Clinical Recommendations to Manage Gastrointestinal Adverse Events in Patients Treated with Glp-1 Receptor Agonists: A Multidisciplinary Expert Consensus

Gastrointestinal adverse events; Obesity; Type 2 diabetesEsdeveniments adversos gastrointestinals; Obesitat; Diabetis tipus 2Eventos adversos gastrointestinales; Obesidad; Diabetes tipo 2Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are indicated in type 2 diabetes and obesity for their high efficacy in controlling glycaemia and inducing body weight loss, respectively. Patients may develop gastrointestinal adverse events (GI AEs), namely nausea, vomiting, diarrhoea and/or constipation. To minimize their severity and duration, healthcare providers (HCPs) and patients must be aware of appropriate measures to follow while undergoing treatment. An expert panel comprising endocrinologists, nephrologists, primary care physicians, cardiologists, internists and diabetes nurse educators convened across virtual meetings to reach a consensus regarding these compelling recommendations. Firstly, specific guidelines are provided about how to reach the maintenance dose and how to proceed if GI AEs develop during dose-escalation. Secondly, specific directions are set about how to avoid/minimize nausea, vomiting, diarrhoea and constipation symptoms. Clinical scenarios representing common situations in daily practice, and infographics useful to guide both HCPs and patients, are included. These recommendations may prevent people with T2D and/or obesity from withdrawing from GLP-1 RAs treatment, thus benefitting from their superior effect on glycaemic control and weight loss.This work has been funded by Novo-Nordisk

Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study

Objectives: Scientific literature about the combination of glucagon-like peptide-1 receptor agonists (GLP1ra) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients is scarce. We sought to assess the real-world efficacy and safety of SGLT2 inhibitors and GLP-1ra combination therapy in older patients (>65 years of age). Methods: This was an observational, prospective, multicenter study based on clinical practice. Patients were stratified according to tertiles of baseline glycated hemoglobin (A1C) levels and to treatment schedule. Results: We included 113 patients (65.5% men, mean age 70.4±8.8 years). The body mass index was 36.5 (±6.6) kg/m2. The baseline A1C level was 8.0% (±1.2%). At the 6-month follow up, we found a significant reduction in A1C levels (–1.1%; p<0.0001), body mass index (–2.1 kg/m2; p<0.00003) and systolic blood pressure (–13 mmHg; p<0.000005). Patients who had the highest baseline A1C levels (≥8.4%) showed greater improvement in A1C levels (p<0.0001), weight (p<0.0001) and quality-of-life scores (p<0.0001). The greatest reduction in A1C levels and weight was seen in patients who started both drugs simultaneously (p<0.0001). The second greatest reduction was seen when GLP-1ra was added to previous treatment with an SGLT2i (p<0.0001). Also of note was a decrease in systolic blood pressure in patients for whom an SGLT2i was added to previous GLP-1ra treatment (p<0.0001). Of the patients, 34.3% achieved the combined endpoint of A1C levels <7% and weight loss ≥5% without hypoglycemia. Conclusions: This study’s findings provide evidence of clinically meaningful reductions in A1C level, body weight and systolic blood pressure in older patients with type 2 diabetes who are taking combined regimens. The dropout and hypoglycemia rates were minimal, and treatment was tolerated well

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Aims: We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to prevent worsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. Methods: A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. Results: All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2 , respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50-22.4) (-24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54-296.5 mg/g; P < .001. Patients with urinary albumin-to-creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5-104.99]) (-56 ± 65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. Conclusion: Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control

¿Son todos los efectos adversos en el tratamiento de la diabetes realmente indeseables?

No aplicabl

Serum uric acid levels and outcome during admission in acute ischaemic stroke, depending on renal function

<p><b>Background:</b> The relationship between serum uric acid (SUA) levels and stroke is controversial. The discrepancies in the results could be due to the uneven setting of comorbidity. It is known that hyperuricaemia increases in parallel with the decline in renal function; however, there are few studies that adjust for renal disease.</p> <p><b>Aim:</b> To investigate the relationship between SUA levels in the acute phase of ischaemic stroke according to the presence or absence of chronic kidney disease and clinical outcomes during admission.</p> <p><b>Methods:</b> Retrospective cross-sectional analysis of patients recruited through a unicentric stroke registry. The sample was divided according to its quartiles of SUA. Renal disease was defined based on the haematocrit, urea and Gender (HUGE) formula. The outcome was determined by the National Institutes of Health Stroke Scale (NIHSS) score. Statistically robust methods were used with R (version 3.3.2).</p> <p><b>Results:</b> A total of 412 patients (53.8% male) were analysed. The NIHSS score decreased as the SUA levels increased (<i>p</i> < 0.0009). Robust linear regression analysis showed a significant association between quantitative SUA levels and NIHSS score (<i>p</i> < 0.0003), even when patients were categorized according to renal function (<i>p</i> < 0.05). In an adjusted multivariate model, SUA levels showed an independent protective effect on the severity of stroke (OR = 0.67, 95% CI 0.51–0.88, <i>p</i> = 0.004).</p> <p><b>Conclusions:</b> Our results support the hypothesis that hyperuricaemia plays a protective role in the prognosis of stroke, independently from renal function, and that even in patients with chronic kidney disease, it remains as a protective agent.</p

Hyponatremia as predictor of worse outcome in real world patients admitted with acute heart failure

Background: Our aim was to determine if hyponatremia, defined as serum sodium level &lt; 135 mmol/L, is a predictor of worse outcome in a cohort of real-world patients with heartfailure (HF).Methods: We used data of the National registry of HF (RICA) from Spain, an ongoing multicenter, prospective cohort study. The patients were assigned to two groups regarding sodium levels. Primary end-point was first all-cause readmission, or death by any cause. Secondary end-points were the number of days hospitalized, and the presence of complications.Results: We identified 973 patients, 147 (15.11%) with hyponatremia. The median age of patients enrolled was 77.25 ± 8.79 years-old, the global comorbidity measured by Charlson comorbidity index (CCI) was upper 3 points and preserved ejection fraction was present in67.1% of them. Clinical complications during admission were significantly higher in the patients with hyponatremia (35.41%, p &lt; 0.001) and this remained as significant predictor after logistic regression adjustment (OR 1.08, p &lt; 0.01). Also mortality and readmissions were more frequent in patients with hyponatremia (20.69% and 22.41%, respectively) but after Cox regression adjustment hyponatremia in our cohort was not associated with increase in 90-day all-cause mortality and readmissions, and only CCI remained significant for primaryend-point (HR 1.08, p &lt; 0.001).Conclusions: Hyponatremia is an independent predictor of complications during hospitalization in our real-world cohort, but was not associated with 90 days mortality or readmissions. Global comorbidity, however, played an important role, and could influence the mortality and readmissions of our patients