Aims/hypothesis The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. Methods This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA 1c 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA 1c . Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n=232), liraglutide placebo (n=115) and open-label insulin glargine (n=234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.Electronic supplementary material The online version of this article (doi:10.1007/s00125-009-1472-y) contains a list of members of the LEAD-5 Study Group, which is available to authorised users. Results The number of patients analysed as intention to treat were: liraglutide n=230, placebo n=114, insulin glargine n= 232. Liraglutide reduced HbA 1c significantly vs glargine (1.33% vs 1.09%; −0.24% difference, 95% CI 0.08, 0.39; p= 0.0015) and placebo (−1.09% difference, 95% CI 0.90, 1.28; p<0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p=0.0001), and vs glargine (treatment difference −3.43 kg, 95% CI 4.00, 2.86; p<0.0001). Liraglutide reduced systolic BP (−4.0 mmHg) vs glargine (+0.5 mmHg; −4.5 mmHg difference, 95% CI 6.8, −2.2; p=0.0001) but not vs placebo (p=0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. Conclusions/interpretation Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA 1c was within the predefined non-inferiority margin.

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Increased urinary albumin excretion is a strong predictor for the development of overt diabetic nephropathy and overall cardiovascular morbidity and mortality in patients with type 2 diabetes. In a previous study, regular aerobic physical activity in overweight/obese patients with type 2 diabetes mellitus was found to have significant beneficial effects on glycemic control, insulin resistance, cardiovascular risk factors, and oxidative stress. The aim of the present study was to investigate the effects of aerobic exercise in the same cohort of type 2 diabetic patients on urinary albumin excretion, serum levels and urinary excretion of enzymes, tubular damage, and metabolic control markers in type 2 diabetic patients. Changes from baseline to 3 and 6 months of aerobic exercise were assessed for urinary albumin excretion, serum activities, and urinary excretion of N-acetyl-beta-D-glucosaminidase (NAGA), plasma cell glycoprotein 1 (PC-1) and aminopeptidase N (APN), as well as their association with insulin resistance, cardiovascular risk factors, and oxidative stress parameters in 30 male type 2 diabetic patients (aged 54.8 +/- 7.3 years, with a mean BMI of 30.8 +/- 3.0 kg/m2). Microalbuminuria was found in six (20%) diabetic patients at baseline, three of them (10%) after three months, and only one patient (3.33%) at the end of the study period. A significant correlation was found for urinary albumin excretion at baseline both with sulfhydryl-groups and catalase, but not for urinary albumin excretion with MDA and glutathione. The prevalence of microalbuminuria tended to decrease after six months of aerobic exercise in type 2 diabetic patients, independently of any improvement in insulin resistance and oxidative stress parameters. Neither between-group nor within-group changes were found for urinary PC-1, APN, and NAGA activity. Serum NAGA was significantly increased (p< 0.05) over the control level in diabetic patients at baseline, but it decreased to the normal level after six months of exercise. This study has shown that a six-month aerobic exercise, without any change in the medication, tended to decrease microalbuminuria without changing enzymuria. However, further studies are needed not only to confirm those findings, but to elucidate potential mechanisms that would clarify the beneficial effects of exercise.

Diabetes mellitus (DM) and chronic periodontitis are common chronic diseases in adults in the world population. DM has a strong influence on the oral cavity and represents a risk factor for gingivitis and periodontitis. Low-level laser therapy (LLLT) has proven effective in the reduction of inflammation and swelling. The aim of the present study was to evaluate the efficacy of LLLT in diabetic periodontitis through histological analysis. A total of 300 diabetics with chronic periodontal disease and teeth indicated for extraction were assigned into six equal groups. In the groups 1 and 4, indicated teeth were extracted before treatment, and in the rest of the groups upon completion of the entire treatment. All patients received oral hygiene instructions and full-mouth conservative periodontal treatment. In groups 3 and 6, LLLT was applied (670 nm, 5 mW, 2 J/cm(2), 16 min, 5 days). Histologic findings of gingival tissue treated with LLLT showed expressed healing, as is evident by the absence of inflammatory cells. Tissue edema could not be seen, and the number of blood vessels was reduced. In the gingival lamina, propria pronounced collagenization and homogenization were present. It can be concluded that LLLT has shown efficacy in the treatment of periodontitis in diabetics. Because of more pronounced alterations of periodontium in diabetics, the use of LLLT is of particular importance.

Adding BIAsp30 to met in obese patients with T2DM results in better glycemic control and less weight gain than adding BHI30.