Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes in the PIONEER REAL Netherlands Multicentre, Prospective, Observational Study.

INTRODUCTION: In this phase 4, multicentre, prospective, non-interventional PIONEER REAL Netherlands study, we assessed clinical outcomes associated with once-daily oral semaglutide use in real-world clinical practice in adults living with type 2 diabetes (T2D) naïve to injectable glucose-lowering medication. METHODS: Participants initiated on oral semaglutide were followed for 34-44 weeks. Change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS) was the primary endpoint; secondary endpoints included change in body weight (BW) from BL to EOS, the proportion of participants with HbA1c < 7.0% at EOS and the composite endpoints of HbA1c reduction ≥ 1.0%-points with BW reduction ≥ 3% or ≥ 5% at EOS. Treatment satisfaction was assessed using the Diabetes Treatment Satisfaction Questionnaire (DTSQ status/change). Safety was evaluated in all participants who initiated oral semaglutide treatment. RESULTS: Oral semaglutide was initiated in 187 participants; 94.1% completed the study and 78.6% remained on treatment at EOS. At BL, 54.0% of participants were male, mean age was 58.8 years, mean duration of T2D was 8.7 years and mean body mass index was 35.1 kg/m2; mean HbA1c was 8.6% and mean BW was 103.1 kg. Significant improvements from BL to EOS were observed for HbA1c and BW (estimated change [95% confidence interval]: - 1.16%-points [- 1.48 to - 0.85]; p < 0.0001, and - 5.84 kg [- 6.88 to - 4.80]; p < 0.0001, respectively). At EOS, 47.5% of participants had an HbA1c level < 7.0%; 41.8% and 35.5% of participants achieved composite endpoints of HbA1c reduction ≥ 1.0%-points plus BW reduction ≥ 3% or ≥ 5%, respectively. DTSQ status and change scores improved by 2.1 (p = 0.0003) and 10.8 points (p < 0.0001), respectively. Oral semaglutide was easy or very easy to consume for 81.5% of participants. Adverse events were mostly mild/moderate, with gastrointestinal disorders being the most common. CONCLUSION: In this real-world population, we reported clinically significant reductions in HbA1c and BW, improved treatment satisfaction and no new safety concerns. A graphical abstract is available with this article. CLINICAL TRIAL REGISTRATION: NCT04601740.

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.

Impact of chronic kidney disease on survival after amputation in individuals with diabetes.

OBJECTIVE: To identify factors that influence survival after diabetes-related amputations. RESEARCH DESIGN AND METHODS: We abstracted medical records of 1,043 hospitalized subjects with diabetes and a lower-extremity amputation from 1 January to 31 December 1993 in six metropolitan statistical areas in south Texas. We identified mortality in the 10-year period after amputation from death certificate data. Diabetes was verified using World Health Organization criteria. Amputations were identified by ICD-9-CM codes 84.11-84.18 and categorized as foot, below-knee amputation, and above-knee amputation and verified by reviewing medical records. We evaluated three levels of renal function: chronic kidney disease (CKD), hemodialysis, and no renal disease. We defined CKD based on a glomerular filtration rate<60 ml/min and hemodialysis from Current Procedural Terminology (CPT) codes (90921, 90925, 90935, and 90937). We used χ2 for trend and Cox regression analysis to evaluate risk factors for survival after amputation. RESULTS: Patients with CKD and dialysis had more below-knee amputations and above-knee amputations than patients with no renal disease (P<0.01). Survival was significantly higher in patients with no renal impairment (P<0.01). The Cox regression indicated a 290% increase in hazard for death for dialysis treatment (hazard ratio [HR] 3.9, 95% CI 3.07-5.0) and a 46% increase for CKD (HR 1.46, 95% CI 1.21-1.77). Subjects with an above-knee amputation had a 167% increase in hazard (HR 2.67, 95% CI 2.14-3.34), and below-knee amputation patients had a 67% increase in hazard for death. CONCLUSIONS: Survival after amputation is lower in diabetic patients with CKD, dialysis, and high-level amputations.

The value of debridement and Vacuum-Assisted Closure (V.A.C.) Therapy in diabetic foot ulcers.

BACKGROUND: Treatment of diabetic foot ulcers includes a number of different regimes such as glycaemic control, re-vascularization, surgical, local wound treatment, offloading and other non-surgical treatments. Although considered the standard of care, the scientific evidence behind the various debridements used is scarce. This presentation will focus on debridement and V.A.C. Therapy, two treatments widely used in patients with diabetes and foot ulcers. METHODS: A review of existing literature on these treatments in diabetic foot ulcers, with focus on description of the various types of debridements used, the principles behind negative pressure wound therapy (NPWT) using the V.A.C. Therapy system and level of evidence. RESULTS: Five randomized controlled trials (RCT) of debridement were identified; three assessed the effectiveness of a hydrogel as a debridement method, one evaluated surgical debridement and one evaluated larval therapy. Pooling the three hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers. Surgical debridement and larval therapy showed no significant benefit. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. More than 300 articles have been published on negative pressure wound therapy, including several small RCTs and a larger multi-centre RCT of diabetic foot ulcers. Negative pressure wound therapy seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care. CONCLUSIONS: Although debridement of the ulcer is considered a prerequisite for healing of diabetic foot ulcers, the grade of evidence is quite low. This may be due to a lack of studies rather than lack of effect. Negative pressure wound therapy seems to be safe and effective in the treatment of some diabetic foot ulcers, although there is still only one well-performed trial that evaluates the effect.

Amputations and ulceration; pitfalls in assessing incidence.

In order to direct scientific research, it is pivotal to know the extent of a clinical problem. Therefore, much effort has been undertaken to tally all diabetic foot problems around the world. Incidence and prevalence figures concerning both foot ulcerations and lower extremity amputations have been reported extensively worldwide. The figures presented are being compared with those from other countries, regions or clinics and those with the lowest numbers are deemed best practices.However, for these comparisons to be valid there are many possible pitfalls that are to be considered. A significant number of epidemiological and clinical considerations are to be dealt with and many of these are extremely important to realize when comparing ulceration or amputation rates. The influence of using a certain definition of nominators and denominators are explained. Also, the clinical setting in which the research has been performed is of importance. Many possible pitfalls are discussed in this presentation. Although there are limitations to this type of research, it may be the only way possible to go. In order to compare health strategies in certain areas of the world or to determine the importance of an intervention, incidence and prevalence figures certainly may prove a beneficial effect and therefore justify an intervention. Therefore, given the limitations epidemiological research concerning the prevalence and incidence of foot-related complications still forms the backbone of clinical research in the area of the diabetic foot.

2005: The International Diabetes Federation focuses on the diabetic foot.

The International Diabetes Federation (IDF) has proclaimed 2005 to be the "Year of the Diabetic Foot." Together with the International Working Group on the Diabetic Foot, the IDF has launched a year-long campaign to raise awareness of the diabetic foot worldwide. In this article, both organizations are briefly described, an overview of the aims of the global awareness campaign is given, and the activities to promote World Diabetes Day in 2005 are outlined. Attention is also paid to present and future developments to improve the standards of diabetic foot care worldwide.

Reduction in diabetes-related lower-extremity amputations in The Netherlands: 1991-2000.

OBJECTIVE: Lower-extremity amputation is a common complication among patients with diabetes throughout the world. However, few data exist on the actual impact of the recent moves to improve the management of diabetic foot ulcers to reduce the incidence of lower-extremity amputations. The aim was to determine the incidence of lower-extremity amputations among diabetic patients from 1991 to 2000 in The Netherlands. RESEARCH DESIGN AND METHODS: A secondary database containing information regarding all hospital admissions in which a lower-extremity amputation occurred for the years 1991-2000 was obtained from the Dutch National Medical Register. Because a patient-unique identifier was included, multiple amputations and hospitalizations for a single individual could be identified. Furthermore, age- and sex-specific diabetes prevalence rates were calculated using a 3-year average for every year, calculating the total diabetic population in the Netherlands at risk for every year. RESULTS: In 1991, a total of 1,687 patients with diabetes had been admitted 1,865 times for 2,409 amputations. In 2000, a total of 1,673 patients with diabetes were admitted 1,932 times for 2,448 amputations. The overall incidence rates of the number of patients who underwent lower-extremity amputation decreased over the years from 55.0 to 36.3 per 10,000 patients with diabetes (P < 0.05). Both in men (71.8 vs. 46.1, P < 0.05) and women (45.0 vs. 28.0, P < 0.05) with diabetes, a significant decrease could be observed. Mean duration of hospitalization decreased from 45.0 days (SD 44.4) in 1991 to 36.2 days (SD 38.4) in 2000; decreases were observed for both men and women. CONCLUSIONS: Over the years observed in this study, the incidence rates of diabetes-related lower-extremity amputation in The Netherlands was found to decrease in both men (36%) and women (38%) with diabetes. Furthermore, the duration of hospitalization decreased over time.