The world's first report that SGLT2 inhibitors are effective for carpal tunnel syndrome in patients with diabetes
Carpal tunnel syndrome treated by SGLT2 inhibitor

Carpal tunnel syndrome (hereinafter abbreviated as CTS) is a strangulation neuropathy of the median nerve whose pathological condition is sensory deficits and motor deficits in the median nerve innervation region. Perceptual deficits are primarily characterized by tiredness on the thumb, index, middle and radial sides of the thumb and tingling pain. On the other hand, movement disorders are mainly the palmar abduction and confrontational movement of the thumb. CTS is the most common type of strangulation neuropathy and has a high prevalence in diabetics.
Diabetes is recognized as one of the risk factors for carpal tunnel syndrome. As a result of a large-scale study, it has been reported that the risk rate of diabetic patients is 1.51 times higher than that of non-diabetic patients 1). There are many bilateral cases, and it is known that the onset is more likely to occur with aging and weight gain.
In CTS associated with diabetes, it is said that demyelination and axonal degeneration occur at a high rate in the median nerve at the time of clinical neuropathy onset, which makes diagnosis and treatment difficult. In general, females have a higher prevalence than males, and by age group, males are often 45 to 54 years old, and females are known to develop a wide range of 35 to 64 years old. At our hospital, we experienced a woman who showed a marked improvement in CTS and decided to report it at an academic conference. This is the first report in the world in the literature.

It has been reported that the prevalence of CTS associated with diabetes ranges from 10 to 30%, and the prevalence of CTS without symptoms is 22%, which is twice the prevalence of CTS with symptoms (11%) 2). .. It has been reported that CTS is associated with about 30% in the case of diabetic polyneuritis, but is halved in the absence of it 1). Thus, in diabetes clinics, CTS is a frequently encountered disorder. Its diagnosis and treatment was primarily under the guidance of an orthopedic surgeon. In addition, it is said that there is no Gold-standard for the diagnosis of CTS. There is no gold standard as to how the best method for doctors to combine interviews, physical findings, and electrophysiological tests (nerve conduction velocity, etc.) for subjective symptoms associated with CTS is comprehensive. Judgment is prioritized. The electrophysiological examination is not necessarily regarded as a necessary examination for diagnosis in the guidelines of the American Orthopedic Association 3).
Patients who responded significantly to SGLT2 inhibitors at our hospital did not have a distal latency extension of nerve conduction velocity, but had Tinel's sign and a positive Phalen test, and multiple orthopedic specialists confirmed CTS. He was diagnosed and recommended surgery. The authors have not reported any cases in which CTS was dramatically improved by taking SGLT2 inhibitors in patients with such a condition.

In normal CTS, there is consensus that an increase in volume of structures around the median nerve (flexor tendon, synovium, etc.) in the carpal tunnel exists as a background cause. Therefore, it is easy to understand that the mechanism by which SGLT2 inhibitor is taken and the CTS is improved is an event mediated by the mechanism of decrease in body fluid water content and is interpreted as a decrease in the volume of the above-mentioned structure. CTS is known to be more likely to occur with pregnancy, especially with edema associated with pregnancy. Atsugi et al. Also reported a case in which systemic edema was observed after cesarean section and CTS developed from the day after surgery, but CTS was improved by administration of furosemide 4).
In diabetes, diuretics such as furosemide tend to be avoided from treatment options because they worsen glycemic control. Conversely, pioglitazone is prone to edema. Insulin secreted from the pancreas by insulin preparations, SU agents, DPP4 inhibitors, etc. is also known to increase body weight by increasing sodium reabsorption in the kidneys. Insulin edema may occur when blood sugar is controlled rapidly. Therefore, it cannot be denied that the conventional treatment for diabetes often tends to increase the plasma volume in the body, which may be correlated with the phenomenon that the frequency of complication of CTS in diabetes is high.
Furthermore, on the other hand, we (Kameyama et al.) Should administer prednisolone (10 to 20 mg) for a limited time to patients with severe hand flexor tendon synovitis due to CTS and complaints of finger pain and limited range of motion. 5). However, oral prednisolone treatment poses a risk of worsening glycemic control in diabetic patients, which is a clinical obstacle.
Under these circumstances, if an SGLT2 inhibitor can help a diabetes treatment selection drug and create a state in which blood glucose can be controlled while reducing the circulating plasma volume of body fluids, it can be an epoch-making treatment method. .. This report suggests that SGLT2 inhibitors will be tried as one of the treatment options for CTS in diabetic patients in the future.
In general, it is reported that about 50% of CTSs in pregnancy also have a delay in nerve conduction velocity 6). No delay was observed in this case either. In that sense, it is inferred that the disorder in this case may have been a mild disorder even in CTS. Therefore, in severe CTS that does not improve even if SGLT2 inhibitor is administered, indications such as surgery will still remain.
In addition, we examined the shape of the median nerve in CTS patients by ultrasonic echo, and monitored the cross-sectional area and flatness of the median nerve before and after treatment at the carpal tunnel level in the field of hand surgery, and clinical symptoms and median nerve disconnection. It is reported that the area correlates 5). In the future, it is expected that more objective results will be found by monitoring and comparing the carpal tunnel level before and after SGLT2 administration.

Conclusion

With the advent of SGLT2 inhibitors, diabetic patients will have more opportunities to reduce fluid volume. In that case, it can be easily inferred that the SGLT2 inhibitor contributes to the improvement of treatment in various diseases that have been conventionally considered to be exacerbated by an increase in body fluid volume. Overseas, SGLT2 inhibitors have been shown to be particularly effective in improving heart failure while taking pioglitazone7), but this is the first report in the world of diseases such as CTS. In the future, when a patient with CTS is examined in diabetes, it is important to administer an SGLT2 inhibitor, observe the transition of symptoms, and consider it as an aid to treatment.

Citations
1) Toshihiko Imaeda. Epidemiology of carpal tunnel syndrome. MB Orthop. 20: 1-7, 2002
2) Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O'Brien PC, Melton LJ 3rd, Service FJ.The prevalence of staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology 43: 817-824, 1993
3) Keith MW, Masear V, Chung K, et al .: Diagnosis of carpal tunnel syndrome. J Am Acad Orthop Surg 17: 389-396, 2009
4) Toshiaki Atsugi, Noboru Saeki, Hiroshi Hamada, Masashi Kawamoto. A case of carpal tunnel syndrome that developed after cesarean section. Anesthesia and resuscitation. 46: 45-47, 2010
5) Makoto Kameyama. Carpal tunnel syndrome in diabetics. Diabetic complications 27: 169-172, 2013
6) Shinichiro Takayama, Kenichiro Uchinishi, Shonosuke Iijima: About carpal tunnel syndrome related to pregnancy. Outside clinical orthopedics. 20: 1381-1386, 1985
7) Rosenstock J , Vico M , Wei L , Salsali A , List JF . Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care. 35 1473-8, 2012

Changes in eating habits after the start of SGLT2 inhibitors (reported at the Diabetes Kinki Regional Association in 2014)

We interviewed 168 outpatients with type 2 diabetes about their dietary habits after starting SGLT2 inhibitors. As a result, after 2 weeks, 20% were aware of the feeling of sugar depletion, and 29% wanted sugar and carbohydrates. 19% of patients began to eat more than before. When we re-examined six weeks later, the percentage of patients who continued to overeat was the same as 20%, and among them, many patients ate too much carbohydrates, sweets, and fruit madoka. On the other hand, the number of patients with decreased appetite increased to 9%. It was found that some patients tend to overeat due to the desire to take sugar due to the excretion of sugar, but on the other hand, 6 weeks after the start of SGLT2 inhibitor, the appetite may calm down. It turned out that there was. For patients with a feeling of sugar depletion, whether it is necessary to allow sugar intake or whether it is necessary to change the instruction table will be a controversial issue in the future.

Compensatory overeating (COE) could be a problem of diabetes diet education after sodium-glucose co-transporter 2 inhibitor treatment.

Background: Compensatory overeating (hereinafter referred to as COE) has been controversial issue for treatment of SGLT2i (sodium-glucose co-transporter 2 inhibitor). Among the out-patients of HDC Atlas clinic, we experienced high percentage of patients who suffered from COE after taking SGLT2i.
Method: 172 type 2 diabetes ambulatory patients were subjected. Male 133, female 39. Interview survey was conducted after 2 weeks and 6 weeks of STLT2i treatment start. Carbohydrate depletion feeling, trend of meal, and trend of overeating were investigated.
Result: After two weeks, carbohydrate depletion feeling occurs in 28%. Carbohydrate sense of loss occurs in 19%. After 6 weeks, 74% noticed the overeating of carbohydrate, sweets, and fruits. As for COE, after 2 weeks, 18% noticed COE, and after 6 weeks, 29% noticed COE. This suggests that COE is likely to increase as time goes by.
Conclusion: Theoretically, diabetes patients under SGLT2i therapy lose 300 – 400 kcal in urine. However, practically, patients become likely to take more foods, especially carbohydrate, sweets, and fruits. The data suggest persistent urinary glucose excretion induced by SGLT2i was accompanied by compensatory overeating (COE), which immunod the weight loss induced by SGLT2 inhibition. Therefore, COE could be a problem of diabetes diet education.

Balanoposthitis is more common in younger generations.

Background:
SGLT2i (sodium-glucose transporter 2 inhibitors) has been used in Japan since April, 2014. Four products of SGLTi have been released and widely prescribed. One is ipragliflozin, and the others are dapagliflozin, luseogliflozin, and tofogliflozin. In common, genital infection However, practically, the question what kind of patients are likely to be affected regarding balanitis has not been clarified. Therefore, we reported the adverse effect of balanitis through closed SNS service, called as TmDance, and also gathered the official drug information from eight pharmaceutical companies.

Methods: Methods:
About 200 patients of type 2 diabetes were subjected at our HDC Atlas Clinic. They were equally out-patients. Their complaints were questioned and each of adverse effect was reported through TmDance (closed SNS service). TmDance is one of social medical network system, Which composed of closed and secret communication system between medical doctors and medical representatives independently. Medical doctor reported adverse effects soon after he noticed the adverse effect by using copy & past from electronic chart to the dairy of TmDance. Throudh TmDance, medical representativeitives of pharmaceutical companies promptly noticed and could gather the adverse effect information as soon as possible.
In addition, by making use of TmDance, the occurrence of adverse effect, especially regarding balanitis, was collected from medical representatives. Data of adverse effect in Japan, especially of balanitis, were based on the description of drug information which has been reported every month from eight pharmaceutical companies.

Result:
According to the database of drug information, in ipargliflozin, totally 22 patients of balanitis were reported. (Less than 50 y / o: 12, 50-59 y / o: 4, 60-69 y / o: 3, 70-: 3). In dapagliflozin, totally 3 patients were reported. (less than 50 y / o: 0, 50-59 y / o: 1, 60-69 y / o: 1, 70-: 1). In luseogliflozin, totally 3 patients were reported. (less than 50 y / o: 3, 50-59 y / o: 0, 60-69 y / o: 0, 70-: 0). In tofogliflozin, totally 2 patients were reported. (less than 50 y / o: 3, 50-59 y / o: 0, 60-69 y / o: 0, 70-: 0). than 50 y / o: 1, 50-59 y / o: 0, 60-69 y / o: 0, 70-: 1). According to the result reported by TmDance from HDC Atlas clinic, in ipragliflozin, totally 5 patients of balanitis were reported. (less than 50 y / o: 3, 50-59 y / o: 0, 60-69 y / o: 1, 70-: 1). In dapagliflozin, none patients were reported. In luseogliflozin, 1 patients were reported. (less than 50 y / o: 1, 50-59 y / o: 4, 60-69 y / o: 3, 70-: 0). In tofogliflozin, totally 1 patient was reported. (less than 50 y / o: 1, 50-59 y / o: 4, 60-69 y / o: 3, 70-: 0). than 50 y / o: 0, 50-59 y / o: 4, 60-69 y / o: 3, 70-: 1). Thus, 7 (23%) out of 30 were reported from HDC Atlas clinic th rough closed SNS of TmDance. In total of Japan, 16 (54%) out of 30 were under 49 years of old. At HDC Atlas Clinic, 4 (57%) out of 7 were under 49 years of old. Interestingly, 7 ( 23%) out of 30 patients were reported through closed SNS of TmDance. It suggests that the closed SNS system of TmDance can be fully applied with high quality and accuracy for reporting the adverse effect in medical practice.

Conclusion;
Contrary to the prediction, the adverse effect of balanitis was frequently found in the patients who were under 49 years of old. It was possibly due to the high opportunity of sex intercourse during the younger period than older period. For instance, some patients were worried. 26 percentage of balanitis was reported through internet media of TmDance. Thus, closed SNS communication system such as TmDance will bring a lot of benefits on reporting adverse effect of new drugs like SGLT2i.

Reference: Reference:
Johnsson KM, et al. Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications. 2013 Sep-Oct; 27 (5): 479-84.
Home page of explanation of TmDance: www.iryoo.net
Login: https://www.tmdance.com/

Suzuki Y.

HIGH OCCURRENCE OF BALANITIS AS AN ADVERSE EFFECT CAUSED BY SGLT2 INHIBITORS IS FREQUENTLY FOUND IN THE YOUNG

GENERATIONS BELOW 50 YESRS OF OLD

Diabetes Research and Clinical Practice, Vol.106, S266-S267

Published in issue: November, 2014

The world's first hypothesis that SGLT2 inhibitors exacerbate skin disorders due to "yellow sand" was announced.

In Japan, recent report of ipragliflozin: one of sodium-glucose cotransporter-2 (SGLT2) inhibitors, indicates the highest number of adverse effect is with skin complication. Japan Diabetes Society published warning recommendation in June 2014. However, the incidence of skin complication. has not been reported at any institute.
At our clinic, ipragliflozin was prescribed towards 142 patients of type 2 diabetes (male 112, female 30, aged 61.8 + 10.0 y / o (Mean + SD)). They had taken ipragliflozin for more than 6 weeks and switched to luseogliflozin, otherwise they had dropped out because of adverse effects. With them, the adverse effects were retrospectively examined.
In result, 22 patients dropped out, and 120 patients remained and switched ipragliflozin to luseogliflozin. Skin complication occurred in 19 patients (13.4%). Three patients experienced severe eruption. Regarding mild complication of skin, it had two different patterns. One is eruption with itching and the other is only itching. In result, 14 patients first noticed mild skin complication after ipragliflozin. 5 cases showed eruption only in ipragliflozin and dropped out. 7 cases showed itching only in ipragliflozin. The itching relieved after switching. 2 cases showed Other 2 patients noticed only after luseogliflozin but not after ipragliflozin. They switched back to ipragliflozin.
The true reason why skin complication is so highly found in patients with ipragliflozine after the release has not been clarified. One reason might be that the itching is so mild as not have been unnoticed in pre-launched clinical trials. And the other reason might be explained by that intra-tissue concentration ratio after 24 hours of medication (in plasma vs. in skin) is almost 6.5 times higher in rat with ipragliflozin than that with luseogliflozin (ipragliflozin; plasma: 6 ng eq / mL, skin: 15 ng eq / mL, ratio 2.5. vs. luseogliflozin; plasma: 6.92 ng eq / mL, skin: 2.72 ng eq / mL, ratio: 0.39) 2-3. This high intra-skin concentration ratio could lead to skin complication.
Environmental air change by Asian dust has been emerging problem recently in Japanese. Therefore, it might have become a latent trigger to immune disturbance, leading to skin complication. It could explain why the same trouble was not occurred during the phase 3 trial period of ipragliflozin when the problem of Asian dust was not serious in Japan .. To confirm these, more long time safety study should be needed.

References

1. 1. Japan Diabetes Society: Recommendation from "Committee on the proper use of SGLT2 inhibitors" (in Japanese) http://www.jds.or.jp/modules/important/index.php?page=article&storyid=48

2. Interview Form of ipragliflozin. Http://www.info.pmda.go.jp/go/interview/1/800126_3969018F1022_1_1F

2014. p73 (in Japanese)
3. Interview Form of luseogliflozin; http://www.info.pmda.go.jp/go/interview/1/400059_3969020F1020_1_001_1F
: 2014. p 61 (in Japanese)

1. Otani S 1, Onishi K , Mu H , Yokoyama Y , Hosoda T , Okamoto M , Kurozawa Y. The relationship between skin symptoms and allergic reactions to Asian dust. Int J Environ Res Public Health. 2012; 9: 4606-14.

2. 4. Kashiwagi A, Kazuta K, Goto K, Yoshida S, Ueyama E, Utsuno A. Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomised, double-blind, placebo-controlled study. Diabetes Obes Metab. 2014; 12. doi: 10.1111 / dom.12331

3. SKIN COMPLICATIONS OF SGLT2 INHIBITOR TRETMENT IN JAPANESE

   Diabetes Research and Clinical Practice, Vol.106, S265

   Published in issue: November, 2014

Ipragliflozin improves psoriasis and chronic eczema
Improvement of Psoriasis and Chronic eruption after taking SGLT2 inhibitor: ipragliflozin in diabetes of Japanese.

SGLT2 inhibitor (Sodium glucose transporter 2: SGLT2i) is medication to treat diabetes, being used all over the world. The pre-release clinical trials showed that SGLT2i affect few skin complication. However, after release of ipragliflozin, SGLT2i showed high incidence of skin complications in Japanese. The summary of ipragliflozin's adverse effect reported some severe cases. According to the condition, Japan Diabetes Society published a warning recommendation in June 2014, towards a proper usage of SGLT2i. 1).
At our clinic, seventeen patients were found who had eruption and / or itching after ipragliflozin treatment. Severe cases among them showed increased eosinophil and DLST (Drug-induced Lymphocyte Stimulation Test) was positive. Some cases noticed eruption and / or itching after taking one Or two tablets of ipragliflozine. Other cases noticed the symptoms after 10-30 days of taking ipragliflozine. The true pathogenesis has not been clarified.
Surprisingly, two patients were found whose skin disorder relieved after taking ipragliflozin. The episodes indicate that skin effect of ipragliflozin is not only harmful but also beneficial among individuals. Case 1: 67 y / o. Man. He had suffered from psoriasis for 4 years His symptoms abruptly relieved after taking ipragliflozin (Fig.1-a). The condition improved and became stable after two months. Case 2: 63 y / o. Man. He had suffered three years from chronic eruption 3). Over the years consultations with multiple dermatologists did not elicit a diagnosis, and symptoms did not improve after numerous trials of topical corticosteroids and systemic antihistamines. But, his symptom abruptly relieved after taking ipragliflozin (Fig. 1-b). The symptoms in the photo finally disappeared and he does not need topical medications. Thus, improvement of two different skin disorders was associated with taking ipragliflozin. The association in case 2 was distinct. Ipragliflozin might have an intra-skin-tissue effect possibly associated with immunologic factors 4).
In conclusion, although two cases episode is insufficient to determine the etiology and mechanism, they suggest a distinct association among ipragliflozin and skin function from a different point of view. The phenomena might give a new light in the treatment of psoriasis and chronic eruption of unknown etiology.

(/ 349 words)

References.

1. Japan Diabetes Society: Recommendation from "Committee on the proper use of SGLT2 inhibitors" (in Japanese) http://www.jds.or.jp/modules/important/index.php?page=article&storyid=48
2. Di Meglio P , Villanova F , Nestle FO . Psoriasis. Cold Spring Harb Perspect Med. 2014; 4. pii: a015354. Doi: 10.1101 / cshperspect.a015354.
3. Converse KD 1, Sturm JM , Slavin RG . Chronic bilateral pruritic arm dermatitis in a 61-year-old woman. Allergy Asthma Proc. 2013; 34: 558-61.
4. Wu JJ , Nguyen TU , Poon KY , Herrinton LJ . The association of psoriasis with autoimmune diseases. J Am Acad Dermatol. 2012; 67: 924-30.

Suzuki Y.

IMPROVEMENT OF PSORIASIS AND CHRONIC ERUPTION AFTER TAKING SGLT2 INHIBITOR: IPRAGLIFLOZIN IN DIABETES OF JAPANESE

Diabetes Research and Clinical Practice, Vol.106, S266

Published in issue: November, 2014

Change of Grip Strength and Back Strength after SGLT2 inhibitors treatment in diabetes
SGLT2 inhibitors often improve muscle strength.

Background:
SGLT2 inhibitor (SGLT2i) has an effect to reduce lean tissue mass as well as fat mass (1). Weakness and / or sarcopenia are the concerns when SGLT2i is prescribed onto the thin patients. Therefore, we examined the change of grip strength (GS) ) and back strength (BS) before and after the SGLT2i treatment.

Method:
112 diabetes patients of Japanese were subjected.
Male 91, Female 21.
They were all treated with ipragliflozin, luseogliflozin, dapagliflozin, or tofogliflozin for over at least 4 weeks and more.
GS and BS were measured before and after the months of SGLT2i treatment.

Result:
In male, 30% showed increase of GS and BS. 41% showed increase of GS and decrease of BS. Depending, 71% showed increase of GS. 5% showed decrease of GS and increase of BS. 24% showed decrease of both GS. and BS. Depending, 65% showed decrease of BS.
In female, 62% showed increase of GS and BS. 14% showed increase of GS and decrease of BS. Depending, 76% showed increase of GS. 14% showed decrease of GS and increase of BS. 10% showed decrease of both GS. and BS. Depending, 24% showed decrease of BS.
In total, both male and female patients are likely to increase GS. About 71-76% patients showed increase of GS, indicating no sexual difference. In contrast, more percentage of patients showed decrease of BS in male than in female. It seems that male patients are likely to lose BS, while female patients are resistant to lose BS.

Conclusion: Conclusion:
In general, BS is a parameter of total muscle power in healthy Japanese. Therefore, the muscle power loss is reflected by the decease of BS. This study confirmed that the loss of muscle power could occur in diabetes patients under SGLT2i treatment. However, although SGLT2i reduces lean tissue mass and BS, it increased GS in majority of diabetes patients. It seems as if increase of GS compensates decrease of BS, making the muscle power balance homeostatic. In diabetes, GS is decreased under hyperglycemia with diabetes (2). Therefore, improvement of hyperglycemia itself could make the GS stronger. Second, nerve conduction velocity recovers rapidly after the improvement of hyperglycemia. Because GS depends on nerve conduction function, the improvement of velocity by SGLT2i therapy might make the grip power stronger. Third, BS is dependent on musculi trunci and GS is dependent on musculi thoracici SGLT2i ameliorate hypertriglycemia and insulin resistance, which causes a reduction of TGA in muscle. Because muscli trunci is richer of TGA than musculi thoracici, the expression of SGLT2i's effect could appear stronger in muscli trunci than in muscli thoracici, which makes the different patterns of muscle power and their change between GS and BS.
In conclusion, this is a preliminary study. But the phenomena are intriguing to understand the potential mechanism of SGLT2i therapy. Therefore, further profound study is needed in practice.

References: References:
1: Bolinder J et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2013 Aug 1.doi: 10.1111 / dom.12189. [ Epub ahead of print],
2: Cetinus E. et al. Hand grip strength in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract. 70: 278-86.2005
3: Man ZW et al. Decrease in triglyceride accumulation in tissues by restricted diet and improvement of diabetes in Otsuka Long-Evans Tokushima fatty rats, a non-insulin-dependent diabetes model. Metabolism 49: 108-14.2000

Suzuki Y.

CHANGE OF GRIP STRENGTH AND BACK STRENGTH AFTER SGLT2 INHIBITORS TREATMENT IN DIABETES

Diabetes Research and Clinical Practice, Vol.106, S265-266

Published in issue: November, 2014

A Study on Skin Disorders of SGLT2 Inhibitors in Japan

Consideration of skin complication caused by treatment of SGLT2 inhibitor in Japanese

HDC Atlas Clinic Yoshihiko Suzuki

Many skin disorders were reported in the spring of 2014 for SGLT2 inhibitors (hereinafter abbreviated as SGLT2i). I reported skin disorders in 17 of 142 cases (12%) with ipragliflozin (hereinafter abbreviated as ipra) 1). Drug eruption usually occurs about 4 days to several weeks after oral administration, and the symptoms are diverse. However, SGLT2i-related drug eruption in the spring of 2014 has various symptoms, and each SGLT2i has a cross-reactivity 2), and it is said that it is "unusual" that it occurs in a short period of time after the start of oral administration.
The reason why SGLT2i skin disorders became a turmoil only in Japan is inferred below. 1: In the interview form, the frequency of skin disorders exceeded 2%, and it was released by ipra, which is more likely to cause skin disorders than other SGLT2i 3). 2: The drug eruption that occurs from the first tablet on the first day of oral administration may have a latent allergic predisposition due to another cause. It may have just become apparent as a type I skin allergy triggered by oral administration of SGLT2i. 3: Throughout the year, the incidence of skin disorders decreased from summer to autumn and winter in new prescription cases of SGLT2i. According to the results of side effects of ipra's information provision activities (reported in February 2015), drug eruption was as low as 0.3%, probably because it was prescribed in a time or area where PM2.5 did not affect. At our hospital, we prescribed it in the spring of 2014 when cypress and PM2.5 were scattered, which may be the cause of frequent skin disorders.
From the above, the background of SGLT2i skin disorders is the accident that ipra, which has a high probability of developing skin disorders, was first released, and the accident that another SGLT2i was released immediately afterwards and had a cross-reactivity, and the effect was small at the time of SGLT2i trial. However, PM2.5, which had a widespread effect after marketing, was latent before taking SGLT2i, and it coincided with the time when hinoki was scattered, making it easy to cause skin allergies. Isn't it? "
In addition, for example, it is possible that there was a high awareness of reporting side effects at the time of launch, but if so, there should be similar uproar in Western countries. It is more scientific to think that some kind of interference factor was accidentally added between before and after the market, causing a turmoil.
PM2.5 has become a problem and there have been recent reports on the correlation with type I skin allergies4,5). It is common sense to assume PM2.5 as the cause of health damage that concentrates from spring to early summer after 2013, and this consideration is logically easy to think about 6,7). Furthermore, this year, again, within a week after PM2.5 was scattered, the number of skin disorders in patients taking SGLT2 inhibitors increased, and reproducibility was confirmed. ..

Citations

1. Suzuki Y. Skin complication of SGLT2 inhibitor treatment in Japanese. Diab.Res.Clic. Prac. 106, sup1: 272, 2014

2. Japan Diabetes Society: Recommendation from "Committee on the proper use of SGLT2 inhibitors" (in Japanese) http://www.jds.or.jp/modules/important/index.php?page=article&storyid=48

3. Interview Form of ipragliflozin. Http://www.info.pmda.go.jp/go/interview/1/800126_3969018F1022_1_1F

2014. p73 (in Japanese)

1. Otani S , Onishi K , Mu H , Hosoda T , Kurozawa Y Ikeguchi M. Associations between subjective symptoms and serum immunoglobulin E levels during Asian dust events. Int J Environ Res Public Health. 11: 7366-41, 2014

2. Takeshita S, Tokunaga T, Tanabe Y, Arinami T, Ichinose T, Noguchi E.

Asian sand dust aggregate causes atopic dermatitis-like symptoms in Nc / Nga mice. Allergy Asthma Clin Immunol. 11: 3,2015

1. Otani S, Onishi K, Mu H, Yokoyama Y, Hosoda T, Okamoto M, Kurozawa Y. The relationship between skin symptoms and allergic reactions to Asian dust. Int J Environ Res Public Health. 9: 4606-14, 2012

2. Ogi K, Takabayashi T, Sakashita M, Susuki D, Yamada T, Manabe Y, Fujieda S. Effect of Asian sand dust on Japanese cedar pollinosis. Auris Nasus Larynx. 41: 518-22, 2014