Improved Glucose Variability in Elderly Case of Type 2 Diabetes (T2D) With Retinopathy by Vildagliptin/Metformin (Equmet)

Bando H, Kato Y, Yamashita H, Ikezoe M, Fukushima N, Kawahito A, Sueki E, Aihara A, Fujii F and Kanazawa S

Published on: 2024-10-17

Abstract

The case is 81-year-old male with type 2 diabetes (T2D) and cataract as mild simple retinopathy. He has T2D for 14 years, and HbA1c was increased to 9.4% in October 2003. His medication was changed from vildagliptin/metformin (EquMet LD) to EquMet HD with metformin 1000mg/day. The HbA1c was gradually and apparently decreased to 7.3% in 6 months. This combined oral hypoglycemic agent (OHA) has characteristic benefits for twice administration, controlling glucose control for all day, and stabilizing retinopathy. He continued petite low carbohydrate diet (petite LCD) that is most mild carbohydrate restriction, according to Japan LCD promotion Association (JLCDPA).

Keywords

Petite low carbohydrate diet (petite LCD); Vildagliptin/Metformin (EquMet); Japan LCD promotion Association (JLCDPA); Oral hypoglycemic agents (OHAs); Mean amplitude of glucose excursions (MAGE)

Introduction

Regarding type 2 diabetes (T2D), fundamental treatment principle has been known as diet therapy, exercise and pharmacotherapy for long [1]. In the light of history of diabetic therapeutic measures, calorie restriction (CR) was almost standard formerly, but after that low carbohydrate diet (LCD) was proposed by famous doctors of Bernstein and Atkins [2,3]. Successively, LCD has attracted attention in medical and health care fields, and clinical benefit of LCD has attracted attention so far [4]. On the other hand, authors and co-researchers have initiated LCD in Japan, and developed LCD medically and also socially through Japan LCD promotion association (JLCDPA) [5]. We have proposed three useful patterns of LCD, which are petite-LCD, standard-LCD and super-LCD [6]. Each style has carbohydrate including ratio as 40%, 26% and 12%, respectively, and adequate educational seminars have been developed [7,8].

From diabetic treatment point of oral hypoglycemic agents (OHAs), several kinds of novel medicine were developed in these days [9]. Among them, metformin has been the first-line OHA and it was used for long years across the world [10]. Dipeptidyl peptidase-4 inhibitors (DPP-4i) has been widely used for its safety and effectiveness, especially in Japan and Asian countries [11]. From these clinical situations, some OHAs have been administered by the combined tablets for useful prescription. The combination of two agents for vildagliptin/metformin (EquMet) are widely prescribed for its clinical efficacy of improving diabetic states [12].

Authors et al. have continued diabetic research until now, and presented several reports about T2D and OHAs [13,14]. We have recently encountered a T2D elderly male case with T2D and mild retionopathy treated by EquMet. General clinical progress with some perspectives are described in this article.

Presentation of Cases

History and Physicals

Current case is 81-year-old male with T2D. As his past history, he was diagnosed as mild T2D about 14 years ago, and has been treated for some oral hypoglycemic agents (OHAs). During 2022 to summer 2023, his HbA1c was around 8%, and increased to 9.4% in October 2023.

His physical examination showed as follows: consciousness, conversation, and general movements were normal. Vitals signs were unremarkable with BP 126/66, pulse 66/min and SpO2 98%. His head, face, heart, lung, abdomen and neurological exams were negative. His physique revealed height 162cm, weight 70.7kg, and BMI 26.9 kg/m².

Exams and Clinical Progress

The electrocardiogram (ECG) revealed within normal limits (WNL) and chest X-ray was negative. The biochemistry tests for consecutive 3 data were summarized in Table 1, in which liver, renal, lipids and CBC were negative.

Table 1: Changes in laboratory Data.

		2023	2023	2024	Units
		Mar	Sep	Mar	Units
Liver	AST	32	36	30	(U/L)
	ALT	25	29	23	(U/L)
	GGT	30	42	23	(U/L)
Renal	UA	6.3	5.9	6.6	(mg/dL)
	BUN	13	11	19	(mg/dL)
	Cre	1.05	1.02	1.01	(mg/dL)
Lipids	HDL	42	44	39	(mg/dL)
	LDL	109	115	107	(mg/dL)
	TG	189	188	153	(mg/dL)
CBC	WBC	61	55	54	(x10*2/μL)
	RBC	522	506	490	(x10*4/μL)
	Hb	14.7	14.3	13.6	(g/dL)
	PLT	19.7	19.0	18.4	(x10*4/μL)

As he showed higher HbA1c, we changed the prescription from EquMet LD to EquMet HD (Figure 1). It includes vildagliptin 50mg and Metformin 500mg in a tablet, and it is administered twice a day. After that, he showed gradual improvement, in which HbA1c was decreased to 7.3% for 6 months. During the clinical progress, he has continued to take several medicines of ipragliflozin L-proline, glimepiride and tamsulosin for T2D and benign prostate hypertrophy (BPH).

Figure 1: Clinical Course of the Case with HbA1c and Medication.

During his clinical progress, he did not show any symptoms or signs of gastro-intestinal adverse effects (GI-AE). He can tolerate well the current treatment, and no other problems were clinically observed.

Ethical Standards

Current article is complied with the ethical guideline of Declaration of Helsinki [15]. In addition, some comments are with the protection regulation. The principle was accompanied with ethic regulation for clinical research and practice. This guideline has been found in Japanese Ministry, including the Ministry of Education, Culture, Sports, Science Technology (MEXT) and the Ministry of Health, Labor and Welfare (MHLW) in Japan.

The authors et al. set up the ethical committee in our hospital. It included hospital president, physicians, registered nurse, pharmacist, nutritionist, and legal professional. These members have discussed enough the current protocol and agreed. The informed consent was taken from the current case by the document.

Discussion

Concerning the current elderly case, some medical problems can be summarized. He had the onset of T2D 14 years ago, and benign prostatic hyperplasia (BPH) 8 years ago, and he has been taking medication for two diseases [16]. Other clinical problems suggest dyslipidemia. In latest 3 blood chemistry, LDL and HDL values were within the normal range, and TG was slightly high, in which this may be due to blood sampling after meals.

Furthermore, he was pointed out to have mild cataracts 12 years ago, and ophthalmic progress has been observed until now [17]. He has been recently checked every three months, and right eye seems to be a little develop.

Currently, he has bilateral cataract and the early stage of simple diabetic retinopathy. As the data of January 2024, the findings were RV=0.3p(n,c.), LV=0.8(n,c.), RT=13.0, LT=11.7. In detail, the posterior subcapsular opacity of the right eye becomes a little stronger. A few pinpoint hemorrhages were noted on the fundus. Surgery on the right side may be scheduled in the future, by observing its progress and patient's daily life situation and wishes [18]. Pirenoxine ophthalmic suspension has been prescribed for treatment. From mentioned above, the medical problems in this case can be summarized as 1) T2D, 2) BPH, 3) probable dyslipidemia, 4) bilateral cataract, 5) diabetic retinopathy.

As to clinical progress treated by vildagliptin/metformin (EquMet HD), remarkable effect was found [19]. HbA1c was gradually and apparently decreased 1.6% for 6 months. It is likely to be slow and apparent clinical efficacy. He is elderly case, and he was advised to continue petite low carbohydrate diet (LCD). He regularly took rice and certain amount of carbohydrate in the supper. In such case, EquMet seems to be beneficial for controlling glucose variability. The reason would be that vildagliptin/metformin is administered twice a day, and it can present smaller mean amplitude of glycemic excursions (MAGE) [20]. When vildagliptin is provided at night, the glucose elevation can be decreased during midnight to morning. Such mechanism can lead to the improvement of glucose variability.

This case showed cataract as the early stage of simple retinopathy. He did not show apparent neuropathy or nephropathy as microangiopathy. For diabetic macroangiopathy, protection of developing exacerbation would be important. Early treatment by vildagliptin/metformin (EquMet) has brought satisfactory decrease for risk degree of macrovascular events [12,21]. It was presented by the sub-analysis of VERIFY studies. They stand for the investigations of vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY) [12,21]. From VERIFY data, there were two groups of young T2D and late-onset T2D. The end point in the protocol was the time of treatment failure, in which HbA1c was elevated to 7.0%. The results showed that the risk was 48% vs 46% for each group associated with significant difference [22]. Thus, treatment-naïve young T2D patients has presented the improvement of earlier durability and later exacerbation for glucose control situation.

Regarding nutritional therapy, petite LCD has been applied for the case, which seemed to be adequate for aged case and his regular meal pattern. Historically, compared results were shown for LCD, CR and Mediterranean Diet (MD) by the report of Dietary Intervention Randomized Controlled Trial (DIRECT) Group. LCD seems to be effective in short period, but the continuing process is not so easy. Then, the combined therapeutic idea has been observed of LCD and MD, in which LCD is started followed by MD after that [1]. Further, MD and also Paleolithic diet are compared for several benefits [23]. Future combination of diet measures will be in focus for successful diet treatment [24,25].

Certain limitations may be present in this article. It is only one case report, and he showed improvement of diabetic variability and stable retinopathy. He did not have apparent macroangiopathy so far, but we will pay attention to the aggravation of diabetic complication. The principle of diabetic treatment would be the protection of Atherosclerotic Cardiovascular Disease (ASCVD).

In summary, 81-year-old male with T2D and retinopathy was shown associated with related perspectives. Clinical progress would be followed with attention for refraining from development of diabetic complications. Current report becomes hopefully a useful reference for adequate diabetic care.

Conflict of interest

The authors declare no conflict of interest.

Funding

There was no funding received for this paper.

Journal of Medical and Clinical Studies