Class Of Oral Antidiabetic Drugs Research Articles

Outcomes of Various Classes of Oral Antidiabetic Drugs on Nonalcoholic Fatty Liver Disease

Several oral antidiabetic drug (OAD) classes can potentially improve patient outcomes in nonalcoholic fatty liver disease (NAFLD) to varying degrees, but clinical data on which class is favored are lacking. To investigate which OAD is associated with the best patient outcomes in NAFLD and type 2 diabetes (T2D). This retrospective nonrandomized interventional cohort study used the National Health Information Database, which provided population-level data for Korea. This study involved patients with T2D and concomitant NAFLD. Receiving either sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, each combined with metformin for 80% or more of 90 consecutive days. The main outcomes were NAFLD regression assessed by the fatty liver index and composite liver-related outcome (defined as liver-related hospitalization, liver-related mortality, liver transplant, and hepatocellular carcinoma) using the Fine-Gray model regarding competing risks. In total, 80 178 patients (mean [SD] age, 58.5 [11.9] years; 43 007 [53.6%] male) were followed up for 219 941 person-years, with 4102 patients experiencing NAFLD regression. When compared with sulfonylureas, SGLT2 inhibitors (adjusted subdistribution hazard ratio [ASHR], 1.99 [95% CI, 1.75-2.27]), thiazolidinediones (ASHR, 1.70 [95% CI, 1.41-2.05]), and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.31-1.59]) were associated with NAFLD regression. SGLT2 inhibitors were associated with a higher likelihood of NAFLD regression when compared with thiazolidinediones (ASHR, 1.40 [95% CI, 1.12-1.75]) and DPP-4 inhibitors (ASHR, 1.45 [95% CI, 1.30-1.62]). Only SGLT2 inhibitors (ASHR, 0.37 [95% CI, 0.17-0.82]), not thiazolidinediones or DPP-4 inhibitors, were significantly associated with lower incidence rates of adverse liver-related outcomes when compared with sulfonylureas. The results of this cohort study suggest that physicians may lean towards prescribing SGLT2 inhibitors as the preferred OAD for individuals with NAFLD and T2D, considering their potential benefits in NAFLD regression and lower incidences of adverse liver-related outcomes. This observational study should prompt future research to determine whether prescribing practices might merit reexamination.

Drug utilization study of anti-diabetic drugs in patients attending medicine outpatient department at a tertiary care hospital in Western Maharashtra

Background: Studies on antidiabetic drug utilization are important for the optimization of drug therapy and rational prescription of drugs. The aim of the present study was to understand the trends in prescription pattern of oral anti-diabetic drugs among type 2 diabetes mellitus (T2DM) patients attending medicine outpatient department of tertiary care hospital of Western Maharashtra. Methods: A prospective observational study was conducted at Medicine OPD of Government Medical College and Hospital, Miraj. All adult patients (≥18 years) diagnosed with T2DM and willing to give informed consent to participate in the study, were enrolled. The study was approved by Institutional Ethics Committee. The data was computed using MS excel and results were expressed as counts and percentages. Results: Out of 72 T2DM patients enrolled, male population (58.33%) had higher prevalence than females (41.67%). Biguanides (63.16%) were the most commonly prescribed class of oral antidiabetic drugs followed by sulfonylureas (35.09%). Metformin (63.16%) was the most commonly prescribed oral antidiabetic drug followed by glimepiride (30.70%). Combination of oral antidiabetic drugs (OADs) were prescribed in 52.78% and 47.22% patients were prescribed single drug. ‘Metformin and glimepiride’ was the most commonly prescribed combination. Conclusions: In a chronic disease like diabetes mellitus, constant follow up for successful management is a must. It also demands active participation by the patients. Continuing education for the clinicians to keep themselves abreast of the latest development will also contribute in the effective management of diabetes mellitus and rational prescription of antidiabetic drugs.

889-P: Effectiveness of Dapagliflozin as Add-on to Metformin Alone or Metformin with Other Oral Antidiabetic Drug Classes in Type 2 Diabetes Mellitus—A Multicentre, Retrospective, Real-World Evidence Study

Background: Present real-world study evaluated the effectiveness of dapagliflozin as an add-on modality, in adult patients with T2DM. Method: We conducted an EMR-based retrospective, multicentre study in adult T2DM patients inadequately controlled on existing antidiabetic therapy and receiving dapagliflozin as add-on therapy. Baseline characteristics (visit 1) and treatment-related outcomes (visit 2 considered between 60 days-140 days after adding dapagliflozin) which included HbA1C, BMI, SBP & DBP were analyzed. Results: 3616 patients were included from 478 centres, of which 55.7% were males. Mean age was 51 years (range: 40-64 years). Most patients had received dapagliflozin + metformin + at least one other OAD [D+M+OAD, n=2907 (80.4%), 408 followed-up], while 709 patients (19.6%, 138 followed-up) received dapagliflozin + metformin (D+M). For D+M group, significant mean change was noted for all parameters at follow-up except SBP and DBP (non-significant reductions for HbA1c ≥ 8% subgroup). For D+M+OAD group, significant change was noted for all parameters at follow-up except BMI (non-significant reduction). (Table 1) Conclusion: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in real-world. Disclosure B.Sethi: None. R.K.Sahay: Advisory Panel; Torrent Pharmaceuticals Ltd, Speaker's Bureau; Novo Nordisk A/S, USV Private Limited, Intas Pharmaceuticals Ltd., Eris Lifesciences Ltd. M.H.Tiwaskar: None. R.Dhediya: None. K.Gaurav: None. R.T.Rathod: None. B.P.Kotak: Employee; Dr. Reddy's Laboratories Ltd. G.D.Dhanaki: None. S.Shah: None. Funding Dr. Reddy’s Laboratories, Ltd.

Investigation of treatment satisfaction and health-related quality of life after add-on to metformin-based therapy in patients with type 2 diabetes.

The complexity of oral antidiabetic drug (OAD) regimens affects the quality of life (QOL) and treatment satisfaction. However, data on the QOL of patients with type 2 diabetes mellitus (T2DM) receiving metformin-based OAD treatment in Asia are limited. Therefore, this study aimed to evaluate the QOL and treatment satisfaction and explore the influencing factors and their correlations among patients with T2DM receiving metformin-based OADs. This was a cross-sectional study conducted at the Outpatient Department of Metabolism and Endocrinology at a medical center in Taiwan. Data were collected using the Audit of Diabetes-Dependent Quality of Life (ADDQoL) and the Chinese version of the Satisfaction with Oral Anti-Diabetic Agent Scale (C-SOADAS) questionnaires from patients with T2DM using metformin. The outcomes were analyzed by group and stratified based on the use of two, three, and more than three OADs. The level of agreement between the questionnaires was analyzed using Spearman's rank correlation coefficient. A total of 153 patients with T2DM using metformin were included in this study. The average weighted impact score in the ADDQoL was -2.11, with no significant differences between the three groups. The C-SOADAS score showed a significant difference between the groups using two, three, and more than three OADs (21.42 [1.98] vs. 20.43 [2.09] vs. 19.00 [2.24], p < 0.0001). The ADDQoL and C-SOADAS scores showed low correlations between patients' QOL and treatment satisfaction. However, the impact of diabetes on specific aspects of life was negatively correlated with the total C-SOADAS scores. In Taiwan, a significantly greater effect on QOL was observed among patients with fewer OAD classes and higher treatment satisfaction. This study provides local evidence from self-reporting outcomes of patients with T2DM. Further studies focusing on different populations and treatment regimens for QOL are needed.

Effect of treatment intensification on glycemic control in patients with subcontrolled type 2 diabetes who failed on two oral antidiabetic agents

AimsTreatment intensification (TI) may help patients with type 2 diabetes mellitus (T2DM) achieve target hemoglobin A1c (A1c) < 7.0%. This study aimed to measure the influence of TI on A1c outcome in patients who insufficiently responded to two classes of oral antidiabetic drugs (2OADs). Materials and methodsA retrospective observational study of patients with T2DM was performed using health plan claims and A1c records accrued between January 2010 and March 2017. The study population had an A1c ≥ 7.0% (baseline A1c) after treatment with 2OADs for one year. Patients who had TI with a third-class antidiabetic agent, including basal/biphasic insulin, glucagon-like peptide-1 receptor agonists (GLP-1RA), or OAD, within 365 days after baseline A1c were included. Patients who did not receive TI (NTI) within one year from the suboptimal A1c control were matched with TI patients using a propensity score approach. The odds ratio of achieving an A1c < 9.0% and < 7.0% for TI vs. NTI were calculated by logistic regressions. ResultsA1c values of 401 TI − NTI matched pairs were analyzed. TI patients achieved a significantly lower follow-up A1c than NTI patients (7.79% ± 1.45 vs. 8.02% ± 1.67, p = 0.03). The odds ratio [95% confidence interval] of achieving A1c < 9.0% and < 7.0% for TI was 1.50 [1.04−2.17] and 1.19 [0.87−1.63], respectively. ConclusionTI with a third-class agent further reduced A1c levels in patients whose A1c insufficiently responded with 2OADs; however, most patients failed to achieve an A1c < 7.0% on the intensified treatment.

From Kidney Protection to Stroke Prevention: The Potential Role of Sodium Glucose Cotransporter-2 Inhibitors.

Chronic kidney disease (CKD) is an independent risk factor for stroke and covert cerebrovascular disease, and up to 40% of stroke patients have concomitant CKD. However, the so-called "cerebrorenal interaction" attracted less attention compared to its cardiorenal counterpart. Diabetes is the leading cause of CKD. The sodium-glucose cotransporter (SGLT) 2 inhibitor is a relatively new class of oral anti-diabetic drugs and has cardiorenal benefits in addition to glucose-lowering effects. In the present perspective, we would like to review the current status and future potential of the SGLT2 inhibitor in cerebro-renal interactions and strokes regardless of the status of diabetes. We propose the potential roles of baseline renal functions and SGLT1/2 dual inhibition in stroke prevention, as well as the additional benefits of reducing atrial fibrillation and hemorrhagic stroke for SGLT2 inhibitors. Further clinical trials are anticipated to test whether SGLT2 inhibitors can fulfill the long-standing unmet clinical need and stop such a vicious cycle of cerebro-renal interaction.

Treatment patterns and satisfaction in patients with type 2 diabetes newly initiating oral monotherapy with antidiabetic drugs in Japan: results from the prospective Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND)

IntroductionTo present longitudinal data from the Real-world Observational Study on Patient Outcomes in Diabetes (RESPOND) in Japan.Research design and methodsIn this multicenter, prospective, observational cohort study, patients with type 2...

A 5-year trend in the use of sodium-glucose co-transporter 2 inhibitors and other oral antidiabetic drugs in a Middle Eastern country

BackgroundSodium glucose co-transporter 2 inhibitors (SGLT2is) are a novel class of oral antidiabetic drugs. To date, there are no pharmacoepidemiologic studies investigating the pattern of use of SGLT2is compared to other oral antidiabetic drugs in the Middle East, including Qatar.AimThis study aimed to explore the trends in the use of SGLT2is compared to other oral antidiabetic drugs in Qatar from 2016 to 2020.MethodThis is a descriptive, retrospective cross-sectional study where information on all oral antidiabetic drugs dispensed as in- or out-patient prescriptions from 2016 to 2020 in Hamad Medical Corporation hospitals, Qatar were collected. Outcomes included the number and relative frequency of quarterly prescriptions of different oral antidiabetic drug classes [biguanides, sulfonylureas, dipeptidyl peptidase 4 inhibitors, thiazolidinediones, meglitinides, α-glucosidase inhibitors, and SGLT2is] prescribed from 2016 to 2020.ResultsSGLT2is prescriptions increased from 1045 (2.13%) in 2017 to 8375 (12.39%) in 2020, while sulfonylureas prescriptions declined from 10,436 (21.25%) to 9158 (13.55%) during the same period. Metformin use decreased from 23,926 (48.71%) in 2017 to 30,886 (45.70%) in 2020. The proportions of thiazolidinediones, meglitinides, α-glucosidase inhibitors prescriptions remained stable over the years. Among SGLT2is, empagliflozin prescriptions showed an increase from 537 (10.65%) to 2881 (34.40%) compared to dapagliflozin, which decreased by the end of 2018 from 4505 (89.35%) to 5494 (65.6%).ConclusionSGLT2is have largely replaced sulfonylureas in Qatar. The increasing trend in their use over the years is similar to that reported in other countries. The trend among SGLT2is suggests greater preference for empagliflozin over dapagliflozin.

Sodium-Glucose Cotransporter Inhibitors as Antidiabetic Drugs: Current Development and Future Perspectives.

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (gliflozins) represent the most recently approved class of oral antidiabetic drugs. SGLT-2 overexpression in diabetic patients contributes significantly to hyperglycemia and related complications. Therefore, SGLT-2 became a highly interesting therapeutic target, culminating in the approval for clinical use of dapagliflozin and analogues in the past decade. Gliflozins improve glycemic control through a novel insulin-independent mechanism of action and, moreover, exhibit significant cardiorenal protective effects in both diabetic and nondiabetic subjects. Therefore, gliflozins have received increasing attention, prompting extensive structure-activity relationship studies and optimization approaches. The discovery that intestinal SGLT-1 inhibition can provide a novel opportunity to control hyperglycemia, through a multifactorial mechanism, recently encouraged the design of low adsorbable inhibitors selectively directed to the intestinal SGLT-1 subtype as well as of dual SGLT-1/SGLT-2 inhibitors, representing a compelling strategy to identify new antidiabetic drug candidates.

SGLT2 Inhibitors for Nephrologists

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are the mainstay of therapy for the prevention of progressive renal damage in diabetic and non-diabetic kidney diseases, especially glomerulonephritides. Sodium-glucose co-transporter-2 inhibitors are a relatively new class of oral antidiabetic drugs. Early evidence suggests that there are renal and cardiovascular benefits of this class of drugs that extend beyond glycaemic control for patients both with and without diabetes. With each and every trial, the limit for the glomerular filtration rate has been set lower, making the drugs more suitable from the perspective of nephrologists. This drug class has the potential to become the mainstay of reno-protective strategies used by nephrologists, in addition to angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. This article reviews the evidence and reports that are already published regarding the use of sodium-glucose co-transporter-2 inhibitors to treat non-diabetic glomerular disease.

Knowledge and practice of community pharmacists towards SGLT2 inhibitors.

Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists' knowledge and practice towards SGLT2 inhibitors. Thus, improving pharmacists' knowledge about this group of medications could improve the treatment outcome of people with diabetes. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists' experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists' dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients' outcome; thus, continuous education for the pharmacists is essential.

Knowledge and practice of community pharmacists towards SGLT2 inhibitors

Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists’ knowledge and practice towards SGLT2 inhibitors. Thus, improving pharmacists’ knowledge about this group of medications could improve the treatment outcome of people with diabetes. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists’ experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists’ dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients’ outcome; thus, continuous education for the pharmacists is essential.

Knowledge and practice of community pharmacists towards SGLT2 inhibitors

Background: Sodium/glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic drugs which improve glycaemic control in type 2 diabetes mellitus (T2DM) by preventing the kidney from reabsorbing glucose back to blood. Community pharmacists have long-term relationships with most of their chronic patients, so they play a key role in care for people with diabetes. Therefore, the objective of this study was to assess pharmacists' knowledge and practice towards SGLT2 inhibitors. Methods: A cross-sectional study was conducted to meet the study objectives. A convenience sample of 348 community pharmacists in Jordan was recruited. knowledge and practice were assessed using a self-administered questionnaire created for the purpose of this study. Results: A total of 400 community pharmacists were reached, of whom 348 answered the survey (response rate 87%). The results indicated that SGLT2 inhibitors knowledge score among community pharmacists in Jordan was 6.61 (out of 12). Factors like age, gender, location of the pharmacy, years of pharmacists' experience had no effect on knowledge score; however, pharmacists who attended training courses on diabetes had higher knowledge scores. Additionally, pharmacists' dispensing practice toward SGLT2 inhibitors had insufficient knowledge, such as lack of knowledge about the superiority of SGLT2 inhibitors over other anti-diabetics and inability to give the best advice to patients. Conclusions: Our findings reflect a moderate knowledge among community pharmacists about SGLT2 inhibitors which may negatively affect the patients' outcome; thus, continuous education for the pharmacists is essential.

Association of Dulaglutide Initiation Timing With Treatment Patterns and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus in the United States

PurposeTo describe clinical characteristics and treatment outcomes for early or late initiation of dulaglutide therapy in patients with type 2 diabetes. MethodsThis retrospective, claims-based analysis evaluated adults with type 2 diabetes, ≥1 claim for dulaglutide 0.75 mg or 1.5 mg once-weekly injection (between November 2014 and August 2019), and no prior use of glucagon-like peptide 1 receptor agonists or insulin. Cohorts were defined based on the number of oral antidiabetic drug (OAD) classes used within the 24-month baseline period before dulaglutide therapy initiation: 1 OAD, 2 OADs, or ≥3 OADs. The number of OAD classes used before dulaglutide therapy initiation served as a proxy for timing of initiation, with a higher number of OAD classes indicating a longer duration of T2D. Baseline demographic and clinical characteristics were compared across each cohort. Six-month follow-up outcomes, including change in glycosylated hemoglobin (HbA1c) and treatment patterns, were descriptively assessed within each cohort. FindingsThe study population consisted of 18,121 patients across the 1 OAD (n = 4822), 2 OADs (n = 6293), and ≥3 OADs (n = 7006) cohorts. Mean age at baseline was 54.7 years. Males were more prevalent in the ≥3 OADs cohort. Most patients (67%–70%) initiated treatment with dulaglutide 0.75 mg. Dose escalation to 1.5 mg was uncommon (15%–20%) but trended higher in the ≥3 OAD cohort. Adherence to dulaglutide at 6-month follow-up (61%–67%) increased with higher baseline OAD use. The HbA1c assessment (n = 3178) included 761 patients in the 1 OAD cohort, 1088 patients in the 2 OADs cohort, and 1329 patients in the ≥3 OADs cohort. Baseline mean [SD] HbA1c level increased with number of OAD classes (1 OAD: 8.18% [1.80]; 2 OADs: 8.56% [1.66]; and ≥3 OADs: 8.73% [1.51]). Patients in the early dulaglutide therapy initiator group experienced larger reductions in HbA1c levels (1 OAD: −1.39%; 95% CI, −1.50 to −1.27; 2 OADs: −1.30%; 95% CI, −1.39 to −1.20; and ≥3 OADs: −1.01%; 95% CI, −1.09 to −0.93) versus the patients in the delayed initiator group. Patients in the early dulaglutide therapy initiator group also achieved HbA1c <7% at 6-month follow-up more frequently than those in the later initiator group (1 OAD: 68%; 2 OADs: 51%; and ≥3 OADs: 33%). ImplicationsCohorts of dulaglutide therapy initiators, defined by prior OAD use as a proxy of timing of initiation, differed in their baseline characteristics and short-term follow-up outcomes. Earlier dulaglutide therapy initiation was associated with lower mean HbA1c levels and increased probability of achievement of HbA1c <7% during the 6-month follow-up period.

A Review of Economic Models Submitted to NICE's Technology Appraisal Programme, for Treatments of T1DM & T2DM.

Background: In the UK, 4.7 million people are currently living with diabetes. This is projected to increase to 5 million by 2025. The direct and indirect costs of T1DM and T2DM are rising, and direct costs already account for approximately 10% of the National Health Service (NHS) budget. Objective: The aim of this review is to assess the economic models used in the context of NICE’s Technology Appraisals (TA) Programme of T1DM and T2DM treatments, as well as to examine their compliance with the American Diabetes Association’s (ADA) guidelines on computer modelling. Methods: A review of the economic models used in NICE’s TA programme of T1DM and T2DM treatments was undertaken. Relevant TAs were identified through searching the NICE website for published appraisals completed up to April 2021. The review also examined the associated Evidence Review Group (ERG) reports and Final Appraisal Documents (FAD), which are publicly accessible. ERG reports were scrutinised to identify major issues pertaining to the economic modelling. The FAD documents were then examined to assess how these issues reflected on NICE recommendations. Results: Overall, 10 TAs pertaining to treatments of T1DM and T2DM were identified. Two TAs were excluded as they did not use economic models. Seven of the 8 included TAs related to a novel class of oral antidiabetic drugs (OADs), gliflozins, and one to continuous subcutaneous insulin infusion (CSII) devices. There is a lack of recent, robust data informing risk equations to enable the derivation of transition probabilities. Despite uncertainty surrounding its clinical relevance, bodyweight/BMI is a key driver in many T2DM-models. HbA1c’s reliability as a predictor of hard outcomes is uncertain, chiefly for macrovascular complications. The external validity of T1DM is even less clear. There is an inevitable trade-off between the sophistication of models’ design, their transparency and practicality. Conclusion: Economic models are essential tools to support decision-making in relation to market access and ascertain diabetes technologies’ cost effectiveness. However, key structural and methodological issues exist. Models’ shortcomings should be acknowledged and contextualised within the framework of technology appraisals. Diabetes medications and other technologies should also be subject to regular and consistent re-appraisal to inform disinvestment decisions. Artificial intelligence could potentially enhance models’ transparency and practicality.

Use of oral anti-diabetic drugs and risk of hospital and intensive care unit admissions for infections

BackgroundSepsis is one of the leading causes of hospital mortality, and diabetes is a risk factor for the development of infections. Although strong evidence has shown an association between metformin and reduced risk of infections, the risk of developing infections with newer classes of oral anti-diabetic drugs (OADs) has been less certain. Our study aims to examine the association between outpatient OAD use and hospital admissions for infections. MethodsThe study cohort included 1.39 million adults with diabetes utilizing the Veterans Health Affairs Corporate Data Warehouse. Multivariate logistic regression was used to estimate the effect of each drug class on hospital admission for infection while adjusting for covariates. ResultsAfter adjusting for covariates, those who took metformin during the study period had 3.3% lower odds of hospital admission for infection compared to those who were never on metformin (OR 0.97, 95% CI 0.95-0.98). OADs that were associated with a statistically significant increased odds of being admitted included meglitinides (OR 1.22, 95% CI 1.07-1.38), SGLT2 inhibitors (OR 1.16, 95% CI 1.08-1.24), alpha-glucosidase inhibitors (OR 1.09, 95% CI 1.04-1.15), and DPP4 inhibitors (OR 1.04, 95% CI 1.01-1.06). ConclusionsMetformin was associated with lower odds of hospital admission for infection while meglitinides, SGLT2 inhibitors, alpha-glucosidase inhibitors, and DPP4 inhibitors were associated with higher odds of admission for infection.

SGLT-2 INHIBITORS – AN ANTIDIABETIC WITH CARDIOPROTECTIVE EFFECTS

Today, global healthcare possesses a tremendous burden due to the increasing prevalence of Type 2 diabetes mellitus (T2DM) that has reached pandemic proportions. The chronic disease of T2DM causes macrovascular and/or microvascular pathologic changes, resulting in increased risk for the development of myocardial infarction, heart failure, stroke, renal failure, and reduced survival. This chronic condition also presents signicant interactions between T2DM, heart failure, and renal dysfunction, forming vicious circles, and the interruption of these circles represents important therapeutic goals. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), a new drug class of oral antidiabetic drugs (OADs), approved for the treatment of diabetes, have been shown to exert a favorable metabolic prole help in a signicant reduction in the atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. This minireview will provide a valuable tool for understanding the vicious circle and demonstrating the expanding role of SGLT2 inhibitors critical for cardiologists, diabetologists, nephrologists, and primary care physicians familiar with this drug class.

Genetic Association of Solute Carrier Transporter Gene Variants with Metformin Response.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated blood glucose levels and is influenced by both genetic and environmental factors. It is treated with various classes of oral antidiabetic drugs, however, response to treatment is highly variable with patients failing to achieve adequate glycemic control. Treatment response variability has been associated with single nucleotide polymorphisms (SNPs) which influence the pharma-cokinetics and pharmacodynamics of drug(s). The aim of this study was to evaluate the genetic association of 17 SNPs and the response to metformin therapy in patients diagnosed with diabetes from the indigenous Nguni population of South Africa. One hundred and forty indigenous African patients diagnosed with T2DM were recruited and genotyped using the MassARRAY® system. Therapeutic response of patients was ascertained by a change in Hb A1c. Two SNPs (rs1801282 and rs6265) were monomorphic. All other variants were within the Hardy-Weinberg equilibrium (HWE). The T allele of the SLC variant rs316009 [odds ratio (OR) = 0.25, 95% confidence interval (95% CI) = 0.01-0.09, p value = 0.044] and the CT genotype of the PCK1 variant rs4810083 (OR = 2.80, 95% CI = 1.01-7.79, p value = 0.049) were associated with an improved response to treatment after adjustment. No association was observed with post Bonferroni correction. Moreover, this study provides important additional data regarding possible associations between genetic variants and metformin therapy outcomes. In addition, this is one of the first studies providing genetic data from the understudied indigenous sub-Saharan African populations.

A Case of Euglycemic Diabetic Ketoacidosis Following Canagliflozin Therapy

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes mellitus (DM). In general, DKA characterized by blood sugar over 250 mg/dL, anion-gap metabolic acidosis, and increased plasma or urine ketones. Approximately 2–3% of DKA patients can present with normal blood glucose levels (less than 250 mg/dl) which called euglycemic DKA. Some of the etiologies of euglycemic DKA include recent use of insulin, low caloric intake, alcoholism, chronic liver disease, and pregnancy. Very rarely, SGLT2 inhibitor use may be responsible for euglycemic DKA. Case Presentation: Here we present a case of 44 years old female with a past medical history of DM type 2 who presented with acute onset of nausea and vomiting. Initial laboratory findings were remarkable for anion gap metabolic acidosis with a blood glucose level of 201 mg/dl. The patient was on long-acting insulin along with Canagliflozin and Metformin therapy over years and reported being compliant with medications. She was treated with intravenous insulin therapy which resolved acidosis as well as symptoms. The patient was discharged with recommendations of discontinuation of Canagliflozin. Discussion: SGLT2 inhibitors are the novel class of oral antidiabetic drugs which widely used due to their favorable cardiovascular and renal outcomes independent of glycemic control. However, their side effects remain a concern. DKA is a rare but serious side effect of SGLT2 inhibitors with an incidence rate of 9.4% in type 1 DM and less than 0.2% in type 2 DM. Patients typically present with euglycemia or low-grade hyperglycemia which results in a diagnostic challenge for treating physicians. SGLT2 inhibitors increase urinary glucose excretion with a subsequent decrease in circulating insulin and an increase in glucagon, rendering a metabolic shift from glucose to fatty acid utilization. During times of intercurrent illness (decreased oral intake, sepsis) or metabolic stress (surgery), decreased carbohydrate intake coupled with the aforementioned changes will result in decreased insulin secretion and increased counter-regulatory hormones including adrenaline and cortisol, promoting lipolysis, fatty acid oxidation, and ketone production by the liver which ultimately leading to euglycemic DKA. Conclusion: SGLT2 inhibitors induced euglycemic DKA treatment is identical to classic DKA with consideration of the lack of hyperglycemia. Appropriate patient counseling to ensure safe SGLT2 inhibitor therapy is crucial, including appropriate holding parameters during concomitant volume-depleting illnesses and decreased oral intake. Timely diagnosis of euglycemic DKA, and recognitions of other rare but lethal side effects to decrease overall morbidity and mortality.

Effects of sitagliptin on ß-adrenoceptor mediated relaxation in streptozotocin-diabetic rat aorta

Background/aim Dipeptidyl peptidase-4 (DPP4) inhibitors, a class of oral antidiabetic drugs, have been shown to be protective on the vascular system because of their antiinflammatory, antiatherosclerotic, and vasodilatory effects. ß 2-adrenoceptors (ß 2-ARs) mediate the vasorelaxation in the aorta. However, ß 3-adrenoceptor-mediated relaxation has not been studied in diabetic aorta yet. Thus, we aimed to study the effect of sitagliptin treatment on ß 2- and ß3-adrenoceptor-mediated relaxations in the diabetic rat aorta.Materials and methods Eight-week old Sprague Dawley rats were divided into three groups: control, diabetic, sitagliptin treated diabetic. Diabetes was induced by injection of streptozotocin (35 or 40 mg/kg, intraperitoneally). After 10 weeks of diabetes, some of the diabetic rats were treated with sitagliptin (orally, 10mg/kg/day). ß2- and ß 3-AR-mediated relaxation responses were evaluated by using isoprenaline and CL 316,243, respectively. ß3-AR-mediated relaxation experiments were repeated in presence of L-NAME. Western blotting and immunohistochemistry were performed to determine the abundance of ß3-adrenoceptor and endothelial nitric oxide synthase (eNOS).Results The isoprenaline-mediated relaxation response was impaired in the diabetic group and sitagliptin treatment did not improve it. There was no significant change in CL316,243 mediated-relaxation or protein expression of ß 3-ARs among the groups. However, the ratio of phosphorylated eNOS/NOS protein was increased markedly in the sitagliptin treated group, which points the stimulating effect of this drug towards the eNOS pathway. Conclusion Our results indicate that sitagliptin treatment does not alter ß- AR-mediated relaxation in streptozotocin-diabetic rat aorta; however, it significantly stimulates the eNOS pathway. Future studies are needed to clarify the relationship between the eNOS pathway and DPP-4 inhibition.