Around the world, the average life expectancy has been increasing in developing and developed countries. [1]. From medical, economic and social points of view, Japan has kept satisfactory degree of them, and then the elderly population has been increasing [2]. Consequently, many elderly people visit medical institutions who have often hypertension, type 2 diabetes (T2D), obesity and metabolic syndrome (Met-S) [3]. Authors and clinical team have treated lots of patients with Met-S and lifestyle-related disease for years. As fundamental nutritional treatment, adequate diet therapy seems to be required. They include formerly calorie restriction (CR), and recently low carbohydrate diet (LCD) [4]. LCD was firstly initiated by authors et al. and successively LCD became more understood for decades [5]. We have developed LCD by workshops, textbooks and medical associations through Japan LCD promotion association (JLCDPA) [6].

In the aged society, elderly patients tend to have lifestyle-related disease and related complications and comorbidities [6]. They include diabetic microangiopathy and macroangiopathy, associated with other impaired function situation [7]. During usual out-clinic, our diagnosis and treatment should include adequate management according to various situation for each patient. In particular, elderly male in their 70s and 80s are more likely to develop urinary problems from BPH [8]. As a matter of fact, they has often some symptoms and signs of lower urinary tract symptoms (LUTS) or overactive bladder (OAB).

Authors et al. have been involved in clinical practice and research for years, especially in the field of lifestyle-related disease, diabetes, obesity, atherosclerotic cardiovascular disease (ASCVD) and others [9,10]. Regarding our out-clinic situation, we always pay attention from primary care, holistic medicine and bio-psycho-social medicine points of view [11]. As a specific method in the out-clinic, we try deep communication with patient, related family, doctor and also nurse in out-clinic. In such situation, we have experienced a meaningful elderly male case with T2D and BPH. In this article, his general clinical progress and related perspectives will be shown and discussed.

Medical History

The patient is 72-year-old male who was treated by BPH in the urology clinic nearby for years. He was also treated T2D, but glucose control was not good, and then introduced to our diabetic department for further evaluation and better treatment. He visited us in August 2025, and HbA1c was 7.9% and 58.3kg in weight. Our diabetic team has checked him up in precise manner, communicated in detail. We educated him the importance of LCD and started imeglimin (Twymeeg). His general clinical progress is summarized in Figure 1.

Figure 1: Clinical progress of the case.

Physicals and Some Exams

Physical examination in August 2025 showed as follows: consciousness, speech mode and conversation were normal, and his vital signs were unremarkable as BP 130/76 mmHg, pulse 76, SpO2 98%. No changes were observed in the head, face, neck, heart, lung, abdomen, extremities or neurological tests.

Clinical progress of blood chemistry is summarized in Figure 2. The results include in June 2025 from previous clinic, and November 2025 that is 3 months after imeglimin administration. General data of liver, renal lipids and complete blood count (CBC) showed normal ranges. Chest X-P revealed negative examination, and Electrocardiogram (ECG) showed pulse 82/min, ordinary sinus rhythm (OSR), regular, without remarkable specific ST-T changes.

Figure 2: Progress in blood chemistry.

Clinical Progress

 After evaluation of detailed situation and diagnosis, LCD was immediately started as nutritional therapy. We asked him to what extent he can continue restrict carbohydrate intake. Actual LCD include three practical types, which are super-LCD, standard-LCD and petite-LCD with carbohydrate involvement ratio as 12%, 26%, and 40%, respectively [12]. It was decided that he will start from super-LCD, and try to continue super- or standard-LCD for long. He showed improvement of HbA1c and body weight for 2 months. Then, he hoped to take some amount of carbohydrate, and then voglibose was added for suppress post-prandial hyperglycemia. He showed remarkable clinical effect as -0.9% of HbA1c and -4.5kg of weight for 3 months (Figure 2). After that, he can continue the similar lifestyle.

Ethical Standards

 This paper was complied with the Helsinki Declaration [13]. Certain commentary revealed the protection for person right. The principle shows the ethical rule of human subjects for clinical research. Required guideline was from the Ministry of Education, Culture, Sports, Science Technology and the Ministry of Health, Labour and Welfare. Authors et al. has set up the ethical committee in Kanaiso Hospital, including president, doctor, nurse, pharmacist, nutritionist and legal professional. We discussed the protocol satisfactory, agreed the content, and took the informed consent from the patient.

Current case has several medical problems, which are i) T2D, ii) imeglimin (Twymeeg) for Treatment of T2D, iii) benign prostatic hyperplasia (BPH) with symptoms of lower urinary tract symptoms (LUTS? and overactive bladder (OAB), iv) naftopidil as an α₁-adrenoceptor antagonist, v) blood pressure situation and GI-AE from naftopidil, and vi) other possible clinical problems related to these issues. Some perspectives are described in the following.

For clinical effect of imeglimin, he showed significant reduction of HbA1c and body weight for short period. When starting imeglimin, we explained the importance and efficacy of LCD in the basic lifestyle. He can continue LCD for 1-2 months, but he felt rather difficulty for restricting carbohydrate [14]. According to the situation, we added voglibose by pre-prandial administration. Subsequently, HbA1c value was decreased more. Imeglimin has international large muti-center study, that is Trials of IMeglimin for Efficacy and Safety (TIMES) [15]. In TIMES 2 study, clinical effects of combined treatment of OHAs were reported [16]. They showed that 0.46% in monotherapy, 0.67% in biguanide, 0.92% in DPP4-i, and 0.85% in α-glucosidase inhibitor (α-GI). Consequently, remarkable effect was likely found from LCD, imeglimin, LCD and good communication to patient [17].

T2D and LUTS/OAB have certain relationship from autonomic neuropathy, leading to detrusor dysfunction and impaired bladder sensation. Then diabetic patients often have mixed urine symptoms for voiding and storage mechanism. From several studies, naftopidil can improve storage and voiding symptoms, suggesting beneficial mechanism beyond simple smooth muscle relaxation of the prostate [18]. Such effects are particularly relevant in T2D patients, where neurogenic components play a substantial role in LUTS. Although direct evidence in diabetic populations remains limited, these pharmacological characteristics support the potential utility of naftopidil.

OAB symptoms are highly observed in T2D due to the altered bladder sensation and detrusor overactivity. By comparative studies, naftopidil may give greater improvement in storage symptoms than highly α-A-selective agents [19]. It would be clinically meaningful, as anticholinergic agents are often poorly tolerated in T2D. It is due to adverse effects such as constipation, dry mouth, and possible cognitive impairment. Therefore, naftopidil may represent a reasonable therapeutic option for T2D with BPH, LUTS and OAB [20]. It is particularly beneficial when anticholinergic therapy would be contraindicated or poorly tolerated.

Concerning blood pressure, this case showed normal range of BP. Naftopidil is an α₁-adrenoceptor antagonist, which has potential to lower BP through vasodilation [21]. However, compared with other α₁-blockers, its pressure–lowering effect seems to be modest. From previous reports, α₁-blockers in T2D cases showed effective BP reduction without significant deterioration of glucose metabolism for fasting plasma glucose (FPG) and HbA1c. This case has not felt dizziness or orthostatic hypotension. T2D cases may have autonomic dysfunction and increased risk of orthostatic hypotension, and naftopidil may bring these cardiovascular episode. We have to follow possible cardiovascular symptoms when initiating naftopidil in diabetic patients.

T2D patients often develop OAB as decreasing quality of life (QOL). In the latest report, T2D cases aged >55 years (n=289) showed OAB for 24%, and only 32% cases with OHA symptom received relevant pharmacological treatment [22]. Diabetologists have to pay attention to these evidence and usual management for elderly male.

Several limitation should be acknowledged. This case showed remarkable improvement for HbA1c and weight, in which some additional factors may be involved. He has continued naftopidil due to BPH with LUTS and OAB, and naftopidil may influence the clinical progress of the improvement and exacerbation of T2D [23]. This case has rather short history of diabetes, and the diabetic degree is not so heavy level. We will follow up the future course with careful attention.

In summary, 72-year-old male patient with T2D and BPH treated by imeglimin and naftopidil was presented. The perspectives included relationship among T2D, BPH, LUTS/OAB, naftopidil, LCD, BP, adverse effects and mutual influences. It is expected that diabetes-specific investigations would be expected associated with other related matters for future clinical practice and research.

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

Funding: There was no funding received for this paper.

1. Tripathi SS, Singh BK. Chapter 15 - Interplay between diet, exercise, and intermittent fasting in metabolic disease reduction in people with obesity and promoting healthy aging. Eds: Singh AK, Sinha JK, Seetharam RN. The Potential of Intermittent Fasting in Age-related Diseases and Precision Antiaging Therapeutics. Academic Press. 2026; 319-332.
2. Lim LL, Khunti K. Global inequality in target attainment among people with diabetes. Lancet Glob Health. 2026; 14: e2-e3.
3. American Diabetes Association Professional Practice Committee for Diabetes*; 8. Obesity and Weight Management for the Prevention and Treatment of Diabetes: Standards of Care in Diabetes–2026. Diabetes Care1 January 2026; 49: S166-S182. 
4. Ebe K, Wood M and Bando H. In Memory of Dr. Richard K. Bernstein, April 17. Int J Endocrinol Diabetes. 2025; 8: 188.
5. Wood M, Bando H and Ebe K. Immune Function Augmentation in Low-Carbohydrate Diet (LCD). Int J Endocrinol Diabetes. 2025; 8: 186.
6. Bando H, Okada M, Ogawa T, Iwatsuki N and Sakamoto K. Multiple Arteriosclerosis with Type 2 Diabetes (T2D) Treated By Imeglimin (Twymeeg). Int J Endocrinol Diabetes. 2026; 9: 200.
7. Lu Z, An N, Sheng S, Hong M, Deng P, Wu J, et al. Machine learning combining external validation to explore the immunopathogenesis of diabetic foot ulcer and predict therapeutic drugs. PLoS One. 2025; 20: e0328906.
8. Akhtar OS, Singh V, Bhojani KA, Dharmadhikari S, Bhargave C, Mane A, et al. A Comprehensive Review of the Clinical Evidence on the Efficacy, Effectiveness, and Safety of Silodosin for the Treatment of Benign Prostatic Hyperplasia. Cureus. 2025; 17: e85445.
9. Kawahito A, Sueki E, Aihara A, Ikezoe M, Fukushima N, Matsushima K, et al. Remarkable Reduction of HbA1c and Weight by Low Carbohydrate Diet (LCD) and Imeglimin (Twymeeg) in a Diabetic Male. Int J Endocrinol Diabetes. 2026; 9: 201.
10. Bando H, Iwatsuki N, Okada M, Ogawa T and Sakamoto K. A Diabetic Male with Close Relationship of Hba1c and Average Glucose (AG) During Treatment of Imeglimin (Twymeeg). J Med Clin Stud. 2026; 9: 238.
11. Uchida Y, Bando H, Nishikiori Y, Bando M and Yoshioka A. Assertive Thinking May Bring Beneficial Human Relationship in The Light of Psychosomatic Medicine and Hinohara-Ism. Int J Case Rep Clin Image. 2025; 7: 244.
12. 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.
13. 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: 14-18.
14. Kusumoto T, Bando H, Hayashi K, Yasuoka E, Shibata M, Takagishi H. Actual Meal of Low Carbohydrate Diet (LCD) for Diabetic Patient Treated by Effective Imeglimin (Twymeeg). Asp Biomed Clin Case Rep. 2023; 6: 178-185.
15. 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.
16. 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.
17. 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: 191.
18. Masumori N. Naftopidil for the treatment of urinary symptoms in patients with benign prostatic hyperplasia. Ther Clin Risk Manag. 2011; 7: 227-238.
19. Takahashi S, Tajima A, Matsushima H, Kawamura T, Tominaga T, Kitamura T. Clinical efficacy of an alpha1A/D-adrenoceptor blocker (naftopidil) on overactive bladder symptoms in patients with benign prostatic hyperplasia. Int J Urol. 2006; 13:15-20.
20. Tanuma Y, Tanaka Y, Takeyama K, Okamoto T. The predictive factors of α1-D/A adrenoceptor antagonist, naftopidil, dose increase therapy for male lower urinary tract symptoms caused by benign prostatic hyperplasia: INFORM study. Urol Ann. 2017; 9: 261-267.
21. Maruyama H, Saruta T, Itoh H, Koyama K, Kido K, Itoh K, et al. Effect of alpha-adrenergic blockade on blood pressure, glucose, and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus. Am Heart J. 1991; 121: 1302-1306.
22. Ito H, Watanabe E, Tanaka M, Matsumoto S, Inoue H, Antoku S, et al. Prevalence and Associated Factors of Overactive Bladder in Japanese Patients with Type 2 Diabetes. Geriatr Gerontol Int. 2025.
23. Sahu S, Minj P, Dewangan D, Saraf S, Tirkey R. Novel Compounds in Targeting the α1-adrenoceptor for Antihypertensive Therapy. Cardiovasc Hematol Agents Med Chem. 2025.