Pharmacological Characteristic of Imeglimin (Twymeeg) For Dual Mechanism to Insulin Secretion and Resistance

Latest Standards of Medical Care in Diabetes was presented in January 2022. Among oral hypoglycemic agents (OHAs), imeglimin has been topic for a novel agent for type 2 diabetes mellitus (T2DM). Pharmacologically, imeglimin is a cyclic molecule including triazine ring. It has both pharmacological mechanism of increased insulin action and elevation of glucose-stimulated insulin secretion (GSIS). Clinically, it showed HbA1c reduction for 0.46% by monotherapy and 0.56-0.92% by combined therapy with other OHAs. From compared administration of 500mg, 1000mg and 1500mg, 1000mg twice doses would be adequate. No remarkable treatment-emergent adverse events (TEAEs) were found for treatment of imeglimin

Seven Kinds of Intermediate Filament Networks in the Cytoplasm of Polarized Cells: Structure and Function

Intermediate filaments (IFs) are involved in many important physiological functions, such as the distribution of organelles, signal transduction, cell polarity and gene regulation. However, little information exists on the structure of the IF networks performing these functions. We have clarified the existence of seven kinds of IF networks in the cytoplasm of diverse polarized cells: an apex network just under the terminal web, a peripheral network lying just beneath the cell membrane, a granule-associated network surrounding a mass of secretory granules, a Golgi-associated network surrounding the Golgi apparatus, a radial network locating from the perinuclear region to the specific area of the cell membrane, a juxtanuclear network surrounding the nucleus, and an entire cytoplasmic network. In this review, we describe these seven kinds of IF networks and discuss their biological roles

Investigation for Daily Profile of Blood Glucose by the Administration of Canagliflozin and Xultophy (IdegLira)

Background: American Diabetes Association (ADA) presented 2022 guideline, and indicated the benefit of sodium-glucose transporter 2 inhibitor (SGLT2i) and glucagon-like peptide 1 receptor agonist (GLP-1RA). Xultophy is a combined agent of insulin degludec/liraglutide (IDegLira), which is recently clinically useful. Patient and Method: The case is 72-year-old man with type 2 diabetes mellitus (T2DM). He has been treated by some oral hypoglycemic agents (OHAs) with unstable HbA1c levels. Results: When HbA1c was 9.9% in 2018, his daily profile of blood glucose three times a day ranged 208-289 mg/dL. By starting canagliflozin, blood glucose decreased for 145-194 mg/dL. As HbA1c increased to 8.8% in 2021, blood glucose ranged 179-192 mg/dL. By starting Xultophy 12 doses per day, it decreased to normal level for 73-155 mg/dL. HbA1c was reduced to 6.7% half year later. Changes in eGFR showed the decrease from 80 to 51 mL/min/1.73 m2 during unstable HbA1c period in 2018-2019, and stable 50-60 mL/min/1.73 m2 during stable HbA1c period in 2020-2021 with Xultophy therapy. Discussion: SGLT2i, GLP-1RA and Xultophy seem to be beneficial for cardiovascular and renal function. Furthermore, these agents seem to be adequate for diabetic patients with chronic kidney disease (CKD) and/or diabetic kidney disease (DKD)

Improvement of Obesity and Type 2 Diabetes (T2D) by Oral Semaglutide (Rybelsus) and Super-Low Carbohydrate Diet (LCD)

For novel oral hypoglycemic agent (OHA), semaglutide (Rybelsus) has been attracted attention. Patient is 41-year-old hospital staff with obesity, who was pointed out 7.7% of HbA1c with weight 101kg in June 2020. He continued petite-low carbohydrate diet (LCD) for 8 months with weight reduction 3kg. Successively, he applied super-LCD for 7-months and showed 7kg reduction and HbA1c 5.6% in Sept 2021. He took Rybelsus 3mg per os from Mar 2022 and showed 88kg and 5.5% in Nov 2022. LCD brought improvement of ALT from 97 to 27 U/L for 30 months. Thus, LCD and Rybelsus showed satisfactory clinical effect

Acute Improvement of Glucose Variability by Oral Semaglutide (Rybelsus) and Low Carbohydrate Diet (LCD) In Type 2 Diabetes (T2D) Patient with Ophthalmic Operation

Background: Oral semaglutide (Rybelsus) has been in focus as glucagon-like-peptide 1 receptor agonist (GLP1-RA). Case presentation: Patient is 40-year-old male with diagnosed as type 2 diabetes (T2D). He complained of blurred vision in April 2022, and showed HbA1c 12.0%. He was transferred to university hospital for ophthalmic operation of proliferative vitreoretinopathy and our clinic for diabetic control. He was initiated Rybelsus 3mg/day and super-low carbohydrate diet (LCD) associated with normalized glucose profile in short period. Discussion: This case showed satisfactory clinical efficacy for HbA1c 8.7% and 6.6% in 4 and 8 weeks, and weight reduction 6kg for 3 months

Early elderly male with type 2 diabetes (T2D) changed from metformin to imeglimin (Twymeeg)

Background: Imeglimin (Twymeeg) is latest focus of oral hypoglycemic agent (OHA). Case presentation: Current case is 69-year-old male with type 2 diabetes (T2D) for 18 years. Result: HbA1c value increased to 7.6% in Sept 2022, and then metformin 750mg/day was changed to imeglimin 2000mg/day. HbA1c decreased to 6.9% for 4 months. Discussion and conclusion: Large study of Trials of IMeglimin for Efficacy and Safety (TIMES) showed beneficial efficacy for combined treatment of OHAs. Imeglimin has dual effects increasing insulin secretion and reducing insulin resistance. Perspectives concerning pharmacological effects of metformin and imeglimin are described in diabetic practice and research

Improved HbA1c value by combined treatment of Dulaglutide and Imeglimin for patient with type 2 diabetes mellitus (T2DM)

Background: As a novel oral hypoglycemic agent (OHA), imeglimin has been recently applied for patients with type 2 diabetes mellitus (T2DM) as Twymeeg. It has beneficial twin mechanisms associated with increasing insulin secretion, and decreasing insulin resistance. It has a triazine ring and become the first OHA for tetrahydrotriazine-containing agent in the category of the glimins. Case presentation: The case is 84-year-old female with T2DM and mild cognitive impairment (MCI). Her HbA1c was 9.3% a year ago. Results: She was begun to receive Dulaglutide 0.75mg/week and showed 1.3% HbA1c reduction for 6 months. However, HbA1c was elevated again to 8.5%, and then she was provided Twymeeg 2000mg/day. HbA1c decreased from 8.5% to 7.5% in 3 months. [Discussion and conclusion] From combined treatments of imeglimin and other agents in the previous study, mean HbA1c reduction showed single imiglimin -0.46%, DPP-4i -0.92% and GLP-1RA -0.12%. Possible reason for the difference between the latter two suggests that multiple action mechanisms of imeglimin may be present including the enhancement of glucose-stimulated insulin secretion (GSIS). In contrast, she showed satisfactory HbA1c reduction by the combination of imeglimin and GLP-1RA. The pathophysiology is not clear, and future follow up the clinical progress will be required