SUMMARY BackgroundCurrently, although only a few therapies normalize the liver test abnormalities with ⁄ without improving the liver histology, no pharmacologic therapy has proved to be effective for the treatment of non-alcoholic steatohepatitis.

Objective: To directly compare the efficacy and safety of a fixed-ratio combination, iGlarLixi, with a premix insulin analog (BIAsp 30) as treatment advancement in type 2 diabetes suboptimally controlled on basal insulin plus oral antihyperglycemic drugs (OADs). ResearchDesign and Methods: SoliMix, a 26-week, open-label, multicenter study, randomized adults with suboptimally controlled basal insulin-treated type 2 diabetes (HbA 1c ≥7.5 % and ≤10 %) to once-daily iGlarLixi or twice-daily BIAsp 30. Primary efficacy endpoints were non-inferiority in HbA 1c reduction (margin 0.3 %) or superiority in bodyweight change for iGlarLixi versus BIAsp 30. Results: Both primary efficacy endpoints were met: after 26 weeks, baseline HbA 1c (8.6 %) was reduced by 1.3 % with iGlarLixi and 1.1 % with BIAsp 30, meeting non-inferiority (least squares [LS] mean difference [97.5% CI]: -0.2 [-0.4, -0.1] %; p<0.001). iGlarLixi was also superior to BIAsp 30 for bodyweight change (LS mean difference [95% CI] -1.9 [-2.3, -1.4] kg) and percentage of participants achieving HbA 1c <7 % without weight gain and HbA 1c <7 % without weight gain and without hypoglycemia (all p<0.001). iGlarLixi was also superior versus BIAsp 30 for HbA 1c reduction (p<0.001). Incidence and rates of ADA Level 1 and 2 hypoglycemia were lower with iGlarLixi versus BIAsp 30.Conclusions: Once-daily iGlarLixi provided better glycemic control with weight benefit and less hypoglycemia than twice-daily premix BIAsp 30. iGlarLixi is a more efficacious, simpler, and well-tolerated alternative to premix BIAsp 30 in suboptimally controlled type 2 diabetes requiring treatment beyond basal insulin plus OAD therapy.

Endemic goiter is an important public health problem in Turkey. Legislation for mandatory iodization of household salt was passed in July 1999. Current study is aimed at ascertaining the goiter prevalence and iodine nutrition in school-age children (SAC) living in known endemic areas of Turkey. Sonographic thyroid volumes (STV) and urinary iodine concentrations (UIC) of 5,948 SAC from 20 cities were measured between 1997-1999. STV of 31.8% of the SAC examined stayed above the upper-normal limits for the same age and gender recommended by the World Health Organization (WHO). Goiter prevalence ranged between 5 to 56% and median UIC ranged between 14 to 78 microg/l, indicating severe to moderate iodine deficiency (ID) in 14 and mild ID in 6 of the cities surveyed. Neither of the cities was found to have sufficient median UIC levels. The current study shows that endemic goiter is an important public health problem and iodine nutrition is inadequate nationwide. It also provides reliable scientific evidence and shows the need for a controlled and effective iodine supplementation program nationwide. Mandatory iodization of household salt seems to be the essential measure taken for the moment, additional measures may be needed in the near future.

Abstract. Subclinical Cushing's syndrome (SCS) is being detected with increased frequency in patients with adrenal incidentaloma. In the current study, we evaluated the prevalence of SCS in 70 patients with adrenal incidentaloma and compared the main findings on them with other patients with nonfunctional adrenal incidentaloma (NFA). Overnight 3 mg dexamethasone (DXM) suppression test to exclude cortisol hypersecretion, and high dose DXM suppression test to find out patients with SCS, were applied to all subjects. Afterwards, biochemical and clinical findings of patients with SCS were compared with the other patients with NFA. Four of the 70 patients with adrenal incidentaloma were found to have SCS, with a prevalence of 5.7%. Basal ACTH and DHEA-S levels were significantly lower (p<0.05 and p<0.01, respectively), and midnight cortisol and 24-hour urinary free cortisol levels were significantly higher in patients with SCS (p<0.001 and p<0.05, respectively). Biochemical and metabolic bone parameters were similar in patients with SCS and in patients with NFA. Hypertension, diabetes mellitus, and obesity were more common in patients with SCS. One of the patients with SCS developed adrenocortical insufficiency following unilateral adrenalectomy which lasted for about 6 months. Suppressed ACTH and DHEA-S levels, and high midnight cortisol levels may be some clues for SCS in patients with adrenal incidentaloma. Since patients with SCS frequently have risk factors for atherosclerosis such as hypertension, diabetes, and obesity, and the surgical management of SCS with adrenalectomy may offer an advantage. Patients undergoing adrenalectomy should be followed for the development of adrenal insufficiency.

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Aim Premix insulin is commonly used in some regions of the world, despite the higher risk of hypoglycaemia and weight gain compared with basal insulin, based on the premise that it offers a simplified insulin regimen. iGlarLixi is a once‐daily titratable fixed‐ratio formulation that combines basal insulin glargine 100 units/mL (iGlar) and the GLP‐1 RA, lixisenatide, which offers a single‐injection option for treatment intensification, with improved HbA1c reductions, similar hypoglycaemia risk and more favourable bodyweight profiles over iGlar alone. This randomized controlled study directly compares, for the first time, treatment intensification with iGlarLixi versus premix insulin analogue biphasic insulin aspart 30 (BIAsp 30) in adults with T2D inadequately controlled on basal insulin in combination with one or two oral antihyperglycaemic drugs. Materials and Methods This was an open‐label, active‐controlled, comparative, parallel‐group, multicentre, phase 3b study. In total, 887 adults with T2D uncontrolled on basal insulin were randomized to switch to either iGlarLixi once daily, or BIAsp 30 twice daily, for 26 weeks. Results Overall, 887 participants were enrolled (mean age 59.8 years, 50.2% female) from 89 centres in 17 countries. At baseline, 65.6% had a duration of T2D of 10 years or longer, and the mean HbA1c at baseline was 8.6%. Conclusions The study directly compared the efficacy and safety of iGlarLixi versus BIAsp 30 in people with T2D uncontrolled on basal insulin and one or more oral antihyperglycaemic agents. These results provide robust clinical data that may inform clinicians in their therapeutic management of people with T2D uncontrolled on basal insulin requiring additional therapy.

These results represent the first patient-reported dataset on hypoglycemia in the participating countries and confirm that hypoglycemia is under-reported and more widespread than previously believed. Although the incidence of hypoglycemia was variable among patients on different treatment regimens, there were substantial impacts on both productivity and healthcare utilization following an episode of hypoglycemia. This trial is registered at clinicaltrials.gov: NCT02306681.

The time required to normalize the prevalence of goiter in SAC living in a moderately iodine-deficient environment was at least a decade. To achieve a goiter rate of less than 5% among SAC, it may require that, as a population, they were born and grew up under conditions of iodine sufficiency.