Onset of Type 2 Diabetes (T2D) in Female Case with Low BMI Treated by Imeglimin (Twymeeg)

Bando H, Iwatsuki N, Ogawa T, Okada M and Sakamoto K

Published on: 2026-04-03

Abstract

This patient is 76-year-old slender female of BMI 19.9 kg/m² with type 2 diabetes (T2D). She was previously treated for hypertension, dyslipidemia, and gastroesophageal reflux disease (GERD). In autumn 2024, she was diagnosed with T2D as HbA1c 10.1%. HbA1c decreased to 8.6% in 3 months by low carbohydrate diet (LCD) and Imeglimin (Twymeeg). By addition of empagliflozin from May 2024, HbA1c was 7.2% in December 2024 significant efficacy. Pulse wave velocity (PWV) showed almost standard range compared with the age. The relationship among T2D, sarcopenia, frailty, muscle volume and muscle power has been reported, in which several discussion was described.

Keywords

Gastroesophageal reflux disease (GERD); Low carbohydrate diet (LCD); Gastro-intestinal adverse effects (GI-AE); Pulse wave velocity (PWV); Sarcopenia

Introduction

For decades, aging society has been observed in developed and developing countries and districts worldwide [1]. Then, adequate management for treatment and preventive management would be required. In particular, arteriosclerotic cardiovascular diseases (ASCVDs), non-communicable diseases (NCDs) and lifestyle-related diseases have been in focus in the middle aged and older people [2]. Among them, the prevalence and incidence of diabetes mellitus has been acutely increasing. Consequently, primary care (PC) physicians, family physicians, diabetologist and others have the crucial role for managing those patients. Authors and collaborators have continued diabetic treatment and research for various patients for years [3].

On the other hand, other important health and medical problems would be sarcopenia and frailty in the elderly in the orthopedic department [4]. They are also indispensable disease for comorbidity and complication of diabetes. From PC and diabetes points of view, muscle weakness of those people should be diagnosed, managed and prevented during the follow-up period. Furthermore, it has been reported that both diabetes and sarcopenia show mutually close relationship for onset of either diseased state [5].

Our clinical and diabetic research group has analyzed and presented a variety of medical reports so far [6]. Among them, several activities of low carbohydrate diet (LCD), social movement of Japan LCD promotion association (JLCDPA), educational seminar and research assembly have been continued [7]. Among these situation, we happened to manage a meaningful elderly female case who showed onset of type 2 diabetes (T2D) associated with lower body mass index (BMI). General progress of the cases and related perspectives are described in this article.

Case Presentation

History & Physicals

This case was a 76-year-old female. Previously, she had been receiving medication at another clinic for hypertension, dyslipidemia, and gastroesophageal reflux disease (GERD). In the autumn of 2024, she was pointed out to have type 2 diabetes (T2D) during a health checkup. She visited our department seeking specialized evaluation and treatment for diabetes. Formerly, she had not exhibited any symptoms or signs suggestive of diabetes, and had no other health problems. She was taking four kinds of medications, which were telmisartan, lansoprazole, rosuvastatin, and sennoside.

At her initial visit in autumn 2024, physical examination revealed no abnormalities in vital signs, level of consciousness, head, neck, lung, heart, abdomen, or neurological examination. Her physique measurements were 142.6 cm, 40.5 kg, BMI 19.9 m/kg².

Several Exams

Basic examinations showed no abnormalities, including a negative chest X-ray and no specific ST-T changes in the electrocardiogram (ECG). Complete blood count revealed elevated HbA1c levels of 10.1% and blood glucose levels of 249 mg/dL, leading to a diagnosis of type 2 diabetes (Table 1). No other abnormalities were found in liver, kidney, lipid, or general peripheral blood tests.

Table 1: Progress of the blood chemistry.

			2024		2025
		Units	Mar	Oct	Apr	Sept
Nutrition
	TP	(g/dL)	6.5	6.2	6.1	6.6
	Alb	(g/dL)	4.1	4.0	3.9	4.2
Liver
	AST	(U/L)	22	23	20	21
	ALT	(U/L)	22	23	19	18
	GGT	(U/L)	15	14	9	14
Lipids
	HDL	(mg/dL)	60	63	75	77
	LDL	(mg/dL)	117	107	92	120
	TG	(mg/dL)	126	145	61	87
Renal
	UA	(mg/dL)	2.8	2.6	3.2	2.6
	BUN	(mg/dL)	18	13	16	15
	Cre	(mg/dL)	0.52	0.53	0.54	0.53
	eGFR	(mL/min/1.73m²)	85	83	81	83
CBC
	WBC	(x10^2/μL)	49	48	35	54
	RBC	(x10^4/μL)	445	420	425	427
	Hb	(g/dL)	13.3	12.7	12.9	12.9
	Ht	(%)	41.2	38.5	39.9	39.7
	Plt	(x10^4/μL)	15.8	19.0	19.4	17.9

She underwent pulse wave velocity (PWV, plethysmography). For the biomarker of arteriosclerosis, Cardio-Ankle Vascular Index (CAVI) revealed 10.1/9.9 (R/L, normal range 8.6 +/- 0.8), which was somewhat arteriosclerotic tendency for her age (Figure 1). The value of ankle brachial index (ABI) in plethysmography showed 1.21/1.16 (0.91-1.40), that indicated almost normal ranges and normal R/L difference (Figure 2). The detailed biomarkers showed normal ranges of L (110) = L1 (56) + L2 (30) + L3 (24), PEP 193, ET 354, R-AI 0.97 and PEP/ET 0.26 [8].

Figure 1: The exam of Pulse Wave Velocity (PWV).

Figure 2: CAVI values indicating arterial stiffness.

For the therapeutic methods of T2D, we taught her to continue low carbohydrate diet (LCD), and take the medicine of imeglimin (Twymeeg) 2000mg/day (Figure 3). Consequently, HbA1c value was remarkably decreased for 10.1% to 8.6% for 3 months. After that, HbA1c was stable, and then she was provided empagliflozin from May 2024, in which HbA1c was decreased 7.2% in December 2024 with significant clinical efficacy. She tolerated the continuous intake of Twymeeg, with no symptoms of gastro-intestinal adverse effects (GI-AE) during the clinical progress.

Figure 3: Clinical progress of HbA1c and medication.

Ethical Standards

Current patient complied with the guideline for Declaration of Helsinki [9]. Comments are added for personal information, with the principle of ethical rule for clinical research. Some guidelines were from the regulation for Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare. The authors have established ethic committee in Sakamoto hospital, Kagawa, Japan. The committee has medical staffs, including director, physician, dietician, nurse, pharmacist, and legal professional. We discussed the protocol satisfactory, and the informed consent was obtained from by written document.

Discussion

One of the clinical features of this case is the patient's low BMI, which is associated with the development of diabetes. In recent years, factors such as muscle mass, muscle strength, frailty, and sarcopenia have been reported as involvement in the development of diabetes. Some reports will be introduced concerning healthy individuals and diabetic patients.

As general information, diabetes has been associated with risk of sarcopenia. Clinical research was investigated for whether HbA1c and sarcopenia index may show association in community-dwelling elderly people [10]. The applicants included 18,940 adults with 73.7 years old in mean. As a result, DM group showed association with low muscle strength as OR 1.21 for the adjusted model including BMI. In contrast, DM group did not show a clear association with sarcopenia as OR 1.06, or low muscle mass OR 1.15. Positive correlation was shown between BMI and skeletal muscle index (SMI) (p<0.001). For many adults without diabetes, the associations were studied for glycemic values (HbA1c, glucose) and grip strength (GS) [11]. As the protocol, 381 thousands subjects without diabetes were included and changes in GS over 8.9 years were analyzed into 4 groups, as decline, lower stable, higher stable, or reference. As a result, higher HbA1c (mmol/mol) showed association with weaker GS as regression coefficient -0.08, and increased sarcopenia as odds ratio 1.02 in males and the across-age groups.

There are several reports on the case of patients with diabetes. For the relationship between sarcopenia and diabetes, two kinds of research were conducted [5]. As cohort 1, the association between baseline diabetes and risk of new-onset sarcopenia was examined. As cohort 2, the association between baseline sarcopenia and risk of new-onset diabetes was assessed. As a result, low handgrip strength (OR:2.31) and appendicular skeletal muscle mass index (ASM/Ht²) (OR:1.25) showed association with increasing diabetic risk. In contrast, fasting plasma glucose (FPG) (OR: 1.52) and HbA1c (OR:1.35) showed association with higher sarcopenia risk.

Using Asian Working Group for Sarcopenia (AWGS) 2019 criteria, the prevalence of sarcopenia for Asian T2D patients, and identification of related risk factors were investigated [12]. The protocol was comprehensive systematic review and 39 studies with 19,902 case were analyzed. As a result, pooled prevalence of sarcopenia was 23% among Asian T2D cases, with notably higher rates of 61% for possible sarcopenia and lower rate of 12.1% for severe sarcopenia. Risk factors included odds ratio (OR) for older age 1.13, male 2.37, hypertension 3.65, diabetes duration 1.35, and less physical activity 2.54. In contrast, protective effects were shown for higher BMI 0.63, and more vitamin D values 0.91. Sarcopenia has been reported to have some relationship with cardiovascular autonomic neuropathy (CAN) in T2D. Association of GS, SMI and CAN in T2D patient was studied for 342 subjects [13]. As a result, low muscle strength rather than low muscle mass showed significant association with the presence of CAN. Consequently, GS help identify cases who has benefit from screening for earlier diagnosis of CAN.

International Diabetes Federation (IDF) presented type 5 diabetes (T5D) in April 2025 [14]. T5D has been mainly developed by chronic malnutrition, usually in low-income countries for estimating 20-25 million people [15]. It reveals lower body weight with insulin shortage, that was known previously as malnutrition-related diabetes (MNRD). Its recent perspective typing would bring more discussion and awareness for public health, education, medicine, economy and social factors [16]. Comparing the status of the current case, it is not likely to T5D or MNRD. She has been slender with lower BMI for years, but she keeps her physique for long and her physical, psychological and social situation has been stable with unremarkable changes.

This case has shown remarkable HbA1c decrease by the combination of oral hypoglycemic agents (OHAs). The case was provided, imeglimin, empagliflozin and vildagliptin in this order. Regarding clinical effects of imeglimin, large multi-center studies have been known for international situation. They are Trials of IMeglimin for Efficacy and Safety (TIMES) investigations [17]. From the TIMES 2 data, clinical effect for the combined treatment of imeglimin and other OHAs have been analyzed [18]. They revealed that monotherapy -0.46%, biguanide -0.67%, SGLT2-i -0.57%, α-glucosidase inhibitor (α-GI) -0.85% and DPP4-i -0.92%. In this reported case, she was provided these combination treatment in addition to LCD, and then large decreased value of HbA1c may be found [19].

In summary, the following description and inferences can be drawn from mentioned above. The patient is a 76-year-old female with previously some arteriosclerotic diseases. She developed the onset of T2D in autumn 2024, where her related background were investigated. Possible factor would be the low BMI as 19.9 kg/m², and various previous reports concerning T2D, muscle volume, muscle power, frailty and sarcopenia were discussed. These factors seemed to show mutual relationship each other, but no apparent influencing factors were detected in this case. Currently, glucose variability has been satisfactory, and the case will be followed up with careful attention.

Conflict of Interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

Journal of Biomedical Science and Research