Impact of sitagliptin combination therapy and hypoglycemia in Japanese patients with type 2 diabetes: a multi-center retrospective observational cohort study

Abstract

Background Patients with diabetes are at higher risk of developing polypharmacy because of the high frequency of comorbidities. There have been several reports on the hypoglycemic risk of the combination of hypoglycemic agents and other medications. This study aimed to investigate the hypoglycemic risk of drug-drug interaction between sitagliptin and other oral hypoglycemic agents or antihypertensive agents in Japanese patients with type 2 diabetes. Methods From January 2010 to March 2012, a total of 3247 patients were recruited and evaluated at outpatient clinics at Juntendo University Hospital, other satellite hospitals, and private clinics. This study was a sub-analysis of the Sitagliptin Registration Type 2 Diabetes-Juntendo Collaborating Project. Participants were limited to those treated with oral hypoglycemic agents, excluding insulin users, to investigate the association of the first hypoglycemic events with oral hypoglycemic agents or other medications within 6 months after starting sitagliptin. The factors related to the first hypoglycemic event were analyzed using Cox regression analysis. Results In total, 2956 patients with a mean age of 65.1 ± 11.3 years were included. A total of 46 hypoglycemic events (1.6%) were observed. One patient had severe hypoglycemia followed by emergency transport to the hospital. Sitagliptin was not associated with hypoglycemia, but its combination with sulfonylurea (hazard ratio: 4.42, 95% confidential interval: 1.36–14.42) or β-blocker (hazard ratio, 3.50, 95% confidential interval: 1.54–7.96) was significantly associated with hypoglycemia. Conclusions The drug-drug interactions between sitagliptin and sulfonylurea or β-blocker likely increases the hypoglycemic risk in Japanese patients with type 2 diabetes. Pharmacists should consider potential adverse events from drug-drug interaction in type 2 diabetes with polypharmacy, particularly those who are managed by several doctors or clinics.

Fasting biochemical hypoglycemia and related-factors in non-diabetic population: Kanagawa Investigation of Total Check-up Data from National Database-8

“…Hypoglycemia frequently occurs in diabetic patients undergoing pharmacotherapy and is difficult to predict[ 1 - 4 ]. In the present study, we have demonstrated that FBH also occurs in non-diabetic people, although the prevalence was very low (less than 1.0% of the total) in the general population studied, in contrast to that in diabetic patients[ 12 , 13 ]. This prevalence of FBH is not dissimilar to that of hypoglycemia (0.2%-0.5%) in non-diabetic people[ 3 , 5 ].…”

Impact of sodium‐glucose cotransporter‐2 inhibitors on the risk of hip fracture in older patients in Japan using a nationwide administrative claims database: A matched case–control study

“…However, in the risk assessment of SGLT2 inhibitor administration prior to hip fracture, patients within 30 days of treatment initiation showed a tendency for increased risk of hip fracture. Possible factors that may increase the risk of hip fractures include falls due to hypoglycemia at the initiation of antidiabetic agents 24,25 and increased urine volume caused by SGLT2 inhibitors, 26 as well as changes in bone density associated with weight fluctuations. However, there was no significant impact observed that would increase the risk to a statistically significant level.…”

Diyabet Merkezden Takipli Tip 2 Diabetes Mellitus Hastalarında Hipoglisemi Sıklığı ve Hipoglisemi Korkusu

“…Yapılan çalışmalarda tip 2 DM hastalarındaki hipoglisemi sıklığı %1,6-%57,44 arasında değişkenlik göstermektedir. 1,7 Birinci basamak sağlık hizmetleri ile hastane temelli sağlık hizmetlerinin kıyaslandığı çalışmalarda ise, DM hastalarında hipoglisemi sıklığı birinci basamak sağlık hizmetlerinde %13,5-25,1 iken, hastane temelli sağlık hizmetlerinde %32,1-74,9 olarak tespit edilmektedir. 8,9 Ayrıca, yapılan çalışmalarda bizim çalışmamızla benzer şekilde, DM hastalarının hipoglisemi sıklığı birinci basamak sağlık hizmetlerinde hastane temelli sağlık hizmetlerine göre düşük saptanmıştır.…”

“…10 Yapılan bazı çalışmalarda hipoglisemi olan hastalarda DM süresi açısından fark gözlenmezken, bazı çalışmalarda DM süresi ile hipoglisemi varlığı arasında ilişki tespit edilmiştir. 7,[11][12][13][14][15][16] Yapılan çalışmalarda hem ciddi hem de hafif hipoglisemi atağı sıklığı insülin kullananlarda yüksek gözlenmiştir. 12,16,17 Bir çalışmada tip 2 DM hastalarında sadece insülin kullanımının hipoglisemi riskini 6,5 kat arttırdığı bulunmuştur.…”

“…Tip 1 ve tip 2 DM hastalarında yapılan bir çalışmada da benzer şekilde, hipoglisemi atağını yönetebilme sıklığı birinci basamak sağlık hizmetlerinde hastane temelli sağlık hizmetlerine göre yüksek saptanmıştır. 7 Çalışmamızın kısıtlılığı, hipoglisemi tanısının sadece sabah açlık kan glukoz düzeyi ile konması ve gün içerisinde veya nokturnal hipoglisemi ataklarının değerlendirilmemesidir. Çalışmamızın güçlü yanı ise, ülkemizde DM'in en sık komplikasyonu olan hipoglisemi açısından aile hekimliği yönelimli yaklaşım ile hastane yönelimli yaklaşımın değerlendirildiği çalışma sayısı azdır.…”