Parallel Change Tendency of HbA1c and LDL-C in Diabetic Patient Treated by Imeglimin (Twymeeg)

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

Published on: 2026-03-05

Abstract

Current patient is 46-year-old male of BMI 26.9 kg/m² with type 2 diabetes (T2D) and dyslipidemia. Family history was positive as younger sister was T2D. Pulse wave velocity (PWV) showed normal ranges of ankle brachial index (ABI) and Cardio-Ankle Vascular Index (CAVI). He has been treated with low carbohydrate diet (LCD) and imeglimin (Twymeeg) for 4 years. In former 2 years, his diabetic control was satisfactory as HbA1c 5.9% and LDL-C 142mg/dL, but HbA1c and LDL-C increased to 8% and 172 mg/dL in last 2 years associated with parallel relationship. He tolerated imeglimin well without gastro-intestinal adverse effects (GI-AE).

Keywords

Low carbohydrate diet (LCD); American Diabetes Association (ADA); Type 2 diabetes (T2D); Pulse wave velocity (PWV); Imeglimin (Twymeeg)

Introduction

For some decades, type 2 diabetes (T2D) has become a major medical and social problem worldwide [1]. American Diabetes Association (ADA) has issued standard guidelines in each year [2]. In actual clinical practice, cerebral vascular accident (CVA), ischemic heart disease (IHD), and peripheral artery disease (PAD) must be managed as macroangiopathy [3]. Therefore, managing diabetes-related arteriosclerosis is crucial [4]. To achieve this, four areas are important for reducing diabetes complications [2]. These are management of glycemic control, blood pressure, lipids, and cardiovascular/kidney benefit [5].

By the development of arteriosclerosis, lifestyle-related disease or atherosclerotic cardiovascular disease (ASCVD) would be increased. It may bring various complications and comorbidities as diabetic pathophysiology [6]. For prevention of ASCVD, adequate management for LDL-cholesterol (LDL-C) would be required. In particular, diabetic patients are evaluated for high-risk group in guidelines [1]. However, the detailed management for dyslipidemia has been not so simple, then various aspects will be controlled in the adequate balance [7]. As lipid control, beneficial points and weak aspects have to be always investigated [8]. Consequently, diabetic cases with dyslipidemia have been present more than expected, and various management would be conducted in the actual medical practice and research [9].

As applicable diet therapy of T2D, low carbohydrate diet (LCD) has been initiated by Bernstein and Atkins in Western countries [8]. Various data for LCD were reported so far compared with calorie restriction (CR), and clinical benefit of LCD has been shown [9]. In Japan, authors’ clinical group has continued medical and social movement of Japan LCD Promotion Association (JLCDPA) [10]. Authors have majored in diabetes and metabolic syndrome (Met-S) for middle and older patients in our diabetic and primary care setting for long [11]. Among them, we have encountered an meaningful male case with diabetes and dyslipidemia. His general situation associated with related perspectives are described in this article.

Case presentation

Medical History

The current case is 46-year-old men with T2D. He has positive family history for T2D, where his younger sister has been treated for T2D for 10 years. As his past history, he became obesity during 20s to 40s for about 30 kg. About 4 years ago, he was diagnosed as T2D, and was provided imeglimin (Twymeeg) at once and also adequate diet therapy of super- LCD. His HbA1c value and weight showed satisfactory reduction during former 2 years, but HbA1c has been rather unstable during last 2 years.

Several Exams

His status praesens in 2023 were unremarkable situation as follows: Consciousness, conversation, and vitals revealed within normal limits. The head, face, neck, heart, lung and abdomen revealed unremarkable. His physique in 2024 showed height 167 cm, weight 75 kg, and BMI 26.9 kg/m². As basic exams, chest X-ray was negative and electrocardiogram (ECG) showed unremarkable without specific ST-T changes.

The clinical progress of his biochemical examination was summarized in Figure 1. It showed the clinical course of HbA1c, blood glucose, liver, renal, lipid functions and complete blood count (CBC).

Blood pressure pulse wave velocity (PWV, plethysmography) was conducted. As the arteriosclerosis biomarker, ankle brachial index (ABI) revealed 1.25/1.24 (right/left, 0.91-1.40), and Cardio-Ankle Vascular Index (CAVI) revealed 7.8/7.4 (right/left, 6.8-8.2), respectively (Figure 2,3). They showed several data within normal ranges, where PEP 76, ET 329. R-AI 0.89 and PEP/ET 0.23 (Figure 2,3). The standard ranges for ABI and CAVI were reported as follows. The ABI has the standard range for > 0.90, and the CAVI has the standard range for > 0.8 [12].

Figure 1: Progress of the relationship between HbA1c and LDL-C.

Figure 2: The result of pulse wave velocity (PWV).

Figure 3: The progress of CAVI.

Clinical Course

HbA1c showed 8.6% in Spring 2023, which was followed by the administration of imeglimin (Twymeeg) for years. In addition, he was advised to continue super-LCD for reduction of HbA1c and body weight. He could continue LCD for about 2 years in satisfactory manner associated with stable HbA1c values. During this period, HbA1c was 5.9-6.2% and LDL was 142-153 mg/dL. However, he could not keep LCD from autumn 2024, and then HbA1c was elevated for several months. Recently, HbA1c has risen to around 8% and LDL has risen to 160-172 mg/dL. He has tolerated the continuation of Twymeeg, without any gastro-intestinal adverse effects (GI-AE) until now. For recent 1 year, he has tried to control regular lifestyle, regular meal pattern with less carbohydrate, and some exercise activity.

Ethical Standards

This patient complied with the guideline for Declaration of Helsinki. Further, comments were observed for personal information. The principle was presented in ethical rule for medical research. Related guidelines were on the regulation for Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labor and Welfare. The authors et al. established the ethic committee for this case, which was in Sakamoto hospital, Kagawa, Japan. The committee has some medical staffs, including director, physician, nurse, pharmacist, dietician, and legal professional. The members have discussed enough the protocol, and the informed consent was obtained from the case.

Discussion

The current case has T2D and dyslipidemia, treated by imeglimin (Twymeeg) for years. His glucose variability became stable by imeglimin and LCD for 2 years, but after that his diabetic control became exacerbation. The reason would be not from imeglimin, but from uncontrolled daily restriction of carbohydrate. As an interesting situation, the value of LDL-C showed some exacerbation in parallel to HbA1c during the period. Concerning these clinical status, some perspectives are described.

Concerning LCD, we have developed three types of useful methods, that can be easily understood by everyone. They are petite-LCD, standard-LCD, and super-LCD, which include carbohydrate ratio as 40%, 26%, and 12%, respectively [13]. The reason of worsened glycemic control in the case would be gradual incomplete LCD continuation, because this case like to eat carbohydrate from childhood. Furthermore, his diabetic sister has same diet behavior. Authors reported LCD research for 2773 obesity cases who were treated by LCD [14]. As a result, weight reduction prevalence was 24.0% for >10% reduction, and 31.2% for 5.0-9.9%.

Regarding imeglimin (Twymeeg), it has been introduced to medical practice for 5 years, where clinical effects have been reported so far. It has specific pharmacological mechanism through mitochondrial route [15]. It may reduce insulin resistance and increase insulin secretion from pancreas [16]. Concerning lipid management for T2D, ADA showed the recommendation in the standard guideline as follows: lifestyle intervention is required, such as physical activity, nutritional treatment [17]. These treatments can reduce ASCVD risk of hypertension, obesity or dyslipidemia. For diet therapy, it recommends reduced saturated and trans fat intake, increased n-3 fatty acid and viscous fiber [18]. Mediterranean or Dietary Approaches to Stop Hypertension (DASH) eating method can be applied for adequate intake of foods [19]. In addition to imeglimin, effective LCD method can be advised to for T2D patients [20]. Some satisfactory clinical progress were reported with combination of imeglimin and LCD therapy [21,22].

Some limitation may be present in this report. Current case showed stable HbA1c course in the former 2 years, and unstable HbA1c situation in the latter 2 years. Its reason would be probably from incomplete continuation of LCD, and other factors showed no changes in his daily lives. Future clinical progress will be carefully followed up.

In summary, general situation of 46-year-old case was presented with some perspectives of T2D, lipid, diet therapy, LCD, imeglimin and so on. Various combined situation will give us novel response and consideration. We hope that current report will provide a useful reference in the future diabetic research.

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