Type 2 diabetes (T2D) is a significant medical, social, and economic problem worldwide [1]. Regardless of age or other situations, T2D can cause macrovascular and microvascular damage, leading to various functional impairments throughout the body. Atherosclerotic cardiovascular disease (ASCVD) have been commonly found in patients with T2D, such as cerebral vascular accident (CVA), coronary heart disease (CHD), and peripheral artery disease (PAD) [2].

Dietary therapy is fundamental, and low-carbohydrate diet (LCD) has been recognized for T2D [3].  LCD was initiated in Western countries since clinical introduction by Drs. Atkins and Bernstein [4-6]. The authors were the first to introduce LCD in Japan. We established the Japan LCD Promotion Association (JLCDPA) and have been promoting the benefits of LCDs through various opportunities [7]. Specifically, JLCDPA proposed the practical application of the Petit, Standard, and Super LCDs [8]. They continue to provide diagnosis, treatment, and education in clinical settings.

Meanwhile, various effective oral hypoglycemic agents (OHAs) have recently been used for clinical practice [9]. Among these, metformin has been widely used as the first-line treatment worldwide for long years [10]. Recently, in Japan, DPP4-i agents are frequently applied due to the Asian population, body type, responsiveness, and safety. A combination drug including these two medicine has been known as vildagliptin/metformin (EquMet) [11]. It is administered twice daily and is expected to be clinically effective, without any worrying side effects such as hypoglycemia. From mentioned above, the authors et al. have continued clinical care to a variety of diabetic patients. Recently, we encountered a meaningful case, which will be described with related perspectives in this article.

History and Physicals

The current case is 61-year-old male. He was diagnosed as light degree of T2D in middle 50s several years ago, and he did not have treatment for T2D at that time. In spring 2023, he visited another clinic, and was pointed out elevated HbA1c value. In September 2023, He developed acute back pain and was transferred to our hospital by the ambulance. He was diagnosed with right ureteral stones and T2D with hospitalization and starting OHAs. During 2023-2025, his diabetic control has been rather changing around HbA1c 6.6-7.4%.

For his physical examination, vital signs, consciousness, lung, heart, abdomen and neurological findings are unremarkable. Concerning his stature, he was healthy with 57kg in body weight during 20s period. After that, his weight has gradually increased during 30s-50s, and the max weight was 70kg in middle 50s. Currently, his weight has been 68.1kg in weight, 164cm in stature, and 25.3 kg/m² in BMI. 

Several Examinations

Clinical progress of biochemical data is shown in Table 1. He revealed normal range of liver/renal function and complete blood count for years. Elevated triglyceride was due to post-prandial blood drawing. As to diabetic markers, he continued to have hyperglycemia and elevated HbA1c values. Chest X-P was negative and Electrocardiogram (ECG) showed ordinary sinus rhythm (OSR), pulse 76/min, and unmarkable ST-T changes. Urinalysis revealed negative results as protein (-), urobilinogen (+/-), glucose (+++), occult blood (+/-), pH 7.0, bilirubin (-) and ketone bodies (-).

Table 1: Progress of Biochemistry Data.

He received the exam of pulse wave velocity (PWV) (Figure 1). As a result, Cardio-Ankle Vascular Index (CAVI) revealed 9.8/9.6 (right/left), where their values were more than standard range for 7.9 +/- 0.7. However, the data were situated as increased level as the applicant is 60s for age. The value of ankle-brachial index (ABI) was 1.11/1.16 (right/left), for normal range of 0.91-1.40. Consequently, he showed arteriosclerosis situation for 60s for age. The detail markers for PWV showed that L (126) = L1 (64) + L2 (34) + L3 (28), PEP 77, ET 283, R-AI 0.98 and PEP/ET 0.27.

Figure 1: Result of Pulse Wave Velocity (PWV).

He underwent abdominal CT scan (Figure 2). The results indicated the presence of fatty liver and cholelithiasis. Mild enlargement of the right kidney and enlargement of the renal pelvis were noted, along with fuzziness at the margins. Small stones were suspected at the base of the right ureter and near the right ureteral orifice in the bladder. Mild enlargement of the prostate was also noted.

Figure 2: Images of Abdomen CT scan

1. fatty liver
2. cholelithiasis
3. arteriosclerosis of the aorta
4. remarkable visceral fat

Clinical Progress and Medical Problems

He has been treated in the out-clinic of our hospital for 2 years. The patient was treated as T2D and hypertension. He was provided EquMet HD (combination of Equa 100mg/day and Metformin 1000mg/day) and Amlodipine 5mg/day for years. His control for T2D and hypertension has been almost stable.

From his history, exams and clinical data, his medical problems can be summarized as follows. They are i) T2D, ii) hypertension, iii) fatty liver, iv) gall stone, v) mild enlargement of right renal pelvis, vi) previous history of urolithiasis, vii) some stones in urinary tract in current CT scan and viii) normal range of serum uric acid.

Ethical Standards

Current study was complied with the standard guideline of Helsinki Declaration [12]. The commentary was along with the protection for personal information. This principle is based on the ethical rules for the clinical research and practice for human subjects. Certain related guideline is from Ministry of Health, Labour and Welfare, and Ministry of Education, Culture, Sports, Science Technology (MHLW). The authors and collaborators established ethical committee in the Sakamoto Hospital. It included the president, physicians, nurse, registered pharmacist and legal professional. All members discussed in satisfactory manner for this case, agreed research protocol and obtained informed consent from the patient.

This male case appears to be characterized by several problems. The primary problem is T2D, and certain correlations may be present among other problems. The eight medical problems include T2D, HTN, fatty liver, cholelithiasis, renal enlargement, previous urolithiasis, current renal stones, and normal uric acid (UA) value. The perspectives concerning these problems would be discussed below. This patient had no family history of diabetes, and his medical history indicated slow weight gain over some decades. Suspected T2D was identified in his mid-50s. At that time, related medical problems may exist for T2D, fatty liver, and cholelithiasis. He had a long-standing alcohol consumption habit of 1-2 glass of alcohol per day. The case is now 61-years old, and his renal function and serum uric acid level show within the normal range. However, possible influence of UA metabolism can be suggested for the renal enlargement, previous urolithiasis, and current renal stones.

In this case, diabetic treatment was begun based on some information of medical history and BMI at the initial consultation. It continued in the following order: 1) a low-carbohydrate diet (LCD) was started as a nutritional therapy, 2) metformin 500 mg/day was then initiated, followed by 3) vildagliptin 50 mg was added twice daily, 4) metformin was then increased from 500 to 1000 mg twice per day [13]. Since metformin 500 mg and vildagliptin 50 mg can be provided as a combination drug, twice a day, 5) EquMet HD was started to for the clinical progress. One notable feature of this regimen is that both drugs are administered twice daily instead of once daily. Compared to sitagliptin, another once-daily DPP4-i drug, twice-daily administration has been shown to reduce mean blood glucose value and mean amplitude of blood glucose excursions (MAGE) during the nighttime hours [14]. These pharmacological effects are the advantages of Equa and EquMet [15,16].

As for the current case, the male patient could fully understood the contents of the LCD, but he wished to consume a certain amount of rice for dinner every day. Considering the patient's lifestyle, actual contents of three meals, and satisfactory consent for diabetic treatment, it was rather ideal prescription that vildagliptin suppressed blood glucose elevations from late at night to the morning. From mentioned above, the administration of EquMet seemed to be clinically meaningful and effective. Concerning clinical efficacy of EquMet, well-known large trials were conducted, which was Vildagliptin Efficacy in combination with metfoRmIn for early treatment of type 2 diabetes (VERIFY) [17]. Several reports have been found for clinical effect of EquMet [18]. Related study for EVER-Vilda was also investigated [19]. Consequently, generally combined treatment of LCD and pharmacotherapy will bring better QOL, mental health and well-being for patients with T2D [20].

Certain limitation may exist for this article. This case is likely to have eight medical problems as mentioned. However, other possible impaired function would be present, which are not detected yet. Along with his clinical course from now, some issue possibly will be clarified. For example, arteriosclerosis due to T2D and hypertension may develop ASCVD including CVA, CHD and PAD in the future.

In summary, 61-year-old male with T2D, hypertension and other medical problems was described with some perspectives. Current case will be carefully followed up in the future.

Conflict of Interest

The authors have no conflicts of interest to declare.

Funding

There was no funding received for this paper.

1. ADA Professional Practice Committee. 1. Improving Care and Promoting Health in Populations: Standards of Care in Diabetes—2025. Diabetes Care. 2024; 48: S14-S26.
2. Abdellatif M, Schmid ST, Fuerlinger A, Kroemer G. Anti-ageing interventions for the treatment of cardiovascular disease. Cardiovasc Res. 2024: 121: 1524-1536.
3. Ichikawa T, Okada H, Hironaka J, Nakajima H, Okamura T, Majima S, et al. Efficacy of long-term low carbohydrate diets for patients with type 2 diabetes: A systematic review and meta-analysis. J Diabetes Investig. 2024; 15: 1410-1421.
4. Atkins RC. Dr. Atkins' New Carbohydrate Gram Counter. M. Evans and Company. 1996.
5. Bernstein RK. Dr. Bernstein's Diabetes Solution. Little, Brown and company, New York. 1997.
6. Ebe K, Wood M and Bando H. In Memory of Dr. Richard K. Bernstein, April 17. Int J Endocrinol Diabetes. 2025; 8: 1-2.
7. Muneta T, Hayashi M, Nagai Y, Matsumoto M, Bando H, Ebe K, et al. Ketone Bodies in the Fetus and Newborn During Gestational Diabetes and Normal Delivery. Int J Diabetes. 2023; 5: 157-163.
8. 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.
9. American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025. Diabetes Care. 2024; 48: S181-S206.
10. Bando H. Metformin as First-Line Agent for Type 2 Diabetes (T2D) with Various Beneficial Aspect. Int J Endocrinol Diabetes. 2024; 7: 1-3.
11. Arakawa T, Bando H, Ogawa H, Nagahiro S, Nakanishi M, and Watanabe O. Clinical Improvement by Vildagliptin/Metformin (Equmet) For Diabetic Patient with Remarkable Arteriosclerosis from Slight Hba1c Elevation for Years. Int J Case Rep Clin Image 2023; 5: 1-4.
12. 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.
13. Bailey CJ. Metformin: Therapeutic profile in the treatment of type 2 diabetes. Diabetes Obes Metab. 2024; 26: 3-19.
14. Marfella R, Barbieri M, Grella R, Rizzo MR, Nicoletti GF, Paolisso G. Effects of vildagliptin twice daily vs. sitagliptin once daily on 24-hour acute glucose fluctuations. J Diabetes Complications. 2010; 240: 79-83.
15. Bando H, Iwatsuki N, Okada M, Ogawa T and Sakamoto K. Relieved Type 2 Diabetes (T2D) By Petite Low Carbohydrate Diet (LCD), Equmet and Twymeeg. J Biomed Sci Res. 2024; 6: 1-4.
16. Ogawa T, Bando H, Iwatsuki N, Okada M, Sakamoto K. Remarkable Effects for HbA1c and Weight by Twymeeg (imeglimin) and EquMet in Type 2 Diabetes (T2D) Patient. SunText Rev Endocrine Care. 2024; 4: 1-4.
17. Matthews DR, Palda´nius PM, Proot P, Chiang YT, Stumvoll M, Prato SD, et al. Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial. Lancet. 2019; 394: 1519-1529.
18. Bando M, Takeuchi Y, Okumura M, Nagao N, Sakai K, Bando H, et al. Beneficial efficacy for type 2 diabetes (T2D) and Metabolic syndrome (Met-S) by vildagliptin/metformin (EquMet). Int J Endocrinol Diabetes. 2023; 6: 1-4.
19. Kalra S, Zargar AH, Sridhar GR, Das AK, Ahmed J, Mohan JC, et al. Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective. Clin Med Insights Endocrinol Diabetes. 2024; 17: 1-12.
20. Arsalandeh F, Shemirani F, Nazari MA, Mirmiran P, Golzarand M. Effect of low-carbohydrate diets on quality of life, mental health, and speed of memory in adults: a systematic review and meta-analysis of randomised controlled trials. Int J Food Sci Nutr. 2025; 76: 4-19.