Real-world clinical evidence of oral semaglutide on metabolic abnormalities in subjects with type 2 diabetes: a multicenter retrospective observational study (the Sapporo-Oral SEMA study).

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m2) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

Impact of low-starch high-fiber pasta on postprandial blood glucose.

BACKGROUND AND AIMS: Almost all of the energy in noodle dishes is derived from carbohydrates, particularly starch. Recently, we invented a pasta with reduced starch content to about 50% and increased dietary fiber content, designated low-starch high-fiber pasta (LSHFP). In this study, we investigated the ingestion of LSHFP on the postprandial glucose response as a breakfast meal. METHODS AND RESULT: This was a randomized, single-blinded, crossover study. The postprandial glucose area under the curve for 4 h (4h-gluAUC), as the primary outcome, and the extent of postprandial glucose elevation (maxΔBG) were evaluated using a continuous glucose monitoring system in healthy volunteers and patients with type 2 diabetes (T2DM) after intake of LSHFP, standard pasta (SP), and rice. The amount of total carbohydrate was matched between LSHFP and SP. Ten individuals with T2DM and 10 individuals who did not have T2DM and were otherwise healthy were enrolled in this crossover study. The 4h-gluAUC for LSHFP (137.6 ± 42.2 mg/dL・h) was significantly smaller than the 4h-gluAUC for rice (201.7 ± 38.7 mg/dL・h) (p = 0.001) and SP (178.5 ± 59.2 mg/dL・h) (p = 0.020). The maxΔBG for rice (118.6 ± 24.2 mg/dL) was significantly higher than those for SP (87.5 ± 19.9 mg/dL) (p < 0.001) and LSHFP (72.7 ± 26.2 mg/dL) (p = 0.001), while the maxΔBG for LSHFP (p = 0.047) was significantly lower than that for SP, in T2DM patients as well as in healthy participants. CONCLUSIONS: This study demonstrated that LSHFP can reduce postprandial glucose elevation compared with SP in both healthy participants and patients with T2DM.

Acromegaly Cases Exhibiting Increased Growth Hormone Levels during Oral Glucose Loading with Preadministration of Dipeptidyl Peptidase-4 Inhibitor.

Objective Glucose-dependent insulinotropic polypeptide (GIP) is speculated to worsen growth hormone (GH) hypersecretion in acromegaly and to be a cause of paradoxical increases in GH (PI-GH) during 75-g oral glucose tolerance testing (75-g OGTT). Dipeptidyl peptidase-4 inhibitors (DPP4is), which increase the circulating concentration of active GIP, are frequently administered to diabetic patients, including those with acromegaly. We aimed to determine whether or not the administration of a DPP4i increases GH concentration, especially in patients demonstrating PI-GH during a DPP4i-OGTT, in which a DPP4i was administered immediately before 75-g OGTT. Methods This prospective cross-sectional study was carried out on acromegalic patients admitted to Hokkaido University hospital between June 2011 and May 2018. The participants underwent both 75-g OGTT and DPP4i-OGTT. For those who underwent surgery, immunohistochemical staining and quantitative polymerase chain reaction (PCR) for the GIP receptor (GIPR) were performed on the resected pituitary adenomas. Results Twenty-five percent of the participants had PI-GH confirmed (3 of 12 cases). Two of the three participants who demonstrated PI-GH exhibited higher circulating GH concentrations during DPP4i-OGTT than during OGTT. The increase in plasma glucose was reduced during DPP4i-OGTT compared to during 75-g OGTT, suggesting that the increase in GH during DPP4i-OGTT was due not to high glucose concentrations but instead increased GIP caused by the administration of DPP4i. The adenoma from one participant with PI-GH displayed positive immunostaining for GIPR and a higher GIPR messenger ribonucleic acid (mRNA) expression than the others. Conclusion DPP4i may enhance the GH secretion response during glucose loading, especially in individuals with PI-GH.

Combination of alcohol and glucose consumption as a risk to induce reactive hypoglycemia.

AIMS/INTRODUCTION: Alcohol consumption has been reported to cause hypoglycemia. However, the mechanism involved has not been unequivocally established. This study comprised healthy volunteers. We carried out a prospective trial to compare the effects of glucose and alcohol consumption, alone or in combination, on glucose and lipid metabolism. MATERIALS AND METHODS: A 75-g oral glucose tolerance test (OGTT), a combined 75-g glucose plus 20-g alcohol tolerance test (OGATT) and a 20-g alcohol tolerance test (OATT) were carried out in the participants. Plasma glucose, insulin, triglyceride and ethanol concentrations during each test were compared. RESULTS: We studied 10 participants. Their plasma glucose concentrations 15 and 30 min after the intake of 75 g of glucose were significantly higher during the OGATT than the OGTT. Hypoglycemia occurred in five participants after the OGATT, which was significantly more frequently than after the OGTT (P = 0.046). Hypoglycemia did not occur after the OATT, and the ethanol concentration was significantly lower after the OGATT than the OATT. The changes in triglyceride concentration from 30 min after the consumption of 75 g of glucose were significantly greater during the OGATT than the OGTT. The plasma insulin concentrations peaked after 60 min during both the OGTT and OGATT, and were significantly higher during the OGATT (P = 0.047). There were no differences between the two interventions in the Matsuda or disposition indexes. CONCLUSIONS: Hypoglycemia occurred more frequently after the simultaneous consumption of alcohol plus glucose than after the consumption of glucose alone, suggesting that alcohol in the combination of glucose induces reactive hypoglycemia.

Effects of Switching from Liraglutide or Dulaglutide to Subcutaneous Semaglutide on Glucose Metabolism and Treatment Satisfaction in Patients with Type 2 Diabetes: Protocol for a Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group Comparison Study (The SWITCH-SEMA 1 Study).

INTRODUCTION: Glucagon-like peptide (GLP)-1 receptor agonists exert potent hypoglycemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent manner. Once-weekly subcutaneous administration of the GLP-1 receptor agonist semaglutide has beneficial effects on glycemic and body weight control, but it is currently unclear if semaglutide provides superior glycemic control compared to conventional GLP-1 receptor agonists in the Japanese population. We aim to compare the effects of once-weekly subcutaneous semaglutide with those of liraglutide or dulaglutide administration in Japanese patients with T2D. METHODS: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group trial. In total, 100 participants with T2D who have been treated with liraglutide (0.9-1.8 mg/day in plan A) or dulaglutide (0.75 mg/week in plan B) for more than 12 weeks and have a glycated hemoglobin (HbA1c) level of 6.0-9.9% and a body mass index (BMI) of ≥ 22 kg/m2 will be randomized to either continue using their existing GLP-1 receptor agonist or switch to subcutaneous semaglutide once weekly for 24 weeks. Biochemical analysis, physical assessment, and a quality-of-life questionnaire (DTSQ) will be completed at baseline and at the end of the study. The primary endpoint is the effect of semaglutide on the change in HbA1c. The secondary endpoints are the mean changes in total DTSQ score, body mass, abdominal circumference, systolic and diastolic blood pressure, pulse rate, factors associated with improvement in HbA1c and secondary endpoints, side effects, and other laboratory parameters. PLANNED OUTCOMES: The results of the study will provide useful information regarding the effects of switching to semaglutide from other GLP-1 receptor agonists on glycemic control in patients with T2D. ETHICS AND DISSEMINATION: The Hokkaido University Certified Review Board (CRB no. 1180001) has approved the protocol (no. 018-005). The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION: UMIN000042369 in the University Hospital Medical Information Network (UMIN); jRCT1011200008 in the Japan Registry of Clinical Trials (jRCT); pre-results.

Switching to Once-Daily Insulin Degludec/Insulin Aspart from Basal Insulin Improves Postprandial Glycemia in Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial.

BACKGROUND: To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM). METHODS: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks. RESULTS: Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (-1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P<0.05). Intriguingly, glycemic control after breakfast was not improved by IDegAsp injection before breakfast, in contrast to the favorable effect of injection before dinner on blood glucose after dinner. Glycosylated hemoglobin significantly decreased only in the IDegAsp group (58 to 55 mmol/mol, P<0.05). Changes in daily insulin dose, body mass, and recorded adverse effects, including hypoglycemia, were comparable between groups. CONCLUSION: IDegAsp was more effective than basal insulin at reducing blood glucose after dinner and before bedtime, but did not increase the incidence of hypoglycemia. Switching from basal insulin to IDegAsp does not increase the burden on the patient and positively impacts glycemic control in patients with T2DM.