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.

The health and budget impact of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in The Netherlands.

OBJECTIVES: Type-2 Diabetes mellitus (T2DM) increases both the patient risk of cardiovascular disease (CVD) and renal outcomes, such as chronic kidney disease (CKD). Recent clinical trials of the glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown benefits in preventing CVD events and progression of CKD, leading to an update of the Dutch T2DM treatment guideline for patients at risk. The aim of this study is to assess the health and economic impact of the guideline-recommended utilization of SGLT2is in the Netherlands. METHODS: The patient population at risk was determined by multiplying Dutch T2DM prevalence rates with the total numbers of inhabitants of the Netherlands in 2020. Subsequently, two analyses, comparing a treatment setting before and after implementation of the new guideline for SGLT2is, were conducted. Clinical and adverse event rates in both settings as well as direct healthcare costs were sourced from the literature. Total costs were calculated by multiplying disease prevalence, event rates and costs associated to outcomes. One-time disutilities per event were included to estimate the health impact. The potential health and economic impact of implementing the updated guideline was calculated. RESULTS: Using a 5-year time horizon, the guideline-suggested utilization of SGLT2is resulted in a health impact equal to 4835 quality adjusted life years gained (0.0031 per patient per year) and €461 million cost-savings. The costs of treatment with SGLT2is were €813 million. Hence the net budget impact was €352 million for the total Dutch T2DM population, which translated to €0,57 per patient per day. CONCLUSION: SGLT2is offer an option to reduce the number of CVD and CKD related events and associated healthcare costs and health losses in the Netherlands. Further research is needed to include the benefits of improved T2DM management options from a broader societal perspective.HighlightsThe glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) has shown benefits in preventing cardiovascular events and progression of kidney disease in patients with type-2 diabetes leading to a revision of the respective Dutch treatment guideline.The 5-year budget impact of the adoption of SGLT2is in the new treatment guideline was equal to €352 million or €0.57 per patient per day, with a total of 4385 quality adjusted life years gained.The introduction of SGLT2is for Dutch type-2 diabetes patients has the potential to substantially reduce the number of cardiovascular as well as renal disease events and related healthcare costs while also delivering a health benefit.

Impairments as measured by ISS do not greatly change between one and eight years after CRPS 1 diagnosis.

BACKGROUND: Complex Regional Pain Syndrome type 1 (CRPS 1) is a potentially incapacitating complication in which pain seems to be the most disabling factor. We performed a late follow up study of a well-defined CRPS 1 population more than eight years after diagnosis. The relationships between early and late impairments were studied with a view to outcome prediction and to investigate possible differences in long-term impairments according to initial CRPS 1 subdiagnosis (i.e. "warm" or "cold", diagnosed according to skin temperature measured via infrared thermometer). METHODS: We again measured patients using the Impairment Level SumScore (ISS) (T8). These data were compared with earlier ISS measurements at CRPS diagnosis (T0) and after one year's treatment (T1). Correlations were determined between these measures. RESULTS: Forty-five patients participated in the present study. Total median ISS improved by 55% (statistically/clinically significant) after one year's treatment (T1), and worsened (non-significantly) by 14% from T1 to T8 - without differences according to original subdiagnosis. ISS correlations were stronger for T1 vs. T8 than for T0 vs. T1 or T0 vs. T8, being strongest for the ISS factors related to pain. CONCLUSIONS: Considerable impairments, as measured by ISS, are still present over eight years after first CRPS 1 diagnosis. These do not greatly change between one and eight years post-diagnosis. ISS outcomes are similar for "cold" and "warm" CRPS 1 diagnostic subgroups. Component ISS scores associated with pain appear to possess greatest predictive power.

Patients initially diagnosed as 'warm' or 'cold' CRPS 1 show differences in central sensory processing some eight years after diagnosis: a quantitative sensory testing study.

We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.