Aim:The study aim was to evaluate the efficacy and safety of initial combination therapy with saxagliptin þ metformin vs. saxagliptin or metformin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycaemic control. Methods: In this multicentre, randomized, double-blind, active-controlled phase 3 trial, 1306 treatment-naïve patients with T2D !18 to 77 years, glycosylated haemoglobin (HbA1c) !8 to 12%, fasting C-peptide concentration !1.0 ng/ml, body mass index 40 kg/m 2 were randomized to receive saxagliptin 5 mg þ metformin 500 mg, saxagliptin 10 mg þ metformin 500 mg, saxagliptin 10 mg þ placebo or metformin 500 mg þ placebo for 24 weeks. From weeks 1-5, metformin was uptitrated in 500-mg/day increments to 2000 mg/day maximum in the saxagliptin 5 mg þ metformin, saxagliptin 10 mg þ metformin and metformin þ placebo treatment groups. The main outcome measure was HbA1c change from baseline to week 24. Selected secondary outcomes included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA1c <7% and postprandial glucose area under the curve (PPG-AUC).Results: At 24 weeks, saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin demonstrated statistically significant adjusted mean decreases vs. saxagliptin 10 mg and metformin monotherapies in HbA1c (À2.5 and À2.5% vs. À1.7 and À2.0%, all p < 0.0001 vs. monotherapy) and FPG (À60 and À62 mg/dl vs. À31 and À47 mg/dl, both p < 0.0001 vs. saxagliptin 10 mg; p ¼ 0.0002 saxagliptin 5 mg þ metformin vs. metformin; p < 0.0001 saxagliptin 10 mg þ metformin vs. metformin). Proportion of patients achieving an HbA1c <7% was 60.3 and 59.7%, respectively, for saxagliptin 5 mg þ metformin and saxagliptin 10 mg þ metformin (all p < 0.0001 vs. monotherapy). PPG-AUC was significantly reduced [À21 080 mgÁmin/dl (saxagliptin 5 mg þ metformin) and À21 336 mgÁmin/dl (saxagliptin 10 mg þ metformin) vs. À16 054 mgÁmin/dl (saxagliptin 10 mg) and À15 005 mgÁmin/dl (metformin), all p < 0.0001 vs. monotherapy]. Adverse event occurrence was similar across all groups. Hypoglycaemic events were infrequent. Conclusion: Saxagliptin þ metformin as initial therapy led to statistically significant improvements compared with either treatment alone across key glycaemic parameters with a tolerability profile similar to the monotherapy components.
In the present study, we performed a meta-analysis to assess the ability of leucine supplementation to increase the muscle protein fraction synthetic rate and to augment lean body mass or leg lean mass in elderly patients. A literature search was conducted on Medline, Cochrane, EMBASE and Google Scholar databases up to 31 December 2013 for clinical trials that investigated the administration of leucine as a nutrient that affects muscle protein metabolism and muscle mass in elderly subjects. The included studies were randomised controlled trials. The primary outcome for the meta-analysis was the protein fractional synthetic rate. Secondary outcomes included lean body mass and leg lean mass. A total of nine studies were included in the meta-analysis. The results showed that the muscle protein fractional synthetic rate after intervention significantly increased in the leucine group compared with the control group (pooled standardised difference in mean changes 1·08, 95 % CI 0·50, 1·67; P, 0·001). No difference was found between the groups in relation to lean body mass (pooled standardised difference in mean changes 0·18, 95 % CI 20·18, 0·54; P¼ 0·318) or leg lean mass (pooled standardised difference in mean changes 0·006, 95 % CI 2 0·32, 0·44; P¼ 0·756). These findings suggest that leucine supplementation is useful to address the age-related decline in muscle mass in elderly individuals, as it increases the muscle protein fractional synthetic rate. Key words: Essential amino acids: Elderly: Dietary supplements: SarcopeniaAgeing is accompanied by a progressive decline in muscle mass and strength (sarcopenia) and is associated with a lower quality of life due to the reduced ability of an individual to perform daily living activities (1) . It also predisposes people to the development of chronic metabolic disorders such as diabetes and obesity (2) . The prevalence of sarcopenia differs by sex and living settings (3) . For example, age-related muscle loss has been reported to be prevalent in about 68 % of elderly men and 21 % of elderly women living in nursing homes (4,5) , but in about 10 % of men and 33 % of women living in the community (4,6)
The new oxyselenide La(2)Co(2)Se(2)O(3), containing Co(2)O square-planar layers, has been successfully synthesized using solid-state reactions under vacuum. The compound crystallizes in space group I4/mmm with lattice parameters a = 4.0697(8) A and c = 18.419(4) A. Magnetic susceptibility measurements indicate an antiferromagnetic transition at approximately 220 K. The magnetic entropy associated with the transition is close to R ln 2, suggesting an unusual low-spin state for the Co(2+) ions. The as-prepared sample shows insulating behavior with room-temperature resistivity of approximately 10(7) ohms cm, which decreases by 4 orders of magnitude under a pressure of 7 GPa. Band structure calculations using the LSDA+U approach reproduce the insulating ground state with low spin for Co and suggest strong orbital polarization for the valence electrons near the Fermi level. It is also revealed that the spin and orbital degrees of freedom in the antiferromagnetic checkerboard spin-lattice are mutually coupled.
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