A Network Meta-Analysis Comparing Semaglutide Once-Weekly with Other GLP-1 Receptor Agonists in Japanese Patients with Type 2 Diabetes.

INTRODUCTION: Semaglutide once-weekly (QW) is a novel glucagon-like peptide-1 (GLP-1) analogue administered at a 0.5 or 1.0 mg dose. In the absence of head-to-head trials between semaglutide QW and other GLP-1 receptor agonists (GLP-1 RAs) in a Japanese population, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of semaglutide QW vs GLP-1 RAs in Japanese patients with type 2 diabetes (T2DM), with a specific focus on the comparison between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. METHODS: A systematic review (SR) and supplementary Japanese searches were conducted to identify trials of GLP-1 RAs in Japanese patients on diet and exercise, who have previously received 0-1 oral antidiabetic drugs (OADs). Data at 52-56 weeks were extracted for the following outcomes (feasible for analysis in an NMA): glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), weight, systolic blood pressure (SBP), and overall hypoglycemia. The data were synthesized using an NMA and a Bayesian framework. RESULTS: Four trials, identified from the SR and Japanese-specific searches, were relevant for inclusion in the NMA. When compared to dulaglutide 0.75 mg QW, semaglutide 0.5 mg QW was shown to provide significant reductions in HbA1c [- 0.61% (12.3 mmol/mol)], weight (- 1.45 kg), SBP (- 5.03 mmHg), and FPG (- 1.26 mmol/L). No significant differences in the proportion of patients achieving a HbA1c level < 7% (53 mmol/mol) or the risk of overall hypoglycemia were observed between semaglutide 0.5 mg QW and dulaglutide 0.75 mg QW. CONCLUSION: Overall, semaglutide 0.5 mg QW was associated with significant reductions from baseline in HbA1c, weight, SBP, and FPG compared with dulaglutide 0.75 mg QW in Japanese patients with T2DM. These data may provide valuable evidence for clinical decision-making, cost-effectiveness analyses, and health technology appraisal (HTA) requirements. FUNDING: Novo Nordisk Pharma Ltd.

[Effect of food thickener on disintegration and dissolution of magnesium oxide tablets].

It has been reported that magnesium oxide tablets are excreted in a non-disintegrated state in the stool of patients when the tablets are administered after being immersed in a food thickener. Therefore we examined whether immersion in a food thickener affects the pharmacological effect in patients taking magnesium oxide tablets, and whether immersion affects its disintegration and solubility. The mean dosage (1705 mg/d) was higher for patients who took tablets after immersion in a food thickener than for those who took non-immersed tablets (1380 mg/d). The disintegration time and dissolution rate of the immersed tablets were lower than those of non-immersed tablets in vitro. Furthermore, components that constitute the food thickener and differences in composition concentrations differentially affect the disintegration and solubility of magnesium oxide tablets. This suggests that commercially available food thickeners are likely to be associated with changes in the degradation of magnesium oxide tablets, and they therefore should be carefully used in certain clinical situations.

[Elevated serum lithium concentration due to switch from parenteral nutrition alone to parenteral with enteral nutrition].

We report a patient with elevated serum lithium concentration caused by switching from parenteral nutrition alone to parenteral with enteral nutrition. A 73-year-old female inpatient was treated with lithium carbonate 600 mg/d for manic episodes of bipolar disorder. Her serum lithium level was maintained at 0.57-0.79 mEq/L. She was administered total parenteral nutrition owing to difficulty in oral intake. Her diet contained 4.8-5.8 g/d of sodium chloride. After this, parenteral with enteral nutrition was initiated. The total sodium chloride intake decreased from 6.3 to 3.0-4.0 g/d following this change. On day 15 after initiation of parenteral with enteral nutrition, her serum lithium level increased to 1.17 mEq/L, which is closer to the upper therapeutic range limit. Therefore enteral nutrition was stopped immediately, and an electrolyte solution was administered instead of enteral nutrition. An antibiotic agent was also simultaneously administered because of infection. The total amount of sodium chloride administered was increased to 7.0 g/d during this treatment. Four days after treatment, the serum lithium level returned to 0.57 mEq/L. This case suggests that administration of appropriate sodium chloride nutrition is important during treatment with lithium carbonate, because disposition of lithium ion is paralleled to that of sodium.

[Cesarean section in a morbidly obese parturient with borderline personality disorder under combined spinal and epidural anesthesia].

A 21-year-old morbidly obese parturient with a body mass index of 45.5 kg x m(-2) underwent an emergent cesarean section for obstructed labor under combined spinal and epidural anesthesia. At age 15, she was diagnosed as borderline personality disorder. In spite of the drug therapy, her mental status was unstable. During anesthesia and surgery, her psychiatrist attended beside her to ease her anxiety and mental stress. An experienced anesthesiologist encouraged her and maintained her in the sitting position during epidural catheterization and spinal puncture. The distance between the skin and the epidural space was about 6.5 cm at the L3-4 interspace via midline approach. An epidural catheter was inserted 5 cm cephalad. Subsequently, the L4-5 subarachnoid space was accessed at a depth of about 7.0 cm. A 3 ml bolus of 0.5% hyperbaric bupivacaine was given. The anesthetic level was T4 at the start of the operation. Throughout the surgery, sufficient analgesia was obtained and any complication such as severe hypotension or respiratory depression did not develop and her postoperative course was uneventful.

Facial skin temperature decreases in infants with joyful expression.

Studies of infant emotion rely on the assessment of expressive behavior and physiological response because infants cannot tell their feelings. Little is known about the physiological response of infants when they are in a joyful emotion. In this study, we examined changes in facial skin temperature as a physiological response, when infants are laughing, an expressive behavior of joyful emotion. Using thermography, skin temperatures of the nose, forehead and cheek were evaluated at 2-3 months, 4-6 months and 8-10 months. A decrease in facial skin temperature occurred when they laughed. The decrease was most dramatic in the nose dropping as much as 2.0 degrees C in 2 min. The response was evident in infants older than 4 months. These results suggest that a joyful emotion could be associated with a drop in facial skin temperature, which had been considered only as a sign of an unpleasant emotion. This response is developmentally controlled.

Recognition site for the side chain of 2-ketoacid substrate in d-lactate dehydrogenase.

Replacement of Tyr52 with Val or Ala in Lactobacillus pentosus d-lactate dehydrogenase induced high activity and preference for large aliphatic 2-ketoacids and phenylpyruvate. On the other hand, replacements with Arg, Thr or Asp severely reduced the enzyme activity, and the Tyr52Arg enzyme, the only one that exhibited significant enzyme activity, showed a similar substrate preference to the Tyr52Val and Tyr52Ala enzymes. Replacement of Phe299 with Gly or Ser greatly reduced the enzyme activity with less marked change in the substrate preference. Except for the Phe299Ser enzyme, these mutant enzymes with low catalytic activity consistently stimulated NADH oxidation in the absence of 2-ketoacid substrates. However, the double mutant enzymes, Tyr52Arg/Phe299Gly and Tyr52Thr/Phe299Ser, did not exhibit synergically decreased enzyme activity or the substrate-independent NADH oxidation, but rather increased activities toward certain 2-ketoacid substrates. These results indicate that the coordinative combination of amino acid residues at two positions is pivotal in both the functional recognition of the 2-ketoacid side chain and the protection of the bound NADH molecule from the solvent. Multiplicity in such combinations appears to provide d-LDH-related 2-hydroxyacid dehydrogenases with a great variety of catalytic and physiological functions.