ABSTRACT
INTRODUCTION: It is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i. METHODS: Sixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics. RESULTS: HbA1c was significantly lower at week 24 (- 1.0 ± 0.9% in the IGlar group and - 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (- 2.9 ± 3.2% vs. - 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. - 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups. CONCLUSION: For poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial. TRIAL REGISTRATION: Trial Registry (UMIN-CTR) as UMIN000012224.
ABSTRACT
The purpose of this study was to investigate the hormonal regulation of gummosis in grape hyacinth (Muscari armeniacum) bulbs, focusing especially on the chemical composition of the gums. The application of ethephon (2-chloroethylphosphonic acid), an ethylene-releasing compound, at 1% and 2% (w/w) in lanolin as well as ethylene induced gummosis in the bulbs within several days. Methyl jasmonate (JA-Me, 0.1-2% in lanolin) alone had no effect on gummosis. However, simultaneous application of JA-Me and ethephon led to extreme stimulation of ethephon-induced gummosis. Ethephon-induced gummosis in the bulbs depended on the maturation stage of the bulbs, increasing from April to July, but decreasing from August to September. Regardless of the presence of JA-Me, the application of ethephon to the inflorescence axis of grape hyacinths did not induce gummosis. Gel permeation chromatography analysis revealed that gums were homogenous polysaccharides with an average molecular mass of ca. 8.3 kDa. Analysis of the sugar composition of the gums after hydrolysis revealed that the molar ratio of Rha:Ara:Gal:GalA:GlcA was 25:10:40:7:15. These results suggest that principal factors of gummosis as well as the chemical composition of gums differ between species of bulbous plants.
