Once-weekly semaglutide use in patients with type 2 diabetes: Results from the SURE France multicentre, prospective, observational study.

AIMS: Real-world data are required to support glucagon-like peptide-1 receptor agonist use in type 2 diabetes (T2D). SURE France assessed once-weekly semaglutide in adults with T2D in real-world clinical practice. MATERIALS AND METHODS: This multicentre, prospective, open-label, single-arm study included adults with T2D and ≥1 documented glycated haemoglobin (HbA1c) value ≤12 weeks before semaglutide initiation. The primary endpoint was HbA1c change from baseline to end of study (EOS; ~30 weeks). Secondary endpoints included change from baseline to EOS in body weight (BW) and waist circumference (WC); and proportion achieving HbA1c targets. Baseline characteristics and safety were reported for the full analysis set (patients initiating semaglutide). Analysis of other endpoints was based on the effectiveness analysis set (study completers receiving semaglutide at EOS). RESULTS: Of 497 patients initiating semaglutide (41.6% female, mean age 58.3 years), 348 completed the study on treatment. Baseline HbA1c, diabetes duration, BW and WC, were 8.3%, 10.0 years, 98.2 kg and 114.2 cm, respectively. The most common reasons for initiating semaglutide were to improve glycaemic control (79.7%), reduce BW (69.8%) and address cardiovascular risk (24.1%). At EOS, mean changes were: HbA1c, -1.2% points [95% confidence interval (CI) -1.32; -1.10]; BW, -4.7 kg (95% CI -5.38; -4.07); and WC, -4.9 cm (95% CI -5.94; -3.88). At EOS, 81.7%, 67.7% and 51.6% of patients achieved an HbA1c target of <8.0%, <7.5% and <7.0%, respectively. No new safety concerns were identified. CONCLUSIONS: These results support the benefits of semaglutide in a real-world setting in adults with T2D in France showing a significant reduction in HbA1c and body weight.

Glycosuria amount in response to hyperglycaemia and risk for diabetic kidney disease and related events in Type 1 diabetic patients.

BACKGROUND: Hyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes. METHODS: During the period 1990-92, we studied the tubulo-glomerular feedback in Type 1 diabetic patients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR <60 mL/min/1.73 m2, doubling of serum creatinine, end-stage renal disease or all-cause death. RESULTS: Glycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P < 0.05). Over 21 years, 31.5% high- versus 12.7% low-risk patients developed endpoints (adjusted P = 0.006). In a multi-adjusted survival analysis of patients having undergone renal tests, each 0.10 mmol/min glycosuria during hyperglycaemia reduced the outcome risk by 0.72 (95% confidence interval 0.49-0.97, P = 0.03). CONCLUSIONS: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.

Lower-extremity amputation as a marker for renal and cardiovascular events and mortality in patients with long standing type 1 diabetes.

BACKGROUND: We evaluated the risks of renal and cardiovascular complications, and mortality associated with lower extremity amputation (LEA) in patients with type 1 diabetes. METHODS: We studied two cohorts of people with long standing type 1 diabetes: GENEDIAB (n = 456) and GENESIS (n = 611). Subsets of the cohorts (n = 260, n = 544) were followed for 9 and 5 years, respectively. Outcomes were the incidence of end stage renal disease (ESRD), myocardial infarction, stroke and mortality during follow-up. Analyses were performed in pooled cohorts. RESULTS: The prevalence of LEA at baseline was 9.3 % (n = 99). A positive history of LEA was associated with the baseline prevalence of established (OR 4.50, 95 % CI 2.33-8.91, p < 0.0001) and advanced diabetic nephropathy (OR 5.50, 95 % CI 2.89-10.78, p < 0.0001), ESRD (OR 2.86, 95 % CI 1.43-5.50, p = 0.004), myocardial infarction (OR 3.25, 95 % CI 1.68-6.15, p = 0.0006) and stroke (OR 3.88, 95 % CI 1.67-8.72, p = 0.002, adjusted for sex, age, and cohort membership). A positive history of LEA at baseline was associated with the incidence during follow-up of ESRD (HR 2.69, 95 % CI 1.17-6.20, p = 0.02), and myocardial infarction (HR 3.53, 95 % CI 1.79-6.97, p = 0.0001). History of LEA was also associated with increased risk for all-cause (HR 3.55, 95 % CI 2.05-6.16, p < 0.0001), cardiovascular (HR 3.30, 95 % CI 1.36-8.02, p = 0.008), infectious disease (HR 5.18, 95 % CI 1.13-23.84, p = 0.03) and other-cause mortality (HR 2.81, 95 % CI 1.09-7.26, p = 0.03). History of LEA at baseline was associated with a 40 % reduction in the duration of survival in the subset of patients who died during follow-up. Population attributable risk of the history of LEA at baseline for total mortality during follow-up was 0.31. CONCLUSIONS: Patients with LEA have a higher risk of ESRD, myocardial infarction and cardiovascular and non-cardiovascular mortality. Our results highlight the importance of LEA as a key-predictor for major vascular events and premature death in type 1 diabetic patients.

Comparison of a new versus standard removable offloading device in patients with neuropathic diabetic foot ulcers: a French national, multicentre, open-label randomized, controlled trial.

INTRODUCTION: The offloading is crucial to heal neuropathic diabetic foot ulcer (DFU). Removable offloading are the most used devices. Orthèse diabète is a new customized removable knee-high offloading device immobilizing foot and ankle joints, with some specific and innovative features that may improve offloading. We aimed to evaluate the efficiency of this device in DFU healing. RESEARCH, DESIGN AND METHODS: The evaluation of Offloading using a new removable ORTHOsis in DIABetic foot study is a French multicenter (13 centers) randomized controlled trial with blinded end points evaluation. Adults with neuropathic DFU were randomly assigned to either Orthèse Diabète (experimental device), or any type of conventional (usually used in France) removable offloading devices (control group). The primary outcome was the 3-month proportion of patients with fully healed DFU. RESULTS: Among 112 randomized patients (men 78%, age 62±10 years), the primary outcome occurred in 19 (33%) participants using conventional device vs 19 (35%) Orthèse Diabète users (p=0.79). Study groups were also comparable in terms of prespecified secondary end points including occurrence of new DFU (25% vs 27% in conventional and experimental groups), ipsilateral lower-limb amputation (4% vs 10%) or infectious complications (14% vs 13%) (p>0.05 for all). Adverse events were comparable between groups, including 4 deaths unrelated to study allocation (1 sudden death, 2 ventricular arrhythmias and 1 pancreatic cancer). Adverse events believed to be related to the device were higher in the Orthèse Diabète group than in the control group (15% vs 4%). Orthèse Diabète was less frequently worn than conventional devices (46% vs 66%, p=0.04). CONCLUSIONS: Orthèse Diabète, a new removable offloading orthosis immobilizing foot and ankle joints did not show superiority compared with conventional removable devices in neuropathic DFU healing and cannot be recommended to heal DFU. TRIAL REGISTRATION NUMBER: NCT01956162.

Outpatient measurement of arterial stiffness in patients with type 2 diabetes and obesity.

BACKGROUND: Pulse wave velocity (PWV) is a marker of arterial stiffness. The aim of the present study was to compare PWV in patients with type 2 diabetes mellitus (T2DM) or obesity and healthy subjects in an outpatient setting. METHODS: A cross-sectional study was conducted in patients with obesity without T2DM (n = 37), T2DM without obesity (n = 40), T2DM plus obesity (n = 43), and healthy controls (n = 114). Outpatient measurements of the finger-toe PWV (ftPWV) were made. RESULTS: Mean (± SD) ftPWV was higher in men than in women (10.57 ± 5.02 vs 9.14 ± 3.68 m/s, respectively P = 0.006) and was positively correlated with age (r2 = 0.31, P < 0.0001), body mass index (r2 = 0.03, P = 0.01), systolic blood pressure (SBP; r2 = 0.06, P < 0.0001), and right (r2 = 0.03, P = 0.01) and left (r2 = 0.03, P = 0.01) ankle-brachial index (ABI). Age, SBP and ABI remained significantly correlated with ftPWV in the stepwise regression analysis. Mean ftPWV in controls and in patients with obesity, T2DM, and T2DM plus obesity was 8.32 ± 2.68, 9.50 ± 3.38, 11.29 ± 4.34, and 12.36 ± 6.67 m/s, respectively (P < 0.0001). These differences remained significant after adjustments for sex, age, SBP, and ABI (P = 0.008). Although ftPWV was higher in patients with than without macrovascular complications (13.11 ± 6.25 vs 10.40 ± 4.54 m/s, respectively; P = 0.006) in univariate analysis, this was not so in the multivariate-adjusted model. CONCLUSIONS: Outpatient-measured ftPWV was correlated with age, SBP, and ABI. It was higher in patients with T2DM and obesity compared with healthy controls. The highest ftPWV was observed in patients with both T2DM and obesity.

Impact of morbid obesity on the kidney function of patients with type 2 diabetes.

AIMS: Type 2 diabetes and obesity impair kidney function. We examined their respective contributions to urinary albumin excretion (UAE) and glomerular filtration rate (GFR) in patients with type 2 diabetes and morbid obesity. METHODS: Cross-sectional, monocentric study of kidney function in patients with type 2 diabetes classified into four body mass index (BMI) stages: non-obese (<25 kg/m(2), n=157); overweight (25 to <30, n=311); obesity (30 to <40, n=310); and morbid obesity (≥40, n=77), with 84 similarly staged controls without diabetes. UAE classes were defined as normal (<30 µg/mg creatinine), microalbuminuria (30-299), or macroalbuminuria (≥300) from 3 consecutive urine samples. GFR was measured by (51)Cr EDTA plasma disappearance (adjusted and unadjusted to 1.73 m(2) body surface area, as obesity increases body surface). RESULTS: Participants with type 2 diabetes had same age, diabetes duration, and HbA1c across BMI stages. UAE was higher in participants with type 2 diabetes (p<0.0001), and increased with obesity stages (p<0.0001). After adjustment for age, sex, systolic blood pressure and type 2 diabetes status, morbid obesity was associated with a risk of microalbuminuria (OR 1.99, 95%CI 1.35-2.98, p=0.0007) and macroalbuminuria (OR 2.33, 95%CI 1.25-4.22, p=0.006). The body surface adjusted GFR was lower in patients with type 2 diabetes than in controls (p<0.0001), and declined with obesity stages, contrary to controls. An interaction of diabetes and obesity was seen with unadjusted GFR values (p=0.002). CONCLUSIONS: Morbid obesity interacts with type 2 diabetes to aggravate UAE and GFR. Treatment strategies should focus on both conditions to protect kidney function in these patients.