For decades, diabetes has been crucial disease to manage adequately in any country and district. WHO Global Diabetes Compact has initiated for tackling the increasing burden of diabetes [1]. It sets up visionary 2030 target for obtaining health outcomes. Actually, lots of patients with type 2 diabetes (T2D) suffer from microangiopathy and macroangiopathy. The latter includes arteriosclerosis of three main organs, which are cerebral vascular accident (CVA), ischemic heart disease (IHD), and peripheral artery disease (PAD). Such cardiovascular risk should be always investigated carefully in diabetic patients [2]. American Diabetes Association (ADA) has presented standards of care every year, and the information would be the fundamental and optical method.

Concerning the nutritional treatment for diabetes, recent eating habit and food consumption situation may bring health problems [3]. Among various diet therapies, low carbohydrate diet (LCD) has been highly evaluated for diabetes and obesity [4]. Authors and collaborators have firstly initiated LCD in Japan, and developed LCD medically and socially through Japan LCD promotion association (JLCDPA) [5]. We have proposed useful and simple three LCD meal as petite-LCD, standard-LCD and super-LCD with carbohydrate ratio of 40%, 26% and 12%, respectively [6]. From recent study, LCD can have various beneficial efficacy for not only metabolic control, but also immunity and anti-cancer effect [7].

Regarding diabetic pharmacology, recent topic would be imeglimin (Twymeeg), which is the novel oral hypoglycemic agent (OHA) [8]. It can stimulate insulin secretion from pancreas and decrease insulin resistance in the liver and muscle [9]. From many reports, imeglimin presented satisfactory clinical efficacy for better blood glucose variability in T2D patients [10]. Improved diabetic control will bring the protection of developing or delaying the arteriosclerosis [11].  Author’s medical team has treated various diabetic patients so far, and an impressive male case recently showed remarkable clinical effect. His general situation with some perspectives are discussed in this article.

Medical History

The patient is 59-year-old male with T2D and obesity. In the health check-up on July 2024, he was pointed out to have diabetes as HbA1c 7.2%. For the last health check-up in July 2020, HbA1c was in the normal range as 5.6%. In comparison, body weight and BMI in 2020 vs 2024 were 77.2 kg vs 80.2 kg, and 28.9 kg/m² vs 29.6 kg/m², respectively. He visited our clinic in October 2024, and HbA1c was 8.0%. He was advised to start LCD and OHA treatment for T2D.

Physicals and Several Exams

Physical examination in Oct 2024 revealed in the following: speech and consciousness were normal, and his vital signs were unremarkable as BP 138/82 mmHg, pulse 80, SpO2 99%. No changes were observed in the face, head, lung, heart, abdomen or extremities. His physique showed 164.6cm, 80.6kg, and BMI 29.7 kg/m².

Medical progress of blood biochemistry is summarized from 2020 to 2025 in Figure 1. It showed elevated HbA1c values, elevated TG and subnormal level of hemoglobin. Chest X-ray revealed negative, and Electrocardiogram (ECG) showed pulse 78/min, regular, ordinary sinus rhythm (OSR), and no specific ST-T changes.

Figure 1: Changes in Blood Chemistry.

The exam of pulse wave velocity (PWV) was conducted (Figure 2).  Bilateral ankle-brachial index (ABI) revealed 1.20/1.17 (right/left), respectively, which were within normal range more than 0.9 [12]. The result of brachial-ankle pulse wave velocity (baPWV) showed 1783/1751. Optimal normal range would be 1400-1800 cm/sec for general people, but the data were higher value according to the age as 59 years old [13] (Figure 3).

Figure 2: Result of Pulse Wave Velocity.

Figure 3: Presence of Arteriosclerosis.

Clinical Progress

After evaluation of clinical situation and diagnosis, LCD was immediately started as nutritional treatment. Successively, some OHAs were initiated in the following order. They are i) imeglimin (Twymeeg) 2000mg/day from October, ii) empagliflozin (Jardiance) 10mg from November, and iii) empagliflozin 25mg/day from December. The clinical progress is summarized in Figure 4, including the changes in HbA1c and body weight. HbA1c has decreased in satisfactory manner to 6.1% for 6 months, and to 5.8% for 12 months. No significant gastro-intestinal adverse effect (GI-AE) were observed during the course.

Figure 4: Clinical Progress of the Case.

Ethical Standards

This report is complied with the Helsinki Declaration [14]. Some commentary meant the protection for personal right. The principle reveals the ethical rule of human subjects for clinical research. Necessary guideline is from the Ministry of Education, Culture, Sports, Science Technology and the Ministry of Health, Labour and Welfare. Authors and colleagues established the ethical meeting in Kanaiso Hospital that includes director, internist, surgeon, nurse, pharmacist, dietician and legal professional. We have discussed the protocol enough, agreed it, and obtained the informed consent of the patient.

From primary care point of view, this case has some characteristic aspects. He showed remarkable effects for HbA1c reduction from 8.0% to 5.8%, and weight reduction from 82.6kg to 72.1kg for 12 months. These improvements may be from the following 4 factors, which are i) LCD for nutritional therapy, ii) imeglimin with double mechanism of insulin-secreting and reduction of insulin resistance, iii) empagliflozin as sodium-glucose cotransporter 2-inhibitor (SGLT2-i), and iv) his stable lifestyle with working hard and diligently every day.

The current case has some characteristic aspects from internal medicine point of view. They are T2D, obesity, fatty liver, probable existing arteriosclerosis from PWV exam. During T2D treatment from 2024, he has understood well, continued stable life with LCD, leading to current satisfactory improvement of T2D.

Furthermore, the patient has other medical and psychological problems. He has visited neurosurgery clinic for years, which include epilepsy with sometimes convulsive seizures [15]. Furthermore, he has been treated by schizophrenia with stable condition for long [16]. He has continued some medicines as phenytoin (Aleviatin) 700mg/day and haloperidol (Serenace) 6mg/day. These medicine has been provided in neurosurgery clinic, and no remarkable symptom, sign or changes were found for a decade. Body weight has increased with slow pace for decades. From mentioned above, these neurosurgery and related matters are possibly involved in diabetes onset or exacerbation.

As related reports, some discussion has been found for the relationship of schizophrenia and developing T2D [17]. A meta-analysis was conducted using medical subject headings (MeSH) for 32 observational studies involving 2 million cases with schizophrenia for 20 years. As a result, pooled analysis showed significant relationship between schizophrenia history and T2D risk as odds ratio (OR) = 2.15. When stratified by gender, OR revealed 2.12 in females, and 1.68 in males with significant difference. These findings suggest that that schizophrenia may become an independent risk for T2D.

For PWV exam, this case showed normal ABI and high baPWV and Percentage of Mean Arterial Pressure (%MAP) [18]. As an important marker, %MAP has been known and used for the examination and evaluation for arteriosclerosis. This case showed the data of %MAP 48%/49% for upper extremities, and 30%/32% for lower extremities. For the data of %MAP, usual standard range would be less than 45%. If the result is more than 45%, the case possibly has stenosis or obstruction of arteries. General evaluation with the obtained data of ABI, baPWV and %MAP would be recommended for the diagnosis and treatment. In the case of such management, Japan Atherosclerosis Society (JAS) has presented the Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022 [19].

As a novel OHA, imeglimin (Twymeeg) has clinical efficacy from lots of international reports. Author have presented impressive cases by the administration of imeglimin so far [20]. This case showed remarkable HbA1c improvement by imeglimin and empagliflozin. As some international large trials, Trials of IMeglimin for Efficacy and Safety (TIMES) have reported the effects of combined treatment, in which TIMES 1 and 3 were reported [21,22]. In TIMES 2 report, they compared clinical efficacy of combined treatment in the following. They are -0.46% for monotherapy, -0.67% for biguanide, -0.57% for SGLT2-i, and -0.12% for GLP-1RA [23]. From this evidence, the current case showed larger improvement associated with other additional beneficial factors.

Certain limitation possibly exists for this article. The combined therapy of imeglimin and SGLT2-i was clinically effective [24]. In addition, some other factors may be involved in the improvement of the clinical progress. We have to treat and follow up this case for long with careful attention.

In conclusion, 59-year-old diabetic male was presented in the light of bio-psycho-social aspects. It includes diabetes, imeglimin, LCD, neurosurgery and daily lifestyle. Current report will be expected to become useful reference in the future.

Conflict of interest

The authors declare no conflict of interest.

Funding

There was no funding received for this paper.

1. Lim LL, Khunti K. Global inequality in target attainment among people with diabetes. Lancet Glob Health. 2026; 14: e2-e3.
2. American Diabetes Association Professional Practice Committee for Diabetes*. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. Diabetes Care. 2026; 49: S216-S245.
3. Akter MN, Jahan N, Biswas BC, Hasan S, Abdullah M, Hasan MM, et al. Impact of fast-food consumption on public health: A comparative study between urban and rural peoples. J Curr Res Food Sci. 2025; 6: 471-478.
4. Kusayev J, Weininger D, Frishman WH, Aronow WS. Low-Carbohydrate/Ketogenic Diet and Coronary Artery Disease: A Brief Review of the Limited Evidence between Them. Cardiol Rev. 2026; 34: 53-56.
5. Ebe K, Wood M, Bando H. In Memory of Dr. Richard K. Bernstein, April 17. Int J Endocrinol Diabetes. 2025; 8: 1-2.
6. Bando H, Ebe K. Beneficial and Convenient Method of Low Carbohydrate Diet (LCD) as Petite, Standard and Super LCD. Asp Biomed Clin Case Rep. 2023; 7: 1-4.
7. Wood M,  Bando  H, Ebe  Immune  Function  Augmentation  in  Low-Carbohydrate  Diet  (LCD). Int  J Endocrinol Diabetes. 2025; 8: 1-6.
8. Shireen SM, Bhavya E, Parthiban R. Imeglimin systematic review: a novel therapeutic approach for type 2 diabetes-unveiling benefits on β-cell function, insulin sensitivity, and potential long-term glycaemic control (HbA1c). Eur J Clin Pharmacol. 2025; 81: 1713-1731.
9. Hou T, Zhang J, Shi W. Mechanisms and clinical perspectives on imeglimin for insulin resistance in obese patients. Eur J Pharmacol. 2025; 1003: 177937.
10. Mori K, Bando H, Urasaki H, Kobayashi H, Nagahiro S. Changes In Insulinogenic Index (Igi) For Glucose Tolerance Test (Gtt) During Taking Imeglimin (Twymeeg). IntJ Case Rep Clin Image. 2025; 7: 1-5.
11. Bando H, Okada M, Ogawa T, Iwatsuki N, Sakamoto K. Multiple Arteriosclerosis with Type 2 Diabetes (T2D) Treated By Imeglimin (Twymeeg). Int J Endocrinol Diabetes. 2026; 9: 1-5.
12. Tanaka A, Tomiyama H, Maruhashi T, Matsuzawa Y, Miyoshi T, Kabutoya T, et al. Physiological Diagnostic Criteria for Vascular Failure. Hypertension. 2018; 72: 1060-1071
13. Fukui T, Ishizaka Y, Masuda I, Kato K, Muto S, Atarashi T. The correlation between brachial-ankle pulse wave velocity?baPWV?and atherosclerosis risk factors, as well as the risk score for development of atherosclerotic diseases in Ningen Dock health checkup: a prospective collaborative study at six health checkup facilities. Ningen Dock International. 2024; 11: 47-54.
14. General Assembly of the World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Coll Dent. 2014; 81: 14-28.
15. Tayutivutikul N, Wanleenuwat P, Panapongvasin T, Klajing R, Iwanowski P. Dietary effects on antiseizure drug metabolism and management of epilepsy. Seizure. 2022; 102: 14-21.
16. Friedrich M, Fugiel J, Sadowska J. Assessing Effects of Diet Alteration on Carbohydrate-Lipid Metabolism of Antipsychotic-Treated Schizophrenia Patients in Interventional Study. Nutrients. 2023; 15: 1871.
17. Dong K, Wang S, Qu C, Zheng K, Sun P. Schizophrenia and type 2 diabetes risk: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024; 15: 1395771.
18. Gupta A, Singh R, Bhadada SK, Jude EB, Rastogi A. Ankle brachial index and brachial-ankle pulse wave velocity as predictor for major adverse limb events and all-cause mortality in diabetes. Diabetes Metab Syndr. 2025; 19: 103239.
19. Okamura T, Tsukamoto K, Arai H, Fujioka Y, Ishigaki Y, Koba S, et al. Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022. J Atheroscler Thromb. 2024; 31: 641-853.
20. Bando H, Iwatsuki N, Okada M, Ogawa T, Sakamoto K. Relieved Type 2 Diabetes (T2D) By Petite Low Carbohydrate Diet (LCD), Equmet and Twymeeg. J Biomed Sci Res. 2024; 6: 1-4.
21. Dubourg J, Fouqueray P, Thang C, Grouin JM, Ueki K. Efficacy and Safety of Imeglimin Monotherapy Versus Placebo in Japanese Patients With Type 2 Diabetes (TIMES 1): A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multicenter Phase 3 Trial. Diabetes Care. 2021; 44: 952-959.
22. Reilhac C, Dubourg J, Thang C, Grouin JM, Fouqueray P, Watada H. Efficacy and safety of imeglimin add-on to insulin monotherapy in Japanese patients with type 2 diabetes (TIMES 3): A randomized, double-blind, placebo-controlled phase 3 trial with a 36-week open-label extension period. Diabetes Obes Metab. 2022; 24: 838-848.
23. Dubourg J, Fouqueray P, Quinslot D, Grouin JM, Kaku K. Long-term safety and efficacy of imeglimin as monotherapy or in combination with existing antidiabetic agents in Japanese patients with type 2 diabetes (TIMES 2): A 52-week, open-label, multicentre phase 3 trial. Diabetes Obes Metab. 2021; 24: 609-619
24. Bando H, Iwatsuki N, Okada M, Ogawa T, Sakamoto K. A Diabetic Case of Occasional Hemorrhoidal Bleeding with Clinical Improvement by Imeglimin (Twymeeg). Int J Case Rep Clin Image. 2026; 7: 1-5.