A Diabetic Case of Occasional Hemorrhoidal Bleeding with Clinical Improvement by Imeglimin (Twymeeg)

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

Published on: 2026-01-13

Abstract

The case was a 56-year-old male with type 2 diabetes (T2D), obesity, hypertension and dyslipidemia. By super-low carbohydrate diet (LCD), his BMI decreased from 34.8 to 30.1 kg/m². HbA1c increased to 7.7%, and the imeglimin (Twymeeg) was started. In February 2023, he was asymptomatic and found for anemia 7.9 g/dL and MCV 73.0 fL. The cause was hemorrhoidal bleeding, and he was recovered by taking sodium ferrous citrate. In October 2025, he developed acute heavy hemorrhoidal bleeding with Hb 7.4 g/dL and MCV 90.2fL. He was hospitalized and treated. Currently, he has been stable with treatment for several medical problems.

Keywords

Super-low carbohydrate diet (LCD); Imeglimin (Twymeeg); Sodium ferrous citrate; Trials of IMeglimin for Efficacy and Safety (TIMES); Pulse wave velocity (PWV)

Introduction

Across the world, obesity and diabetes have been important diseases due to developing various complications for years [1]. As the standard guideline, consistent and strong evidence exists that obesity control delays the progression and exacerbation of type 2 diabetes (T2D) [1]. They include both of microangiopathy and macroangiopathy, which are necessary for attention to clinical progress in the future [2]. The complications include lifestyle-related disease or metabolic syndrome (Met-S), such as hypertension, dyslipidemia, hyperuricemia. In addition, atherosclerotic cardiovascular disease (ASCVD) may be developed as macroangiopathy for brain, heart and lower extremities.

From diabetic pharmacological point of view, recent focus includes imeglimin (Twymeeg), which is the novel oral hypoglycemic agent (OHA) [3]. Imeglimin has beneficial aspect for possible combined therapy with other OHAs [4]. This agent shows unique function of both effects for stimulating insulin secretion from pancreatic beta cell, and also reducing the degree of insulin resistance [5,6]. Actually, imeglimin has shown clinical predominance for diabetic patient with various complications [7,8].

Case Presentation

Medical History and Physical Examination

The case was a 56-year-old male with some medical problems. He was diagnosed as T2D, obesity, hypertension, dyslipidemia, bronchial asthma with light degree and low back pain for 10 years. Furthermore, he occasionally experienced hemorrhoidal bleedings during last 8 years, in which he developed anemia and took sodium ferrous citrate for necessary situation.

Physical examination showed unremarkable results of vital signs, speech, consciousness, head, lung, heart, abdomen and neurological findings. His weight was 96kg about 9 years ago with 34.8 kg/m² in BMI. He was educated to start super-low carbohydrate diet (LCD), and continued LCD satisfactory, and then his weight was decreased. Currently, his physique shows 166 cm in height, 83 kg in weight and 30.1 kg/m² in BMI.

Several Examinations

Several fundamental exams were conducted. Chest X-ray revealed unremarkable findings, and Electrocardiogram (ECG) showed regular pulse 72/min, ordinary sinus rhythm (OSR), and unremarkable ST-T changes. Urinalysis revealed that glucose (++), protein (-), urobilinogen (+/-),occult blood (-), pH6.0 and ketone bodies (-).

He underwent the exam of pulse wave velocity (PWV) (Figure 1). It showed the normal ranges of ECG, PCG, bilateral arms and feet. The value of Cardio-Ankle Vascular Index (CAVI) revealed 9.0/9.4 (right/left), where its standard range was approximately 8.6 +/- 0.8. The CAVI values ??on the right correspond to the levels of early 60s, and those on the left correspond to the levels of late 60s (Figure 2). The ankle-brachial index (ABI) showed 1.17/1.15 (right/left), which is within normal limit [9]. The detailed results of PWV were that L (127) = L1(65) + L2(34) + L3(28), PEP 106, ET 251, R-AI 1.65 and PEP/ET 0.44. These data obtained this time were in the normal range.

Figure 1: Results of Pulse Wave Velocity (PWV)

The related function showed unremarkable.

Figure 2: Evaluation of Vascular age by PWV

It shows arteriosclerosis for 60s.

Figure 3: Abdominal CT scan

1. fatty liver is observed.

2. unremarkable gall bladder

Blood Chemistry and Clinical Progress

The results of blood biochemistry associated with clinical progress and treatment are summarized in Figure 4. Three sections, A, B, and C, are described in the following.

A) T2D (yellow): Diabetic control was exacerbated in the autumn 2021, with HbA1c rising to 7.7%. This coincided with the starting for the clinical application of imeglimin (Twymeeg) in Japan. Therefore, Twymeeg 2000 mg/day was initiated. After that, HbA1c improved to 6.8% in 4 months and then stabilized about 6.2-6.5%.

B) Anemia (cyan): The patient previously had hemorrhoids. In February 2023, the patient was asymptomatic and was found to be anemic as Hb 7.9 g/dL and MCV 73 fL. He immediately underwent surgical treatment and began taking Sodium Ferrous Citrate. The patient's condition remained stable until October 2025, when he experienced heavy bleeding from hemorrhoids and developed anemia with a hemoglobin level of 7.4 g/dL. He was hospitalized and underwent surgical treatment. During this episode, his MCV remained within the normal range at 90.2 fL.

C) Dyslipidemia (green): His liver and renal function had not shown any significant changes. Regarding lipids, his LDL level rose to 159 mg/dL in spring 2022. Then, he was initiated on rosuvastatin 2.5 mg. Since then, his LDL level has remained at a level of 51-63 mg/dL.

Figure 4: Clinical progress of biochemistry and treatment

A: diabetic situation by imeglimin

B: bleeding episode, anemia and treatment

C: improvement of LDL value for years

Ethical standards

This report is complied with Helsinki Declaration [10]. Some commentary showed the protection for personal right. The principle has ethic rule for medical research in human subjects. Necessary guideline is from Ministry of Education, Culture, Sports, Science Technology and Ministry of Health, Labour and Welfare. The authors and collaborators set up ethical committee in Sakamoto Hospital, that included the president, internists, surgeon, nurse, dietitian, pharmacist and legal professional. They discussed satisfactory about current case, agreed the protocol and took informed consent from the case.

Discussion

Current case showed several characteristic aspects in the light of clinical problems of multiple departments in the hospital. He has been treated in the department of internal medicine, surgery, neurosurgery and orthopedics. For various history and treatments, his medical problems and related medicine can be summarized in the followings.

#1 type 2 diabetes (T2D): imeglimin (Twymeeg) 2000mg, metformin 500mg, Linagliptin (Trazenta) as DPP4-i, Empagliflozin 10mg (Jardiance) as SGLT2-i, and continuing LCD as basic nutritional treatment [11].

#2 hypertension: Telmisartan 40mg as Angiotensin II Receptor Blocker (ARB), Cilnidipine 10mg as Calcium Channel Blocker (CCB).

#3 dyslipidemia: rosuvastatin 2.5mg.

#4 hemorrhoidal bleeding: Sodium Ferrous Citrate 50mg.

#5 CVA: Edoxaban tosilate hydrate ?Lixiana? 60mg. It has been given due to possible existence of cerebral vascular accident (CVA) for years.

#6 COPD: Indacaterol maleate, glycopyrronium bromide (Ultibro) was provided. It was because of chronic obstructive pulmonary disease (COPD).

#7 LBP: Tramadol and Acetoaminophen, plus Pregabalin (Lyrica). He has low back pain (LBP) for long, and then he has continued to take Tramcet combination tablets and Lyrica 150mg /day.

#8 GERD: Esomeprazole (Nexium) 20mg and Magnesium Oxide (Magmitt Tablets) 990mg/day. These meds are given because he has Gastroesophageal Reflux Disease (GERD) for long.

This patient was able to continue super-LCD for long, after fully understanding as effective dietary therapy [12]. As a result, he could lose sufficient weight, and his BMI dropped from 34.8 to 30.1 kg/m². Clinical efficacy of LCD was presented by the evidence of Dietary Intervention Randomized Controlled Trial (DIRECT), and successive research [13,14]. There are three types of LCDs, which are super LCD, standard LCD, and petit LCD, where carbohydrate percentages are 12%, 26%, and 40%, respectively [15,16]. Thus, the basis for his diabetic improvement would be actual continuation of LCD.

For pharmacotherapy of T2D in this case, metformin and imeglimin were provided twice a day (BID) [17]. The difference of Metformin was studied for once-daily vs twice-daily of Metformin [18]. As a result, no differences of HbA1c reduction was found between the both groups. Another investigation was conducted for Once/Twice Daily vs Immediate-Release of metformin [19]. The results showed similar HbA1c response was observed for these groups.

In the case of imeglimin, standard administration method has been twice daily (BID) [20]. For clinical study of imeglimin, Trials of IMeglimin for Efficacy and Safety (TIMES) 1,2 and also 3 have been known. In TIMES 1, 1000 mg BID vs Placebo was compared in the research of Japan [21]. Some large studies were conducted for the comparison of BID 1000mg or 1500mg twice daily [22]. Currently, no large-scale randomized trials comparing once-daily and twice-daily imeglimin have been identified in the international current status of imeglimin dosage frequency. Furthermore, clinical focus includes long period of administration of imeglimin (Twymeeg) associated with various investigation during clinical course [23]. It has been recognized to present effect and safely for T2D patients.

Some limitation may be present in this article. This case has several specific problems, including occasional episode of hemorrhoidal bleeding and anemia. In addition, he has other complications of obesity, Met-S, leading to arteriosclerosis. The case is required to be followed up with attention.

In summary, 56-year-old male was described for his characteristic general progress associated with related perspectives. He presented several medical problems, that will be further studied leading to the development of clinical research.

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

Funding: There was no funding received for this paper.

International Journal of Case Reports and Clinical Images