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.

O besity and abdominal adiposity have been shown in prospective studies to be risk factors for cardiovascular disease and particularly for diabetes (1-8). In cross-sectional studies, both are related with risk factors for these diseases (9 -12), but there are few publications on the effects of changes in abdominal adiposity (13). We characterized men and women who gained and lost abdominal adiposity over 9 years and describe the incidence and the improvement in cardiometabolic risk factors according to changes in waist circumference. RESEARCH DESIGN AND METHODS -From the Data from anEpidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort (9,14,15), 1,868 men and 1,939 women aged 30 -64 years at baseline were followed over 9 years. The 73% of the baseline cohort that we studied were older, less frequently abdominally obese, hypertriglyceridemic, hyperinsulinemic, smokers, and fewer had metabolic syndrome. Cardiometabolic abnormalities and the metabolic syndrome were defined according to the National Cholesterol Education Program (NCEP) criteria (16), except high blood pressure, which included antihypertensive treatment (Table 1); hyperinsulinemia was defined by upper quartiles of fasting insulin Ն57.3 pmol/l for men and Ն52.8 pmol/l. The incidence and improvement of cardiometabolic risk factors were studied by age-adjusted logistic regression, according to waist change: Յ Ϫ3.0 cm, Ϫ2.9 to ϩ2.9 cm, 3.0 -6.9 cm, and Ն7.0 cm. Statistical significance was defined as P Ͻ 0.05.RESULTS -The median increase in waist circumference was 3 cm in men and 4 cm in women; 25 and 34% of men and women, respectively, increased their waist by Ն7 cm, 14% decreased their waist by Ն3 cm, and 29% remained stable (Ϯ2.9 cm).Men whose waist decreased were older and had a larger waist circumference and BMI at baseline. Age was not significantly related to waist change in women; however, women who became slimmer had a larger baseline waist but similar BMI. Men who decreased alcohol intake reduced their waist circumference. Stopping smoking was associated with an increase in waist circumference, but smoking at baseline was associated with a gain in waist circumference in only men. Baseline physical activity did not influence waist change, but an increase was associated with a decreasing waist circumference.The incidence of abdominal obesity was 10% in men and 15% in women (Table 1). Of all risk factors, high blood pressure had the highest incidence (48 and 30%, respectively), and the incidences of the metabolic syndrome were 8% for men and 7% for women. The metabolic syndrome and all cardiometabolic factors showed significant trends that became worse with an increasing waist (with one exception, LDL cholesterol in women). The odds ratios (95% CI) for an incident metabolic syndrome were 7.9 (4.4 -13.9) in men and 4.7 (2.7-8.0) in women who increased their waist by Ն7 cm, compared with a stable waist circumference. Results were not changed after adjusting for baseline waist circumference or BMI. Adjusting for 9-year BMI change, ...

Objective: Previous evidence has suggested that a low sex hormone-binding globulin (SHBG) concentration is associated with insulin-resistance and a low adiponectin concentration. We investigated the association between SHBG and the risk of hyperglycemia in each sex and we determined potential interactions between SHBG and adiponectin levels in the development of dysglycemia. Design: We used a nested case-control design in the large prospective study, Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). We studied 227 men and women who were normoglycemic at baseline but hyperglycemic at 3 years (glycemiaR6.1 mmol/l or type 2 diabetes). They were matched for sex, age, and body mass index with 227 subjects who remained normoglycemic at 3 years. Results: At baseline, the concentration of SHBG was significantly lower in women who subsequently developed hyperglycemia than in those who remained normoglycemic, with no difference for men. In multiple regression, SHBG at baseline was as an independent determinant of plasma adiponectin levels, in both women (P!0.0001) and men (PZ0.002). In multivariate conditional logistic regression taking into account physical activity and changes in waist circumference over the follow-up, plasma SHBG remained significantly associated with the development of hyperglycemia in women but not in men. These associations persisted after adjustment for fasting insulinemia, high fasting glucose, and adiponectin levels. Conclusions: These findings suggest that a low SHBG level is a strong risk marker for dysglycemia in women, independently of both adiponectinemia and insulinemia. SHBG may therefore improve the identification of women at risk of diabetes.