LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial

Background: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results—A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. Methods: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). Results: Mean BMI was 32.5 ± 6.3 kg/m2 and only 9.1 % had BMI <25 kg/m2. The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. Conclusions: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints

LEADER-6: Baseline renal function and associated factors in a high cardiovascular risk type 2 diabetes population

Aims: To examine the prevalence of chronic kidney disease (CKD) and its associated factors in a multinational population with type 2 diabetes mellitus (T2DM) and prior cardiovascular disease (CVD)

Initiation of once daily insulin detemir is not associated with weight gain in patients with type 2 diabetes mellitus: results from an observational study

Background: Obesity is common in type 2 diabetes (T2DM) and is associated with increased risk of morbidity and all-cause mortality. This analysis describes weight changes associated with insulin detemir initiation in real-life clinical practice. Methods: Study of Once-Daily Levemir (SOLVE) was a 24-week international observational study of once-daily insulin detemir as add-on therapy in patients with T2DM receiving oral hypoglycaemic agents (OHAs). Results: 17,374 participants were included in the analysis: mean age 62 ± 12 years; weight 80.8 ± 17.6 kg; body mass index (BMI) 29.2 ± 5.3 kg/m2; diabetes duration 10 ± 7 years; HbA1c 8.9 ± 1.6%. HbA1c decreased by 1.3 ± 1.5% during the study, with insulin doses of 0.27 ± 0.17 IU/kg. Patients with higher BMI had higher pre-insulin HbA1c, and similar reductions in HbA1c with insulin therapy. Weight decreased from 80.8 ± 17.6 kg to 80.3 ± 17.0 kg (change of -0.6 [95% CI -0.65; -0.47] kg), with 35% of patients losing >1 kg. Patients with the highest pre-insulin BMI lost the greatest amount of weight: BMI < 25: +0.8 [95% CI: 0.6; 0.9] kg, 25 ≤ BMI < 30: -0.2 [95% CI: -0.3; -0.8] kg, 30 ≤ BMI < 35: -1.0 [95% CI: -1.1; -0.8] kg; BMI ≥ 35: -1.9 [95% CI: -2.2; -1.6] kg. Minor hypoglycaemia decreased with increasing BMI: 2.3 and 1.3 events per patient year for BMI <25 and  ≥ 35, respectively. Conclusions: Overall, patients with poorly controlled T2DM achieved significant reductions in HbA1c after initiation of once-daily insulin detemir therapy, without weight gain. The favourable impact of insulin detemir on weight may not apply to other insulin preparations

LEADER 5: prevalence and cardiometabolic impact of obesity in cardiovascular high-risk patients with type 2 diabetes mellitus: baseline global data from the LEADER trial

BACKGROUND: Epidemiological data on obesity are needed, particularly in patients with type 2 diabetes mellitus (T2DM) and high cardiovascular (CV) risk. We used the baseline data of liraglutide effect and action in diabetes: evaluation of CV outcome results-A long term Evaluation (LEADER) (a clinical trial to assess the CV safety of liraglutide) to investigate: (i) prevalence of overweight and obesity; (ii) relationship of the major cardiometabolic risk factors with anthropometric measures of adiposity [body mass index (BMI) and waist circumference (WC)]; and (iii) cardiometabolic treatment intensity in relation to BMI and WC. METHODS: LEADER enrolled two distinct populations of high-risk patients with T2DM in 32 countries: (1) aged ≥50 years with prior CV disease; (2) aged ≥60 years with one or more CV risk factors. Associations of metabolic variables, demographic variables and treatment intensity with anthropometric measurements (BMI and WC) were explored using regression models (ClinicalTrials.gov identifier: NCT01179048). RESULTS: Mean BMI was 32.5 ± 6.3 kg/m(2) and only 9.1 % had BMI <25 kg/m(2). The prevalence of healthy WC was also extremely low (6.4 % according to International Joint Interim Statement for the Harmonization of the Metabolic Syndrome criteria). Obesity was associated with being younger, female, previous smoker, Caucasian, American, with shorter diabetes duration, uncontrolled blood pressure (BP), antihypertensive agents, insulin plus oral antihyperglycaemic treatment, higher levels of triglycerides and lower levels of high-density lipoprotein cholesterol. CONCLUSIONS: Overweight and obesity are prevalent in high CV risk patients with T2DM. BMI and WC are related to the major cardiometabolic risk factors. Furthermore, treatment intensity, such as insulin, statins or oral antihypertensive drugs, is higher in those who are overweight or obese; while BP and lipid control in these patients are remarkably suboptimal. LEADER confers a unique opportunity to explore the longitudinal effect of weight on CV risk factors and hard endpoints

Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.

BACKGROUND: Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown. METHODS: We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m RESULTS: Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m CONCLUSIONS: Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.)

The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a common complication of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and lower body weight in people with T2D, and some reduce risk of cardiovascular (CV) events in those with high CV risk. GLP-1RAs might also have kidney-protective effects. We report the design and baseline data for FLOW, a trial investigating the effects of once-weekly (OW) GLP-1RA semaglutide on kidney outcomes in participants with CKD and T2D. METHODS: FLOW is a randomised, double-blind, parallel-group, multinational, phase 3b trial. Participants with T2D, estimated glomerular filtration rate (eGFR) ≥50‒≤75 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) \u3e300‒100‒ RESULTS: Enrolled participants (N = 3 534) had a baseline mean (SD) age of 66.6 (9.0) years, HbA1c of 7.8 (1.3) %, diabetes duration of 17.4 (9.3) years, eGFR of 47.0 (15.2) mL/min/1.73 m2 and median UACR of 568 (range: 2‒11 852) mg/g. According to Kidney Disease: Improving Global Outcomes guideline categorisation, 68.2% were at very high risk for CKD progression. CONCLUSION: FLOW will evaluate the effect of semaglutide on kidney outcomes in participants with CKD and T2D, and is expected to complete in late 2024

Genetic factors affect the etiology, clinical characteristics and outcome of autoimmune hepatitis

Autoimmune hepatitis (AIH) is characterized by chronic inflammation of the liver, hypergammaglobulinemia, the presence of serum autoantibodies, histologic evidence of interface hepatitis, and a favorable response to immunosuppressive treatment. Although the etiology of AIH remains undefined, human leukocyte antigen (HLA) class II alleles have been associated with disease onset for decades. AIH resistance and severity are presumably linked to HLA alleles as well. Individuals in different geographic regions of the world may have varying susceptibility alleles that reflect indigenous triggering antigens. In this review, we describe the influence of HLA alleles and gene polymorphisms on AIH, along with the results of genome-wide association studies on this disease