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IntroductionVERTIS CV is the cardiovascular outcome trial for the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin. A sub-study was conducted to assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately glycemic-controlled on metformin and a sulfonylurea (SU).MethodsPatients with T2DM, established atherosclerotic cardiovascular disease (ASCVD), and an HbA1c of 7.0-10.5% on stable metformin (≥ 1500 mg/day) and moderate to high SU doses were randomly assigned to once-daily ertugliflozin (5 or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ertugliflozin on HbA1c compared with placebo and to evaluate safety following 18 weeks of treatment. Key secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), blood pressure (BP), and the proportion of patients achieving HbA1c

The article discusses a study that examined the relationship between hypoglycemia and kidney events in individuals with type 2 diabetes and cardiovascular disease. The study found no significant association between hypoglycemia events and adverse kidney outcomes. However, it did find that a previous adverse kidney outcome was linked to a higher risk of subsequent hypoglycemia events. The authors recommend further research using real-world data to explore this association and the safety of glucose-lowering medications. [Extracted from the article]

This article discusses the results of a post-hoc analysis of the VERTIS CV trial, which examined the effects of the medication ertugliflozin on the risk of hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease. The study found that ertugliflozin significantly reduced the risk of first HHF in the overall cohort of participants. However, the treatment effect was more pronounced in individuals with a pre-trial ejection fraction (EF) of less than 45% and attenuated in those with an EF greater than 60%. These findings contribute to the understanding of the efficacy of SGLT2 inhibitors in reducing the risk of HHF across different EF ranges. [Extracted from the article]

Aim: To conduct a post hoc analysis to explore indices of hepatic steatosis/fibrosis and cardiorenal outcomes in the VERTIS CV study. Materials and Methods: Patients with type 2 diabetes and atherosclerotic cardiovascular (CV) disease were randomized to ertugliflozin or placebo. Liver steatosis and fibrosis were assessed post hoc using the hepatic steatosis index (HSI) and fibrosis‐4 (FIB‐4) index to explore associations with cardiorenal outcomes (ertugliflozin and placebo data pooled, intention‐to‐treat analysis set). Cardiorenal outcomes (major adverse CV events [MACE]; hospitalization for heart failure [HHF]/CV death; CV death; HHF; and a composite kidney outcome) were stratified by baseline HSI and FIB‐4 quartiles (Q1‐Q4). Change in liver indices and enzymes over time were assessed (for ertugliflozin vs. placebo). Results: Amongst 8246 participants, the mean age was 64.4 years, body mass index 32.0 kg/m2, HSI 44.0 and FIB‐4 score 1.34. The hazard ratios (HRs) for MACE, HHF/CV death, CV death, and HHF by FIB‐4 score quartile (Q4 vs. Q1) were 1.48 (95% confidence interval [CI] 1.25, 1.76), 2.0 (95% CI 1.63, 2.51), 1.85 (95% CI 1.45, 2.36), and 2.94 (95% CI 1.98, 4.37), respectively (P < 0.0001 for all). With HSI, the incidence of HHF was higher in Q4 versus Q1 (HR 1.52 [95% CI 1.07, 2.17]; P < 0.05). The kidney composite outcome did not differ across FIB‐4 or HSI quartiles. Liver enzymes and HSI decreased over time with ertugliflozin. Conclusion: In VERTIS CV, higher FIB‐4 score was associated with CV events. HSI correlated with HHF. Neither measure was associated with the composite kidney outcome. Ertugliflozin was associated with a reduction in liver enzymes and HSI. [ABSTRACT FROM AUTHOR]

Introduction: Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) "dip" with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. Methods: Patients were categorized into tertiles based on change in eGFR at week 6: >+1.00 mL/min/1.73 m2 (tertile 1), >−5.99 and ≤+1.00 (tertile 2), and ≤−6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline–week 6) and chronic periods (week 6–30 days after last dose of trial medication). Results: In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m2/year; weeks 6–156) were −0.76 (−1.03, −0.50), −0.29 (−0.51, −0.07), and −0.05 (−0.26, 0.17) in tertiles 1, 2, and 3, respectively (p value <0.001), and approximately −1.5 mL/min/1.73 m2/year across tertiles in the placebo group (p value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were −0.77, −0.71, and −0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All pinteraction values were <0.0001 for glucosuria- and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo- and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo- and ertugliflozin-treated groups. Conclusion: With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria- and natriuresis-related measures. [ABSTRACT FROM AUTHOR]

Aims: This prespecified exploratory analyses from VERTIS CV (NCT01986881) aimed to assess the effects of the sodium‐glucose cotransporter‐2 (SGLT2) inhibitor ertugliflozin on glucosuria‐related (glycated haemoglobin [HbA1c], uric acid, body weight) and natriuresis‐related (blood pressure, haemoglobin, haematocrit, serum albumin) biomarkers according to kidney function risk category. Materials and methods: Patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg (1:1:1). Analyses compared placebo (n = 2747) versus ertugliflozin (pooled; n = 5499) on glucosuria‐ and natriuresis‐related biomarkers according to baseline estimated glomerular filtration rate (eGFR) subgroup and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) risk category. Results: Patients were classified according to KDIGO CKD low‐ (49%), moderate‐ (32%) and high‐/very‐high‐risk categories (19%), and eGFR groups 1 (25%), 2 (53%) and 3 (19%). At Week 18, the high‐/very‐high‐risk category had a smaller placebo‐subtracted least squares mean (LSM) change from baseline (95% confidence interval) in HbA1c (−0.34 [−0.43, −0.25]) compared with the low‐ and moderate‐risk categories (−0.54 [−0.60, −0.49] and − 0.47 [−0.54, −0.40], respectively). This pattern was maintained throughout the study (Pinteraction = 0.0001). Similar patterns based on baseline eGFR G stage were observed. Placebo‐subtracted LSM changes from baseline in uric acid were lowest in the high‐/very‐high‐risk category at Weeks 6 and 18, but the pattern was not maintained after Week 156 (Pinteraction = 0.15). Effects of ertugliflozin on body weight and natriuresis‐related biomarkers did not differ across KDIGO CKD categories. Conclusions: In VERTIS CV, ertugliflozin was associated with physiologically favourable changes in glucosuria‐ and natriuresis‐related biomarkers. Glycaemic efficacy of ertugliflozin was attenuated in patients with higher chronic kidney disease (CKD) risk. Effects on other biomarkers were consistent, regardless of CKD risk stage. [ABSTRACT FROM AUTHOR]

Anorexia is a major complication of inflammatory bowel disease (IBD). We postulated that chronic intestinal inflammation with increased proinflammatory cytokines elevates serum leptin concentration, thereby contributing to anorexia. This hypothesis was studied in interleukin-2--deficient (IL-[2.sup.-/-]) mice, a model of IBD with elevated proinflammatory cytokine production. IL-[2.sup.-/-], wild-type pair-fed and wild-type control male mice (8 wk old) were fed regular laboratory mouse food for 2 wk. The IL-[2.sup.-/-] and pair-fed groups consumed less food and lost weight. Serum leptin concentrations in the IL-[2.sup.-/-] mice in the fed state were lower than controls, but not different from pair-fed mice, and paradoxically increased in the starved state to levels significantly higher than both starved control and pair-fed groups; This result did not change when serum leptin was adjusted for amount of body fat. These data show abnormal leptin responses in IL-[2.sup.-/-] mice with increased leptin concentrations disproportionate to fat mass and prevention of the normal decline in leptin with food restriction. J. Nutr. 132: 893-896, 2002. KEY WORDS: * leptin * IL-2--deficient mice * inflammatory bowel disease * inflammation

The functions of melanin-concentrating hormone (MCH) and alpha-melanocyte stimulating hormone (alpha-MSH) in the mammalian brain were investigated by intraventricular administration of these substances in rats. MCH increased food intake and lowered plasma glucocorticoids while alpha-MSH has the opposite effects. MCH and alpha-MSH antagonize each other when both are present and one is in excess.