Aims/hypothesis The aim of this 52-week, open-label, noninferiority trial was to compare the safety and efficacy of exenatide (an incretin mimetic) with that of biphasic insulin aspart. Materials and methods Patients on metformin and a sulfonylurea were randomised to exenatide (n=253; 5 μg twice daily for 4 weeks, 10 μg thereafter) or biphasic insulin aspart (n=248; twice-daily doses titrated for optimal glucose control), while continuing with metformin and sulfonylurea treatment.Results Glycaemic control achieved with exenatide was non-inferior to that achieved with biphasic insulin aspart (mean±SEM, HbA 1c change: exenatide −1.04± 0.07%, biphasic insulin aspart −0.89±0.06%; difference −0.15 [95% CI −0.32 to 0.01]%). Exenatide-treated patients lost weight, while patients treated with biphasic insulin aspart gained weight [between-group difference −5.4 (95% CI −5.9 to −5.0) kg]. Both treatments reduced fasting serum glucose (exenatide −1.8±0.2 mmol/l, p<0.001; biphasic insulin aspart −1.7±0.2 mmol/l, p<0.001). Greater reductions in postprandial glucose excursions following morning (p < 0.001), midday (p = 0.002) and evening meals (p<0.001) were observed with exenatide. The withdrawal rate was 21.3% (54/253) for exenatide and 10.1% (25/248) for biphasic insulin aspart. Nausea (33% incidence, 3.5% discontinuation) was the most common adverse event observed with exenatide. Conclusions/interpretation Exenatide treatment resulted in HbA 1c reduction similar to biphasic insulin aspart and provided better postprandial glycaemic control, making it a potential alternative for the treatment of type 2 diabetes. Treatment with biphasic insulin aspart was associated with weight gain and lower risk of adverse gastrointestinal events. Although the availability of glucose-lowering agents associated with weight reduction may be considered a therapeutic advance, the long-term implications of progressive weight reduction observed with exenatide have yet to be defined.

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OBJECTIVE -To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes.RESEARCH DESIGN AND METHODS -Subjects (n ϭ 322) who were pregnant or planning pregnancy were randomized to IAsp or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C Յ8% at confirmation of pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C Ͻ6.5%. Outcomes assessed included risk of major maternal hypoglycemia, A1C, plasma glucose profiles, and maternal safety outcomes. A total of 80% of subjects achieved an A1C Յ6.5%. At the end of first and third trimesters, average postprandial plasma glucose increments were significantly lower with IAsp than HI (P ϭ 0.003 and P ϭ 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P ϭ 0.044 and P ϭ 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments. RESULTSCONCLUSIONS -IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia. Diabetes Care 30:771-776, 2007

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on behalf of the Spanish TRIC-1 (Treatment of Resistance to Insulin in Hepatitis C Genotype 1) group Insulin resistance affects sustained virological response (SVR) in chronic hepatitis C. To know whether adding metformin to standard antiviral treatment improves SVR, we conducted a prospective, multicentered, randomized, double-blinded, placebo-controlled trial in 19 Spanish hospitals, including 123 consecutive patients with genotype 1 chronic hepatitis C and insulin resistance. Patients were randomized to receive either metformin (arm A; n ‫؍‬ 59) or placebo (arm B; n ‫؍‬ 64) in addition to peginterferon alfa-2a (180 g/week) and ribavirin (1000-1200 mg/day). The primary end point was SVR, and secondary endpoints were viral clearance at weeks 12, 24, and 48, and changes in the homeostasis model assessment (HOMA) index over the first 24 weeks. There were no differences between arms at baseline. In the intent-to-treat analysis, SVR was observed in 53% versus 42% in arm A and arm B, respectively (P ‫؍‬ NS). In the subgroup analyses, SVR was higher in females (n ‫؍‬ 54) receiving metformin: arm A, 58% (15/26) versus 29% (8/28) arm B (P ‫؍‬ 0.03). In the per protocol analysis (PPA; n ‫؍‬ 101), SVR was 67% in arm A and 49% in arm B (P ‫؍‬ 0.06). Viral decline during the first 12 weeks was greater in females receiving metformin: ؊4.88 (1.18) versus ؊4.0 (1.44) (P ‫؍‬ 0.021), whereas no differences were seen in males. The triple therapy was well tolerated, but diarrhea was more often seen in arm A (34% versus 11%; P < 0.05). Conclusion: Adding metformin to peginterferon and ribavirin was safe and improved insulin sensitivity. Although the study failed to show a statistically significant difference between arms, it did show an improved SVR in females. (HEPATOLOGY 2009;50:1702-1708