Oral Antihyperglycemic Agents Research Articles

Real World Study of Effectiveness of Gemigliptin Add-On Therapy in Type 2 Diabetes Mellitus

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agents that increase endogenous levels of incretin hormones and lead to an increased insulin level and a reduced glucagon level in a glucose-dependent way. Gemigliptin, is a potent, selective, competitive, and long-acting DPP-4 inhibitor. The objective of our study was to evaluate the realworld efficacy and safety of gemigliptin. Materials and methods: A real-world prospective, observational, single-center study conducted in the Endocrinology Department, of a tertiary care hospital. 60 patients were included with 22 (36.7%) female patients. The treatment options consisted of uncontrolled metformin monotherapy, dual combination therapy, triple oral anti-hyperglycemic agents, metformin, and basal insulin combination. Weight, body mass index (BMI), fasting plasma glucose (FPG), 2 hours post postprandial glucose (PPG), HbA1c% were documented at baseline and followed up at 3 months. Results: The baseline HbA1c, FPG and PPG were 9.50 ± 2.24 %, 176.71 ± 67.076 mg/dL, 243.37 ± 93.97 mg/dl respectively. After 3 months of additional gemigliptin therapy, HbA1c, FPG, and PPG were significantly reduced to 8.24 ± 1.83%, 144.32 ± 50.664, 184.93 ± 69.66 respectively. Conclusions: In real world settings, gemigliptin, a new DPP-4 inhibitor was found to be effective, safe and well tolerated as add-on therapy in adult type 2 diabetes mellitus (T2DM) subjects.

Insulin use in Type 2 diabetic patients: a predictive of mortality in covid‑19 infection

IntroductionStarting December 2019, the world has been devastated by the rapid spread of coronavirus disease 2019 (Covid-19). Many risk factors have been associated with worse outcomes and death from Covid-19 pneumonia including having diabetes mellitus. To date, it is not clear if all group of diabetics share the same risk of complications with COVID-19 infection. This study aims to compare disease severity and mortality rate in insulin users versus non-insulin users.MethodsIn this retrospective case–control study conducted at the largest health care network in New York state, we included adult, diabetic patients admitted from March 2020 to October 2020 with Covid-19 pneumonia. We compared the baseline characteristics in addition to outcomes of diabetic patients on home insulin (cases) and non-insulin user diabetics (controls). In addition, to determine if home insulin use is associated with an increased mortality, we conducted a cox regression analysis.ResultsWe included 696 patients in the study period with a median age of 57 years, interquartile range [IQR] 51–62, and median body mass index 29.9 (IQR: 26–34.7). The majority (476 [68%]) were males. We identified 227 cases (33%) and 469 controls (67%). More cases than controls were hypertensive (74% vs 67%, p = 0.03), on ACE/ARB (50% vs 42%, p = 0.05), and had a hemoglobin A1c > 8.1 (71% vs 44%, p < 0.001). More cases had AKI (52% vs 38%, p < 0.001), however no significant differences were found in intubation rates (26% vs 24%, p = 0.54), detection of pulmonary embolism (4% vs 6%, p = 0.19) or death rate (15% vs 11%, p = 0.22) comparing cases and controls. In a multivariate analysis, we found that home insulin use was independently associated with increased risk of death: Hazard ratio: 1.92, 95% confidence interval (1.13–3.23).ConclusionWe showed herein that diabetic patients on home insulin with COVID-19 pneumonia, have worse outcomes and increased mortality compared to diabetics on oral antihyperglycemic agents. Close monitoring of insulin-dependent type II diabetic patients is needed in the current pandemic.

680-P: Effect of the FreeStyle Libre System on Diabetes Treatment for People with T2D: Results from a Retrospective Cohort Study Using Canadian Private Payer Claims Database

Introduction: Therapeutic inertia is a major contributor to people with diabetes not achieving glycemic goals. We assessed for patients with T2D the impact of using the FreeStyle Libre system (FSL) vs. blood glucose monitoring (BGM) on treatment intensification. Method: We carried out a matched retrospective cohort study using secondary private payer claims data including &amp;gt;30 million diabetes drug and device claims filled by over 850,000 patients with T2D &amp;gt;18 in Canada over 24 months. Each month, patients were classified by level of therapy progression: 1. No diabetes drug therapy; 2. Mono Oral Antihyperglycemic Agents (OHAs) ; 3. Dual OHAs; 4. Triple OHAs; 5. Quad or more OHAs; 6. Injectable GLP1-RA (±concomitant OHAs) ; 7. Basal insulin (±concomitant OHAs) ; 8. MDI insulin (±concomitant OHAs) . Results: A total of 373,871 patients met the inclusion criteria. Across all treatment cohorts, the FSL treatment groups were found to have a statistically higher probability of treatment intensification relative to BGM: Conclusion: Reimbursement of FSL for patients with T2D in Canada is associated with decreased time lag for glucose lowering therapy compared to those using BGM alone. These findings suggest that FSL data impact clinicians to facilitate earlier and more intensive therapy modifications and thus reduce treatment inertia. Disclosure S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation. F.Levrat-guillen: Employee; Abbott. Funding Funded by Abbott Diabetes Care

Safety and Efficacy of Inpatient Diabetes Management with Non-insulin Agents: an Overview of International Practices.

Purpose of ReviewThe field of inpatient diabetes has advanced significantly over the last 20 years, leading to the development of personalized treatment approaches. However, outdated guidelines still recommend the use of basal-bolus insulin therapy as the preferred treatment approach, and against the use of non-insulin anti-hyperglycemic agents.Recent FindingsSeveral observational and prospective randomized controlled studies have demonstrated that oral anti-hyperglycemic agents are widely used in the hospital, including studies of DPP-4 agents and GLP-1 agonists.SummaryWith advances in the field of inpatient diabetes management, a paradigm shift has occurred, from an approach of recommending “basal-bolus regimens” for all patients to a more precision medicine option for hospitalized non-critically ill patients with type 2 diabetes.

Disposition study of the novel dipeptidyl peptidase 4 inhibitor cetagliptin in rats

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a class of oral antihyperglycemic agents and therapeutic approach for type 2 diabetes. Cetagliptin is a novel oral and selective DPP-4 inhibitor and developed as a promising candidate for treatment of type 2 diabetes mellitus. This study aimed to evaluate the metabolism and excretion of cetagliptin in Sprague-Dawley (SD) rats, and to detect and identify metabolites of cetagliptin. The SD rats were administered with a single oral dose of 6 mg/kg with approximately 100 µCi of [14C] cetagliptin. The mean total recovery of radioactivity was 90.20% within 168h in SD rats excreta. Cetagliptin was the major radioactive component in SD rats plasma, urine and eliminated primarily by faecal excretion. The recovery of cetagliptin in urine and feces was 25.15% and 13.85% of the dose, respectively. Cetagliptin was well absorbed after oral administration in SD rats based on the total recovery of radioactivity in BDC SD rats bile and urine. Six major metabolites were observed and identified in SD rats, comprising 0.20 to 4.53% of total plasma AUC. These major metabolites were the hydroxylated, N-sulphate and N-carbamoyl glucuronic acid conjugates of the cetagliptin, two metabolites formed by glucuronide of a hydroxylated metabolite.

Short-Term Metformin Treatment Enriches Bacteroides dorei in an Obese Liver Steatosis Zucker Rat Model.

Obesity is the leading cause of health-related diseases in the United States and World. Previously, we reported that obesity can change gut microbiota using the Zucker rat model. Metformin is an oral anti-hyperglycemic agent approved by the FDA to treat type 2 diabetes (T2D) in adults and children older than 10 years of age. The correlation of short-term metformin treatment and specific alterations to the gut microbiota in obese models is less known. Short-term metformin has been shown to reduce liver steatosis. Here we investigate the effects of short-term metformin treatment on population of gut microbiota profile in an obese rat model. Five week old obese (n = 12) female Zucker rats after 1 week of acclimation, received AIN-93 G diet for 8 weeks and then rats were randomly assigned into two groups (6 rats/group): (1) obese without metformin (ObC), or (2) obese with metformin (ObMet). Metformin was mixed with AIN-93G diet at 1,000 mg/kg of diet. Rats were weighed twice per week. All rats were sacrificed at the end of metformin treatment at 10 weeks and fecal samples were collected and kept at −80°C. Total microbial DNA was collected directly from the fecal samples used for shotgun-metagenomics sequencing and subsequently analyzed using MetaPlAn and HUMAnN. After stringent data filtering and quality control we found significant differences (p = 0.0007) in beta diversity (Aitchison distances) between the ObC vs. ObMet groups. Supervised and unsupervised analysis of the log-ratios Bacteroides dorei and B. massiliensis vs. all other Bacteroides spp., revealed that B. dorei and B. massiliensis were enriched in the ObMet group, while the remaining Bacteroides spp. where enriched in the ObC group (p = 0.002). The contributional diversity of pathways is also significantly associated by treatment group (p = 0.008). In summary, in the obese Zucker rat model, short-term metformin treatment changes the gut microbiota profile, particularly altering the composition Bacteroides spp. between ObC and ObMet.

Antenatal insulin therapy in gestational diabetes mellitus: validation of the new Brugmann scores

Background Following the adoption of the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for gestational diabetes mellitus (GDM) diagnosis by the World Health Organization (WHO) in 2014, many investigators have tried to identify independent risk factors for antenatal insulin therapy (AIT). The purpose of the current study is to build and validate a score that stratifies patients according to their need for AIT. Methods All pregnant women diagnosed with GDM according to the IADPSG definition were included. Group 1 comprised patients of 2018, and group 2 comprised patients of 2019. Each group was divided into two subgroups: subgroup A comprised patients diagnosed according to the 75-g oral glucose tolerance test (OGTT), and subgroup B comprised patients diagnosed according to fasting plasma glucose (FPG). Results A total of 1298 patients were included; 19.3% of those diagnosed by OGTT and 40.9% by FPG required AIT. The risk for AIT was stratified as low, moderate, and high. Brugmann FPG score comprised six risk factors and Brugmann OGTT score 12. Higher scores were associated with higher risk for AIT. The use of these scores in the two subgroups of group 2 showed no statistical differences compared to group 1. Conclusions Both Brugmann FPG and OGTT scores may be useful to stratify patients with GDM according to their need for AIT. Future studies should be conducted to prospectively validate these scores, and to examine whether or not using oral anti-hyperglycemic agents in a high-risk group may decrease the need for AIT.

A Review on HPLC Method Development and Validation for Gliptin Class: New Oral Antidiabetic Agents

Gliptin is the class of antidiabetic medicine also called as dipeptidylpeptidase-4. DPP-4 (dipeptidyl peptidase-4) inhibitors (or "gliptins") represent a class of oral anti-hyperglycaemic agents that inhibit the enzyme DPP-4, thus augmenting the biological activity of the "incretin" hormones (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]) Sitagliptin, Saxagliptin, Alogliptin, Linagliptin, Vildagliptin are the Gliptin class inhibitor for the treatment of type 2 diabetes mellitus and they decrease the breakdown of the incretin hormones such as glucagon like peptide 1 (GLP-1). All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life DPP-4. This paper is an updated review, providing an analysis of both the similarities and differences between the various compounds known as gliptins, currently used in the clinic (sitagliptin, saxagliptin, alogliptin linagliptin and vildagliptin). This paper discusses the pharmacokinetic and pharmacodynamic characteristics of gliptins. In this review we complied analytical method development and determination of the Gliptin inhibitors. Table no.1, 2, 3, 4, 5, shows the analytical method development and validation of Sitagliptin, Saxagliptin, Alogliptin, Linagliptin, and Vildagliptin alone and with its combination by the HPCL method.

Real-World Evidence of Treatment with Teneligliptin/Canagliflozin Combination Tablets for Type 2 Diabetes Mellitus: A Post-Marketing Surveillance in Japan.

IntroductionTeneligliptin/canagliflozin combination tablets, which combine a dipeptidyl peptidase-4 (DPP-4) inhibitor (teneligliptin) and a sodium-glucose cotransporter 2 (SGLT2) inhibitor (canagliflozin), are a treatment option for type 2 diabetes mellitus (T2DM) in Japan. This post-marketing surveillance evaluated the real-world safety and effectiveness of teneligliptin/canagliflozin combination tablets, and changes in self-reported adherence to oral antihyperglycaemic agents.MethodsJapanese patients with T2DM who were prescribed the combination tablets for the first time between December 2017 and June 2018 were registered and followed up for 12 months. Safety and effectiveness were assessed in terms of adverse drug reactions (ADRs) and the changes in haemoglobin A1c (HbA1c) and body weight from baseline to 12 months with the last observation carried forward, respectively. Adherence was assessed using the Morisky Medication Adherence Scale 8.ResultsOverall, 821 patients were eligible for the analyses, including 733 who were prescribed the combination tablets for 12 months. ADRs and serious ADRs were reported in 4.38% and 0.85% of patients, respectively. Gastrointestinal disorders (0.97%) were the most common class of ADRs. No new safety concerns were identified beyond those described in the Japanese package insert. The changes in HbA1c and body weight from baseline to 12 months were − 0.43 ± 0.93% and − 1.29 ± 5.57 kg, respectively. The reductions in HbA1c at 12 months tended to be greater among patients who switched from either DPP-4 inhibitors (− 0.71 ± 0.89%) or SGLT2 inhibitors (− 0.51 ± 1.00%) relative to patients who switched from both (− 0.22 ± 0.88%). The decrease in body weight was greatest among patients who switched from DPP-4 inhibitors. An improvement in self-reported adherence to oral antihyperglycaemic agents occurred after switching to the combination tablets.ConclusionTeneligliptin/canagliflozin combination tablets were effective and associated with an improvement in adherence without new safety concerns in Japanese patients with T2DM in real-world clinical practice.Trial RegistrationJapicCTI-173778.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-02038-5.

Sodium\u2013glucose cotransporter 2 inhibitor-induced euglycemic diabetic ketoacidosis in a patient with coronavirus disease 2019: a case report

BackgroundSodium–glucose cotransporter 2 inhibitors are among the new-generation oral antihyperglycemic agents that have been used in the treatment of type 2 diabetes mellitus. With the recent coronavirus disease 2019 pandemic and rise of cases in the third wave, diagnosis of life-threatening euglycemic diabetic ketoacidosis may easily be overlooked or missed.Case presentationWe present the case of a 37-year-old Malay gentleman with underlying type 2 diabetes mellitus on empagliflozin, who presented to our hospital with symptomatic coronavirus disease 2019 infection and diabetic ketoacidosis. He developed severe rebound euglycemic diabetic ketoacidosis due to the continuous usage of empagliflozin for glycemic control alongside intravenous insulin.ConclusionsPhysicians should have a high index of suspicion in diagnosing and managing euglycemic diabetic ketoacidosis, including withholding treatment of sodium–glucose cotransporter 2 inhibitors during the acute management of diabetic ketoacidosis.

Prescribing patterns in type 2 diabetes mellitus outpatients at a tertiary care centre in Jaipur, India

Background: Over the last few years, an unexpected increase in the prevalence of diabetes in India have been witnessed. The present study was planned to analyse prescribing patterns of anti-hyperglycaemic drugs and assess the influence of Chief Minister's Free Drug Scheme in Rajasthan, India. It aimed to evaluate, monitor and if possible, suggest modifications in prescribing practices to make medical care rational and also to assist minimising adverse drug reactions (ADRs). Methods: This was a cross-sectional, observational study carried out for a 12-month period. A total 400 known patients of type 2 diabetes mellitus (T2DM) from endocrinology outdoor of SMS Medical College Hospital (a tertiary care hospital in Jaipur, Rajasthan, India) were recruited and their prescriptions were analysed using the World Health Organization (WHO) prescribing indicators. Results: Most commonly observed age group was of 40-50 years (mean age 53.76 ± 8.84), with a male preponderance (57.5 %). Among them, 67.5 % of patients were found to be obese (mean BMI 29.79 ± 3.26). All anti-hyperglycaemic were prescribed in their generic names only. Metformin was the most frequently prescribed anti-hyperglycaemic agent. Among the fixed dose combinations, the most common was that of glimepiride and metformin (40.75 %), while most prescribed add on anti-hyperglycaemic was teneligliptin (51.5 %), followed by pioglitazone (30.5 %). A total of 53.25 % of these patients received insulin along with oral anti-hyperglycaemic agents. Conclusion: The anti-hyperglycaemic agent prescribing among endocrinology outpatients at tertiary care hospital in Jaipur was found to be satisfactory.

Current State and Principles of Basal Insulin Therapy in Type 2 Diabetes.

Treatment with basal insulins is a fundamental part of management in many patients with type 2 diabetes mellitus. Multiple management schemes may be indicated in these individuals, for example, the use of oral antihyperglycemic agents with basal insulins (basal-supported oral therapy) or the combinations of basal insulins with glucagon-like peptide-1 receptor agonists; each of these strategies makes it easier to achieve glycemic control goals. A basic knowledge of the physiology, pharmacodynamic and pharmacokinetic aspects of the different basal insulins is essential to achieve treatment goals and compliance. This review addresses the principles of management with basal insulins.

Position of Sulfonylureas in the Current ERA: Review of National and International Guidelines.

Sulfonylureas (SUs) are one of the commonly prescribed oral anti-hyperglycemic agents (AHA) in low- and middle-income countries (LMICs), either in combination with metformin therapy or alone. However, concern about cardiovascular safety has limited the use of SUs in the management of type 2 diabetes mellitus (T2DM). Additionally, lack of uniformity in the national and international guidelines regarding the positioning of SUs in the management of diabetes has also been reported. The objective of this review was to assess the various national and international guidelines on diabetes management and understand the recommendations specific to SUs in various scenarios. A total of 33 national and international guidelines on the management of T2DM published in English were evaluated. These guidelines have considered the latest evidence and suggest the use of certain second-generation SUs as second-line therapy or in combination with other AHAs in select population and specific scenarios. Identification of the appropriate population, classification based on underlying risk, thorough assessment of the comorbid conditions, and a step-wise approach for the selection of appropriate SUs is essential for the effective management of T2DM. Additionally, cost-to–benefit ratio should be considered, particularly in LMICs, and SUs could continue to play an important role in such settings.

Empagliflozin Protects against Pulmonary Ischemia/Reperfusion Injury via an Extracellular Signal-Regulated Kinases 1 and 2-Dependent Mechanism.

Ischemia/reperfusion (I/R) injury of the lung can lead to extensive pulmonary damage. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are insulin-independent, oral antihyperglycemic agents used for treating type 2 diabetes mellitus (T2DM). Although their cardioprotective properties have been reported, their potential roles in pulmonary protection in vivo are poorly characterized. Here, we tested a hypothesis that empagliflozin, an SGLT2 inhibitor, can protect lungs in a mouse model of lung I/R injury induced by pulmonary hilum ligation in vivo. We assigned C57/BL6 mice to sham-operated, nonempagliflozin-treated control, or empagliflozin-treated groups. Pulmonary I/R injury was induced by 1-hour left hilum ligation followed by 2-hour reperfusion. Using quantitative polymerase chain reaction (q-PCR) and Western blot analysis, we demonstrate that SGLT2 is highly expressed in mouse kidney but is weakly expressed in mouse lung (n = 5-6 per group, P < 0.01 or P < 0.001). Empagliflozin improved respiratory function, attenuated I/R-induced lung edema, lessened structural damage, inhibited apoptosis, and reduced inflammatory cytokine production and protein concentration in bronchoalveolar lavage (BAL) fluid [P < 0.05 or P < 0.001 versus control group (CON)]. In addition, empagliflozin enhanced phosphorylation of pulmonary extracellular signal-regulated kinases 1 and 2 (ERK1/2) post-I/R injury in vivo (P < 0.001, versus CON, n = 5 per group). We further showed that pharmacological inhibition of ERK1/2 activity reversed these beneficial effects of empagliflozin. In conclusion, we showed that empagliflozin exerts strong lung protective effects against pulmonary I/R injury in vivo, at least in part via the ERK1/2-mediated signaling pathway. SIGNIFICANCE STATEMENT: Pulmonary ischemia-reperfusion (I/R) can exacerbate lung injury. Empagliflozin is a new antidiabetic agent for type 2 diabetes mellitus. This study shows that empagliflozin attenuates lung damage after pulmonary I/R injury in vivo. This protective phenomenon was mediated at least in part via the extracellular signal-regulated kinases 1 and 2-mediated signaling pathway. This opens a new avenue of research for sodium-glucose cotransporter-2 inhibitors in the treatment of reperfusion-induced acute pulmonary injury.

Safety of add-on sulfonylurea therapy in patients with type 2 diabetes using metformin: a population-based real-world study

IntroductionMetformin is the initial oral antihyperglycemic agent (OHA) of choice for most patients with type 2 diabetes (T2D). However, more than one agent is often required for optimal glucose control....

Mesangial sclerosis in a patient with type 1 diabetes following simultaneous pancreas-kidney transplantation despite maintenance of normoglycemia: a case report

BackgroundSimultaneous pancreas-kidney transplantation is considered a curative treatment for type 1 diabetes complicated by end-stage kidney disease. We report herein a case of mesangial sclerosis in a patient who underwent successful kidney-pancreas transplantation despite well-controlled glucose and excellent pancreatic allograft function.Case presentationA 76-year-old type 1 diabetic man who underwent a simultaneous pancreas-kidney transplantation 19 years prior presented with persistent nephrotic range proteinuria although creatinine was at his baseline (normal) level. Hemoglobin A1c and fasting glucose were well controlled without the use of insulin or oral antihyperglycemic agents. Serum lipase and amylase were within the reference range and there was no evidence of donor-specific antibodies. Kidney allograft biopsy was performed to evaluate proteinuria and showed diffuse capillary loop thickening and diffuse moderate to severe mesangial sclerosis resembling diabetic nephropathy.ConclusionsThis case demonstrates a case of mesangial sclerosis resembling diabetic nephropathy in a patient with good glucose control after simultaneous pancreas-kidney transplantation with excellent pancreatic allograft function.

Physicians’ Perspectives of Barriers to Insulin Initiation for Adults with Type 2 Diabetes Mellitus in Primary Health Care Centers (PHCCs), Tabouk Province - Kingdom of Saudi Arabia (KSA)

Aim: The goal of this study is to explore the family physicians’ perspectives of the barriers in initiating insulin for adult patients with Type 2 diabetes mellitus (T2DM) in their primary health care settings. Background: Insulin therapy often becomes necessary when oral anti-hyperglycemic agents are not enough, no longer effective or even as an initial choice. Timely insulin initiation was noticed to be a clinical problem among people with type 2 diabetes mellitus (T2DM) registered in primary health care centers (PHCCs) of Tabouk Province, KSA. Tackling this inertia or insulinophobia is a challenge in order to delay or prevent serious complications of uncontrolled diabetes. Our study and many other studies indicated that this therapeutic inertia is inappropriately due to many patient, system and physician-related factors. The present study aimed to investigate physicians’ perspectives of barriers to insulin initiation for adults with T2DM registered in PHCCs, Tabouk Province - KSA and to identify opportunities for better outcomes. Materials and Methods: This is a cross sectional study where 102 primary health care physicians (PHCPs) (58 females and 44 males) from multi PHCCs in Tabouk Health Province – Kingdom of Saudi Arabia (KSA), responded correctly to online reliable self-administered questionnaire (Cronbach alpha of 0.77344) to address their perspectives of barriers to insulin initiation for adult patients with T2DM. All participants were physicians attending PHCCs with well-equipped diabetes care clinics. Data were collected during a period from 6th – 17th June 2021. Participants included 11 (10.8%) family medicine consultants, 14 (13.7%) family medicine specialists and 77 (75.5%) general physicians. Results: 68.6 of the study participants had barriers in initiating insulin for their patients with T2DM. A significant statistical disproportional correlation was found between the level of specialty and the rate of reporting barriers to insulin initiation (P&lt;0.001). The top 10 listed barriers included the following: patients’ refusal to initiate insulin (71.4%), physicians’ fear of hypoglycemia (51.4%), inability of patients to perform home blood glucose monitoring (HMGM) (50%), physicians have no access to second opinion (44.3%), insufficient educational courses for physicians (37.1%), no family support for patients (34.3%), no clear MOH circular to support physicians’ initiation of insulin at PHCCs (28.6%) , insufficient hypoglycemic medications at PHCCs (25,7%), inability of patients to manage hypoglycemia (24.3%), and patients’ noncompliance to insulin regimen (24.3%). Conclusion: Despite the free of cost availability of all types of insulin, including the safest and peak less ultra-long (degludec) and long (Glargine), the availability of free of cost glucometers for all people with diabetes, the presence of a well-equipped diabetes clinic at every PHCC, the long list of guidelines and educational courses as well as an appointment system with electronic health information system (HIS), insulin inertia is a common problem among PHCPs working in Tabouk Health Region. Key words: Barriers, insulin initiation, insulin, primary health care, type 2 diabetes mellitus.

Stability Indicating Method for Known and Unknown Impurities Profiling for Vildagliptin in Vildagliptin Tablet

Background: Vildagliptin is a drug for the treatment of diabetes. DPP-IV inhibitor represents a new class of oral antihyperglycemic agents to treat patients with type 2 diabetes. Several RP-HPLC methods have been reported to determine Vildagliptin alone. However, it has been noted that there are no available stability-indicating methods in pharmacopeias (USP/BP/EP/JP) nor in the available literature to quantify known and unknown impurity patterns for vildagliptin in vildagliptin tablets. Objective: The aim of this study is to develop a new single, sensitive, robust and specific gradient RP-HPLC method to quantify known and unknown impurities and degradants of Vildagliptin in Vildagliptin tablets. Methods: Chromatographic separation has been accomplished on the Hypersil ODS column (250 x 4.6) mm, 5 μm with a mobile phase consisting of a mixture of Perchloric acid Buffer, methanol, acetonitrile and Triethylamine delivered at a flow rate of 1.0 mL minute-1 and the detection wavelength 210 nm. The developed method was validated as per ICH guidelines. Results: Vildagliptin was found degraded significantly under oxidative and alkaline stress conditions. The degradation products were well resolved from Vildagliptin and its impurities. An analytical method was found linear, accurate and precise from LOQ (Limit of Quantification) level to 150% of impurity specification limit (0.5%). Conclusion: The method found sensitive, rapid and accurate quantification of known, unknown impurities and degradants. The peak purity results confirmed that the Vildagliptin peak was homogeneous and pure in all stress samples, thus proving the stability-indicating nature of the method.

Sensitivity of DiaRem Scoring System in Predicting Type Two Diabetes Mellitus Resolution After Bariatric Surgery in Qassim Region.

Introduction: Type two diabetes mellitus (T2DM) remission has been observed as an additional benefit of bariatric surgery for morbidly obese diabetic patients. There are many scoring systems for identifying factors that predict diabetes remission; however, there is as yet no universally applicable scoring system.Aim: This study aims to test the sensitivity of the DiaRem scoring system for predicting the resolution of T2DM in morbidly obese patients who underwent bariatric surgery at King Fahad Specialist Hospital in Buraydah, Saudi Arabia.Methods: This was a non-randomized controlled trial conducted at King Fahd Specialist Hospital in Buraydah, Saudi Arabia. Visiting patients at first screening were enrolled based on eligibility criteria. Data were collected according to the given parameters such as gender, age, body mass index (BMI), duration of diabetes mellitus (DM), medications (insulin, oral antihyperglycemic agents, number of tablets if used, or no medications use), presence of comorbidities, such as hypertension and dyslipidemia, HbA1c level (before surgery and at third, sixth, and 12th months after surgery), and fasting blood glucose (FBG) level (before and after surgery).Results: A total of 96 diabetic patients were enrolled (35 males vs 61 females) with a mean age of 46.5 years. Laparoscopic sleeve gastrectomy was the most commonly performed surgery. The most common associated comorbidities were hypertension (50%) and hypothyroidism (14.6%). Results of the DiaRem scoring system showed 0-2 points in 15.6% patients, 3-7 points in 39.6% patients, 8-12 in 26% patients, 13-17 in 9.4% patients, and 18-22 in 9.4% patients. The lowest DiaRem score was associated with a higher value of BMI, shorter DM duration, and lower mean values of HbA1c and FBG post-surgery.Conclusion: Consistent with the literature, our results indicated that those with an increased BMI, shorter duration of DM, and lower values of HbA1c post-FBG had a greater chance of diabetes remission postoperatively.

The SGLT-2 Inhibitors in Personalized Therapy of Diabetes Mellitus Patients.

Diabetes mellitus (DM) represents a major public health problem, with yearly increasing prevalence. DM is considered a progressive vascular disease that develops macro and microvascular complications, with a great impact on the quality of life of diabetic patients. Over time, DM has become one of the most studied diseases; indeed, finding new pharmacological ways to control it is the main purpose of the research involved in this issue. Sodium–glucose cotransporter 2 inhibitors (SGLT-2i) are a modern drug class of glucose-lowering agents, whose use in DM patients has increased in the past few years. Besides the positive outcomes regarding glycemic control and cardiovascular protection in DM patients, SGLT-2i have also been associated with metabolic benefits, blood pressure reduction, and improved kidney function. The recent perception and understanding of SGLT-2i pathophysiological pathways place this class of drugs towards a particularized patient-centered approach, moving away from the well-known glycemic control strategy. SGLT-2i have been shown not only to reduce death from cardiovascular causes, but also to reduce the risk of stroke and heart failure hospitalization. This article aims to review and highlight the existing literature on the effects of SGLT-2i, emphasizing their role as oral antihyperglycemic agents in type 2 DM, with important cardiovascular and metabolic benefits.