Evaluation of the use of Sitagliptin in adult patients with type 2 Diabetes mellitus

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1 RESEARCH JOURNAL OF MEDICINE AND MEDICAL SCIENCES (1): 9-15 ISSN: X Journal home page: RESARCH ARTICLE Evaluation of the use of Sitagliptin in adult patients with type 2 Diabetes mellitus 1 Nabil Alama, 2,3 Ahmed A. Elberry, 2 Huda N. Alama, 2 Rashida A. Rashid, 2 Reem A. Faris, 2 Ameen M. Almohammadi 1 Department of Cardiology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia 2 Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia 3 Department of Clinical Pharmacology, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt ABSTRACT Background: Sitagliptin (SITA) prescription in treatment of diabetes mellitus is growing and becoming more prevalent in recent years since introduction in Saudi Arabia in Objectives: The aim of the current study is to evaluate the efficacy and Safety of SITA in the treatment of patient with type 2 diabetes. Patients and methods: retrospective chart review of 24 adult patients with type 2 Diabetes mellitus aged 42 to 77 years who were treated with Sitagliptin (Januvia ) for at least 1 year. Data was collected on Diabetes type, other antidiabetic drugs used concomitantly with Sitagliptin, co-morbidities, Body mass index, HBC1A% before and after 6 months on Sitagliptin. Results: Of the 24 patient reviewed, 16 (66.5%) were men and 8 (33.5%) were women. The average age was 42 to 77 years (mean = 59 years). The duration of treatment ranged from 6 months to 1.5 years. Of the 24 patients, 4 (16.6%) had become controlled (their Hbc1a has become <7%), Hbc1a% was reduced in 6 (25%) patients by more than 1.5%, and 14 (58.4%) patients still wasn t controlled. Conclusion: Our results confirm that Sitagliptin, a DPP-4 inhibitor is an effective adjunctive therapy in the treatment of type 2 diabetes mellitus in Saudi population, with possible no evident side effect. Key words: Diabetes mellitus, Dipeptidyl-peptidase, Incretin, Sitagliptin, Saudi Arabia, Type 2 diabetes. Address for Correspondence: Ahmed A. Elberry, Department of Clinical Pharmacy, Faculty of Pharmacy, King Abdul-Aziz University Jeddah 21589, Saudi Arabia Phone: Fax: berry_ahmed@yahoo.com Received 3 January 2016; accepted 26 April 2016; published 4 May 2016 INTRODUCTION Diabetes Mellitus (DM) is a global widespread health problem, Recent WHO statistics provide that worldwide, about 422 million people have diabetes, and showed that 1.8 million deaths are directly attributed to diabetes each year (WHO, 2016). Furthermore, in Saudi Arabia, DM is a prevalent health problem. Previous studies indicates that almost one in five Saudis of age 30 years or older had DM (El-Hazmi et al, 1996). In addition, Alqurashi et al (2011) found that nearly 30% of Saudi adults have DM. Diabetes mellitus is a group of metabolic diseases chiefly characterized by chronic hyperglycemia resulting from insufficient insulin action and approximately 90% of diabetic patients have type 2 diabetes mellitus (American Diabetes Association 2014). Type 2 diabetes Characterized by impaired insulin secretion, and or resistance to insulin action, and associated with both microvascular and macrovascular complications (Meigs 2003). A 1% decrease in HbA1c levels prevents the onset of microangiopathy by 37% according to the United Kingdom Prospective Diabetes Study (Stratton et al., 2000) Dipeptidyl-peptidase 4 (DPP-4) is a cell-surface protease that plays a role in glucose homeostasis through proteolytic inactivation of the incretin (Lambier et al., 2003). In type 2 diabetic patients, the Overall incretin effect is diminished (Nauck et al., 1993), however, it can be enhanced by inhibiting the incretin-disabling Open Access Journal Published BY AL RAZI Network for Medical sciences and Molecular Biology Publication 2016 ARNMSMB Publisher All rights reserved This work is licensed under the Creative Commons Attribution International License (CC BY). To Cite This Article: Nabil Alama, Ahmed A. Elberry, Huda N. Alama, Rashida A. Rashid, A. Faris, Ameen M. Almohamadi., Evaluation of the use of Sitagliptin in adult patients with type 2 Diabetes mellitus. Research Journal of Medicine and Medical Sciences, 11(1): 9-15, 2016

2 10 Nabil Alama et al, 2016/ Research Journal of Medicine and Medical Sciences, 11(1) January 2016, Pages: 9-15 enzyme DPP-4 (Kim and Lee 2010). DPP-4 inhibitors probably exert most, if not all, of their pharmacological effects in humans by inhibiting the degradation of GLP-1. Through this function, they cause some of the same effects of GLP-1, including stimulation of insulin secretion, inhibition of glucagon secretion, and enhancement of β-cell mass (White 2008). The first DPP-4 inhibitor approved in the United States was sitagliptin in October Oral sitagliptin tablets are administered either as monotherapy or in combination with other oral antidiabetic agents (Drucker et al., 2010). Sitagliptin is generally well tolerated and weight-neutral, with a low risk of hypoglycemia except when combined with sulfonylureas or insulin (Dhillon, 2010). In Saudi Arabia, sitagliptin was approved in 2008 and recently, sitagliptin prescription is growing and becoming more prevalent (Saudi Food and Drug Authority 2016). However, to our Knowledge, more data and research are required as the findings from Saudi subjects are limited. So, the aim of the present study is to investigate and evaluate the efficacy and possible side effects of Sitagliptin among Saudi population Patients And Methods: A retrospective chart review was performed at Suliman Fakeh Hospital (SFH), Jeddah, Saudi Arabia, on adults with type2 Diabetes Mellitus who were treated with Sitagliptin (Januvia) from 2014 to The study was done after approval from SFH review board and it was conducted to assess the efficacy and safety of Sitagliptin as adjunctive therapy in type 2 diabetic adult patients. Patients who are treated with Sitagliptin were identified retrospectively, and data was collected on age, gender, diabetes type, other antidiabetic drugs use concomitantly with Sitagliptin, co-morbidity with the diabetes patients, body mass index, and HBC1A% before and after 6 months on Sitagliptin. The FDA approved indications for Sitagliptin were used in patient selection: only patients with type2 diabetes mellitus, in adult patient who were treated with sitagliptin for at least 1 year. The initial study group of 40 was reduced to 24 as a result of insufficient data available in 16 patients. Data are analyzed descriptively while before and after Sitagliptin use. Results: Table (1) shoes the baseline characteristics of the patients, while all the patient data are shown in table (2). Of the 24 patient reviewed, 16 (66.5%) were men and 8 (33.5%) were women. The average age was 42 to 77 years (mean = 59years). 2 patients were smokers. 8 patients have received insulin. With the exception of 2 patients who were just receiving insulin, all the patients has received concomitant antidiabetic medication.the most common antidiabetic drugs included, glimepiride, gliclaide, liraglutide (Figure 1). Hypertension were the predominant Co-morbidity 20(83.3%). Other co-morbidity included Dislipidemia 13(54.2%), Coronary artery disease 6(25%), fatty liver 2 (8.3%), Renal Impairment 1(4.2%), Hypothyroidism 1 (4.2%), and others 4 (16.7%) including Chronic Obstructive Pulmonary Disease, Anemia, Osteoporosis, Prostate hyperplasia (1 patient each) (Figure 2). The duration of treatment ranged from 6 months to 1.5 years. Of the 24 patients, 4 (16.7%) had become Controlled (their Hbc1a has become <7%), Hbc1a% was reduced in 6 (25%) patients by more than 1.5%, and 14 (58.3%) patients still wasn t controlled (Figure 3). In addition, the present study showed that Hbc1a was 8.93±1.8 before Stita use while it was 8.19±1.5 after using Sita and this difference was siginificant (figure 4). Table 1: Baseline characteristics of the patients n 24 patients Age (mean) 59 Male % 66.5% Mean duration of DM 12.1 year HbA1c% before Sitagliptin (mean) 8.9 Smoking number (%) 2 (0.8) BMI (Mean) 34.8 Sitagliptin duration (Mean) 1.2 year

3 11 Nabil Alama et al, 2016/ Research Journal of Medicine and Medical Sciences, 11(1) January 2016, Pages: 9-15 Table 2: Patients data for those who received Sitagliptin as adjuvant therapy (: hypertension, : dyslipidemia, COPD: chronic obstructive pulmonary disease, : coronary artery disease, BPH: benign prostatic hyperplasia) ID Age(Yr)/ Concomitant Duration use of Hba1c before Hba1c After BMI Gender medications Sitagliptin 6 months 6 months Co-morbidity /M yr 2 56/M yr /M yr /M /M /M /F /F /F /F /M 28.6 Liraglutide Liraglutide 6 months 1.5 yr yr 1.4 yr 1.2 yr 8 months 12 42/M yr 13 59/M yr 14 52/M yr 15 71/M /F /M /M /M /F /M /F /F /M yr 1.4 yr Anemia COPD HLD Osteoporosis Hypothyroidism Fatty liver Osteoporosis BPH HLD Renal impairment Fatty liver None IHD

4 12 Nabil Alama et al, 2016/ Research Journal of Medicine and Medical Sciences, 11(1) January 2016, Pages: 9-15 Fig. 1: Concurrent drugs with Sitagliptin Fig. 2: Co-morbidities with the diabetes patients Fig. 3: Patients Hbc1a% reduced by >1.5% and Patients Hbc1a less than 7% (controled)

5 13 Nabil Alama et al, 2016/ Research Journal of Medicine and Medical Sciences, 11(1) January 2016, Pages: 9-15 Fig. 4: The patient hbc1a% before 6 months and after 6 months of sitagliptin Discussion: Despite much progress, diabetes remains the leading cause of blindness, kidney failure and non-traumatic lower limb amputations due to microvascular and macrovascular complications (Bailey 2011). Several studies have shown that strict glycemic control is a most important factor in the prevention of these complications (Strattin et al., 2000). The goal for T2DM treatment is to administer sufficient amounts of insulin in vivo to effectively control plasma glucose without causing severe hypoglycemia. Therefore drugs with different mechanisms of action are needed. Sitagliptin is a DPP-4 inhibitor antidiabetic drug, approved in Saudi Arabia since The DPP 4 inhibitors stimulate insulin secretion and suppress glucagon secretion by inhibiting the degradation of active incretin, which is secreted depending on blood glucose levels (Thornberry et al., 2009). Its pharmacokinetic advantage include good absorption (approximately 80% excreted unchanged in the urine) with an apparent terminal half-life ranging from 8 to 14 hours. Renal clearance of sitagliptin was largely uninfluenced by the dose administered (Hermin 2005). It has been demonstrating effectiveness as adjunctive therapy for type 2 diabetes mellitus. The current study showed that HbA1c percentage was been reduced in 41.6% of the patients. Moreover, 16.6% of the patients had become well controlled and achieved the HbA1c goal which is less than 7%. On the other hand, most previous studies of type 2 diabetic patients treated with Sitagliptin demonstrated reduction in HbA1c percentage ranging from 0.82% to 1.4% (Bailey 2011). Kim et al., 2011 found that more than 81% of patients were found to have improved glucose tolerance and that sitagliptin treatment exerts significant effects in patients who have decreasing secretory capacity in pancreatic beta cells. Williams and Johnson (2010) studied the effect of Sitagliptin which demonstrated additive efficacy when combined with metformin in a study of 1,091 patients with type 2 diabetes. In addition, Williams-Herman et al. (2010) revealed that combining sitagliptin with metformin is more effective than increasing the metformin dose. More recently, Kondo et al., 2016 found that Sitagliptin monotherapy has better effect on insulinogenic index than glimepiride monotherapy in Japanese patients with type 2 diabetes mellitus. Moreove, Vilsbol.T and Rosenstock.J (2010) found evidence supporting the efficacy of Sitagliptin as an adjunct to insulin in patients with long-standing type 2 diabetes. Adding Sitagliptin to ongoing insulin treatment in 641 patients with type 2 diabetes significantly reduced Hba1c compared with placebo over 24 weeks (Vilsboll et al., 2010). No hypoglycemia or other adverse events associated with Sitagliptin were documented in this study. secretion stimulated by sulfonylureas is independent of the glucose concentration, while DPP-4 inhibitors increase an active form of incretin peptide by DPP-4 inhibition and potentiate glucose-dependent insulin secretion. Accordingly, DPP-4 inhibitors are associated with lower frequency of hypoglycemia and are weight neutral (Zhang et al., 2014, Esposito et al., 2014). On the other hand, the observed adverse event profile of Sitagliptin among type 2 diabetic patients in previous studies was mainly seen more with the combination with. Diarrhea and nausea occurred significantly more often in patients taking than in patients taking Sitagliptin (Aschner et al., 2010) Conclusion: In conclusion, the present study showed that Sitagliptin, one of the DPP-4 inhibitors, is an effective adjunctive therapy in the treatment of type 2 diabetes mellitus in Saudi population, with possible no evident side effect. Further controlled studies may be required in different populations, in larger groups and for longer

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