone bariatric surgery and the widespread use of this medication, clinicians should consider its potential role in refractory hypoglycemia. Early identification may avoid unnecessary investigations and support appropriate therapeutic adjustments.

Introduction: Diabetes represents an increasing public health challenge in France, yet national data distinguishing type 1 from type 2 diabetes and insulin use remain limited. This study aimed to describe trends in the epidemiology, care pathways and health outcomes of adult individuals living with type 1 or type 2 diabetes in France from 2010 to 2019. It focused on individuals treated or not with insulin and applied a predictive classification algorithm to accurately distinguish between diabetes types using real-world data.

Methods: A 10-year retrospective population-based cohort study was conducted from a representative one-tenth sample of the French national healthcare database (i.e. SNDS, Système National des données de Santé), covering nearly the entire French population. Adults (≥ 18 years) affiliated with the general insurance scheme were included. A machine learning algorithm, trained on clinical data from general practitioners, was applied to classify diabetes type. Annual trends in prevalence, incidence, comorbidities, treatments, outpatient care, complications and mortality were assessed.

Results: Among an extrapolated 5.5 million individuals with diabetes in 2019, 3.5% had type 1 diabetes and 96.5% had type 2 diabetes. The prevalence of type 2 diabetes increased from 6.2% in 2010 to 8.0% in 2019, while type 1 diabetes remained stable. Comorbidity rates were high and increasing in insulin-treated individuals with type 2 diabetes. In 2019, 15.3% of insulin-treated individuals with type 2 diabetes had at least one complication-related hospitalisation. Specialist consultations were underused, especially in type 2 diabetes. The mortality rate in individuals with type 1 diabetes declined from 2.6% to 1.5%, with an increase in mean age at death.

Conclusion: This national study provides updated insights into diabetes in France and highlights the need to improve access to specialised care and reinforce long-term surveillance strategies.

Introduction: There are differences in the microbiological and antimicrobial patterns of patients with diabetic foot infections (DFI) in different regions. Understanding the microbiological and antimicrobial patterns of patients with DFI in this region provides a basis for the empirical use of antibiotics in clinical practice.

Methods: This study retrospectively analyzed the clinical and laboratory characteristics and microbiological and antibacterial patterns of patients with DFI from January 2016 to December 2023.

Results: A total of 697 patients were included, with the majority being male (63.4%), and ages ranging from 50 to 75 years (59.3%). Most had poor blood sugar control (70.3%). Among them, 527 (75.6%) had single microorganism infections, while 170 (24.4%) had multiple microorganism infections. A total of 891 pathogenic strains were isolated, of which 419 (47.0%) were Gram-positive bacteria (GPB), 454 (51.0%) were Gram-negative bacteria (GNB), and 18 (2.0%) were fungi. The most common GPB is Staphylococcus aureus (196, 22.0%), while the most common GNB is Proteus mirabilis (70, 7.9%). GNB infections and multiple microorganism infections were more prevalent than GPB infections and single microorganism infections in Wagner grades 3-4. Patients with GNB infections had higher levels of ESR, WBC, NE, NEUT, PCT, and CRP, while ALB and Hb levels were lower. GPB were highly sensitive to teicoplanin (100%), followed by vancomycin (99.6%) and tigecycline (99.2%); GNB exhibited high sensitivity to sulperazon and amikacin (100%), followed by ertapenem (98.8%) and meropenem (98.6%).

Conclusion: The proportion of GNB is greater than that of GPB, primarily found in patients with moderate to severe DFI, who exhibit higher levels of inflammatory markers and more severe infections. However, S. aureus remains the most common microorganism in DFI. When using antibiotics, especially for patients with mild infections, coverage for common GPB, including S. aureus, should be considered, while for patients with moderate to severe infections, coverage should include common GNB.

Introduction: This study examines the characteristics of adults with type 2 diabetes (T2D) who were not initially treated with an antihyperglycemic agent (AHA).

Methods: The analyses used Optum de-identified Market Clarity data from January 2013 through September 2023. The US study included nonpregnant adults with T2D who were continuously insured from 1 year prior through 5 years post diagnosis and did not fill a prescription for an AHA in the year after their initial T2D diagnosis. Differences between those treated in years 2-5 with an AHA (delayed treatment) and those untreated with an AHA for 5 years post diagnosis (untreated) were examined descriptively and using multivariable analyses.

Results: Out of 186,259 adults with T2D, 56.7% (N = 105,533) did not fill a prescription for an AHA in the year after diagnosis and were included in the study. Of these 105,533 adults (mean age 59.6 years; 51.4% female), 75.0% were untreated for the entire 5 years post diagnosis. In the delayed treatment group, metformin was the most common first-line therapy (72.9%), and 83.0% of those who initiated monotherapy never received additional classes of AHAs. Compared to the delayed treatment group, the untreated group had significantly higher rates of incident cardiovascular outcomes and all-cause direct total costs ($118,191 vs $108,687; P < 0.05).

Conclusion: Over 50% of adults diagnosed with T2D were untreated with an AHA in the first year post diagnosis, and most of those who went untreated the first year remained untreated after 5 years. Among the delayed treatment patients, the majority did not use additional AHA classes besides their index therapy in the post-period. These findings suggest that therapeutic inertia affects a significant percentage of individuals with T2D. Given the untreated group's significantly worse cardiovascular outcomes and higher medical costs, these findings highlight a potential unmet need in the years immediately following T2D diagnosis.

Introduction: Many individuals in the community have undiagnosed glucose intolerance, type 2 diabetes (T2D), and pre-diabetes (Pre-DM). This study explored screening for unknown glucose intolerance in the emergency department (ED) in an acute hospital.

Methods: 1382 persons attending the ED without T2D were screened using HbA1c. T2D and Pre-DM were classified using American Diabetes Association (ADA) and National Institute for Health and Care Excellence (NICE) criteria. The Finnish Diabetes Risk Score (FINDRISC) was calculated in all patients.

Results: According to NICE criteria, 80.1% (1107 individuals) exhibited normal glucose tolerance, 11.6% (160 individuals) exhibited pre-diabetes, and 8.3% (115 individuals) exhibited diabetes. Each unit increase in FINDRISC score, using multinomial regression, corresponded to an 8% (5-12%; p < 0.001) higher risk for pre-diabetes and a 16% (10-23%; p < 0.001) higher risk for diabetes (NICE). The risk remained elevated even after adjusting for age, sex, and ethnicity. South-Asians had higher glucose intolerance rates than white British (34.8% versus 18.5%) using the NICE criteria, and even greater at 50.0% versus 37.6% using ADA criteria. The adjusted relative risk of having pre-diabetes in people of color compared with white British individuals was 1.77 (1.04-3.00; p = 0.034, ADA) and 2.84 (1.41-5.65; p = 0.003, NICE). The multinomial relative-risk ratio (RRRs) for having diabetes by ethnicity was 2.97 (1.73-5.08; p < 0.0001, ADA) and 2.80 (1.59-4.94; p < 0.0001, NICE).

Conclusions: Routine HbA1c screening in the ED, with FINDRISC scoring, successfully identifies individuals with diabetes and pre-diabetes. This approach could enable early intervention, particularly in groups at higher risk of glucose intolerance.

Trial registration: ClinicalTrials.gov identifier, NCT04653545.

Introduction: Novel therapies, including disease-modifying and cell replacement therapies, may preserve or replace beta cells in people with type 1 diabetes. This study sought to understand how people living with type 1 diabetes or caring for someone with type 1 diabetes perceive the benefits and risks of novel therapies.

Methods: Semistructured qualitative interviews were conducted with 26 participants in the United States: four adolescents and 12 adults with type 1 diabetes, and 10 caregivers of children with type 1 diabetes. A description of the benefits and risks of disease-modifying and cell replacement therapies, developed with a steering committee of patients and clinicians, was presented during interviews to facilitate discussion among people living with type 1 diabetes and caregivers. A qualitative directed content analysis was conducted.

Results: Participants reported that type 1 diabetes and insulin therapy regimens impacted many life areas, with some participants reporting diabetes burnout. Most participants expressed that they would have considered trying disease-modifying therapies, most frequently citing perceived benefits such as reduced insulin reliance and an extended post-diagnosis "honeymoon period" providing time to prepare for life with diabetes. Cancer risk was the most frequently reported risk of concern for disease-modifying therapies. All participants expressed willingness to consider cell replacement therapies, with insulin independence and restored pancreatic function perceived to offer greater normalcy and freedom from the constant demands of diabetes. Participants reported concerns about the use of immunosuppressants and the risks and drawbacks of the cell replacement surgical procedure.

Conclusions: Despite concerns about the risks and drawbacks of novel therapies, most participants reported that they would consider trying disease-modifying and cell replacement therapies. There is no substitute for consulting people living with or caring for someone with type 1 diabetes when considering new therapies with novel risks and benefits.

Introduction: Weight and diabetes stigma among healthcare professionals (HCPs) may negatively impact treatment decisions, patient outcomes, and physician-patient interactions. We assessed the relationship between weight stigma, diabetes stigma, perceptions of healthcare quality, and avoidance of healthcare among adults with type 2 diabetes (T2D).

Methods: This observational, online survey-based study included 857 US adults with T2D. The survey included perceptions of patient-centered care with questions from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey, perceptions of provider communication with questions from the Diabetes Attitudes, Wishes, and Needs (DAWN) study, de novo questions assessing participants' interactions with HCPs, perceived weight stigma and discrimination, and healthcare quality/avoidance delay questions. Mean scores were reported for patient-reported outcome measures: Modified Weight Bias Internalization Scale, Weight Self-Stigma Questionnaire, and Type 2 Diabetes Stigma Assessment Scale. Additional analyses were based on CAHPS, DAWN, and healthcare quality/avoidance responses.

Results: High degrees of weight bias internalization (WBI) and diabetes stigma were observed among participants dissatisfied with their HCP's overall involvement in their care and those who perceived judgment from the HCP because of their weight. Participants with high degrees of WBI and diabetes stigma were more likely to avoid seeking care, felt uncomfortable with body examinations, and rarely underwent regular health checkups. Those who had suboptimal interactions with their HCPs reported greater stigma.

Conclusions: Increasing awareness among HCPs regarding weight and diabetes stigma and promoting compassionate communication in healthcare interactions may help diminish these forms of stigma, thereby potentially improving health outcomes for people with T2D.

Despite advances in cardiovascular risk reduction in type 2 diabetes (T2D), a persistent gap remains compared to individuals without diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RA) have provided consistent cardiovascular benefits. With more cardiovascular protective agents available for diabetes management, their incremental effect may be nearing a ceiling. The SURPASS-CVOT trial innovatively compared the dual GIP/GLP-1RA tirzepatide with the selective GLP-1RA dulaglutide, demonstrating noninferiority for major adverse cardiovascular events (MACE; HR 0.92; 95.3% CI 0.83-1.01; p = 0.086) and suggesting a potential 28% MACE risk reduction versus an imputed placebo. However, superiority over dulaglutide was narrowly missed. Despite greater improvements in glycemia (0.8% greater HbA1c reduction) and weight (7% greater weight loss), tirzepatide appeared to confer limited incremental cardiovascular benefit, raising questions about mechanism saturation or trial design constraints. Exploratory analyses showed promising benefits on mortality and renal function but require cautious interpretation. The trial's active comparator/imputed placebo design reflects an evolving ethical and therapeutic landscape in diabetes care. Whether dual incretin receptor agonism can meaningfully exceed current cardioprotective thresholds remains uncertain. By now, we may need new paradigms to overcome what may turn out to be a therapeutic ceiling for cardiovascular protection in the T2D population.