Background: As an oral hypoglycaemic agent (OHA), imeglimin (Twymeeg) has been recently introduced to clinical practice for patients with type 2 diabetes mellitus (T2DM) as Twymeeg. It has beneficial pharmacological mechanisms, which are improving insulin secretion, increasing insulin sensitivity, and decreasing insulin resistance. Case Presentation: The case is 84-year-old man with mild cognitive impairment (MCI) for 3 years. He visited late August, 2021 our clinic for general malaise and was pointed out to have post-prandial blood glucose 336 mg/dL and HbA1c 8.6%. He was diagnosed with T2DM. Results: He was started to be given imeglimin 1000mg twice a day, and then HbA1c value was decreased to 7.3% in 4 weeks and 5.7% in 8 weeks. During 9-12 weeks, he felt loss of appetite and reduced food intake. Biochemical examination on 12 weeks showed decreased values of TP, Alb, HbA1c, glucose, free T3, and normal values of TSH, free T4. Doses of imeglimin were 500 mg twice a day for 9-12 weeks and discontinued after 12 weeks. Discussion: Regarding appetite loss, possible causes may include MCI, previous history of gallbladder dyskinesia, adverse effect of imeglimin, and so on. Further development of research will be expected for imeglimin in the future.

The case was 52-year-old female with type 2 diabetes mellitus (T2DM) for 10-years. She complained of the decreased sensation of right lower foot, and revealed diabetic foot infection (DFI) and/or diabetic foot osteomyelitis (DFO) at right 1 st proximal phalanx. Various data included body mass index (BMI) 33.3 kg/m 2 , HbA1c 11.4%, blood glucose 430 mg/dL, WBC 12100 /μL, C-reactive Protein (CRP) 13.5 mg/dL. On admission (day 1), she was started by 4 times of injection (Aspart and Glargin) with glucose profile 200-500 mg/dL. Surgical amputation of the right toe was performed between 1 st metatarsal and proximal phalanx (day 17). Then, blood glucose profile decreased moderately. After discharge of the hospital, super-Low Carbohydrate Diet (LCD) was started without Aspart (day 37). Consequently, glucose profile was normalized with HbA1c 6.3% on (day 77). Consequently, LCD was evaluated to be effective for glucose variability in this case and some related discussion was described.

The case is a 69-year-old male patient with Type 2 Diabetes Mellitus (T2DM) for 21 years. His diabetic control was not so satisfactory, and his HbA1c value increased in spring 2021. Then, he started Xultophy (IDegLira), which includes a fixed ratio of two agents of basal degludec and liraglutide. Just after providing Xultophy, the daily profile of blood glucose decreased from 179-400 mg/dL to 112-171 mg/dL, with remarkable clinical efficacy. He usually takes 80g of carbohydrates in breakfast, and the meal tolerance test (MTT) was challenged. As carbohydrate loading was given 100-75-50-0%, postprandial hyperglycemia at 60-min showed 277-219-159-133 mg/dL, respectively.

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Two patients with Type 2 Diabetes Mellitus (T2DM) were treated with Xultophy. Xultophy consists of degludec and liraglutide (IDegLira). It is the combination of long-acting insulin and Glucagon like Peptide-1 Receptor Agonist (GLP-1RA) and is characteristic for effective agent for improving glucose variability for patients with T2DM. However, clinical responses are not always satisfactory due to different complication and background of each patient. We have experienced two impressive T2DM cases. Case 1 was 59-year-old male with hypertension for 20 years and T2DM for 3 years. He was treated on Novolin 30R 30/21 units twice a day, and after that Xultophy 32 doses brought him successful glucose profile. Case 2 was 78-year-old male with hypertension, bronchial asthma, hyperuricemia, and others with heavy alcohol drinking for 50 years. He was formerly treated by Insulin detemir, Liraglutide, exenatide and Degludec/NovoRapid, but has been recently unstable in glucose control. Xultophy up to 40 doses could not successfully improve glucose variability. One of the less responsiveness to Xultophy would be due to impaired liver function. Clinical progress of both cases associated with several perspectives from various points of view are discussed in this article.