Use Of Oral Hypoglycemic Agents Research Articles

Risk factors for abdominal aortic aneurysm in patients with diabetes

ObjectiveAlthough diabetes has been shown to be negatively associated with development of abdominal aortic aneurysm (AAA), patients with diabetes may still develop aneurysms. In this study, we examined risk factors for the development of AAA in patients with diabetes. MethodsAdults >50 years of age with diabetes who underwent health screening between 2009 and 2012 were followed for incident AAA until December 31, 2019. Cox proportional hazard regression models were used to calculate multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk factors associated with AAA. ResultsAmong 1,913,066 participants (55.3% men), 6996 AAA cases were identified during a mean follow-up of 7.7 years. Increased AAA risk was observed for age ≥65 years (HR, 2.69; 95% CI, 2.55-2.83), men (HR, 1.81; 95% CI, 1.69-1.94), smoking (former smoker ≥20 pack-years [PY]; HR, 1.75; 95% CI, 1.61-1.89; current smoker <20 PY; HR, 1.76; 95% CI, 1.59-1.94; current smoker ≥20 PY; HR, 2.40; 95% CI, 2.23-2.59), abdominal obesity (HR, 1.30; 95% CI, 1.23-1.38), and comorbidities, including hypertension (HR, 1.63; 95% CI, 1.53-1.73), dyslipidemia (HR, 1.35; 95% CI, 1.29-1.42), chronic kidney disease (HR, 1.52; 95% CI, 1.44-1.61), and cardiovascular disease (HR, 1.71; 95% CI, 1.58-1.86). Heavy (HR, 0.67; 95% CI, 0.61-0.74) and mild alcohol consumption (HR, 0.78; 95% CI, 0.74-0.83), overweight (HR, 0.87; 95% CI, 0.81-0.93) and obesity (HR, 0.81; 95% CI, 0.75-0.87), longer diabetes duration (≥5 years: HR, 0.74; 95% CI, 0.70-0.78), and using three or more oral hypoglycemic agents (OHA) (HR, 0.84; 95% CI, 0.79-0.90) were associated with decreased AAA risk, whereas insulin use was associated with a marginally increased risk (HR, 1.09; 95% CI, 1.00-1.18). Among the OHAs, metformin (HR, 0.95; 95% CI, 0.90-1.00), thiazolidinediones (HR, 0.87; 95% CI, 0.79-0.97), and sulfonylureas (HR, 0.88; 95% CI, 0.83-0.93) were associated with a decreased risk of AAA. ConclusionsAlthough diabetes is associated with decreased AAA risk, those with comorbid cardiometabolic diseases, abdominal obesity, and a smoking history should be aware of an increased AAA risk. Further studies are warranted to verify the potential use of OHAs for decreasing AAA risk.

Abstract #1406118: Improving Inpatient Diabetes Management in a Community Hospital: A Resident-Run Quality Improvement Initiative

Diabetes mellitus is one of the most encountered co-morbidities in outpatient and inpatient settings. Treatment varies from oral hypoglycemic agents (OHAs) to injectable agents to insulin based on average glucose levels. Guidelines recommend discontinuation of OHAs during inpatient hospitalization and using long and short-acting insulin as treatment, to avoid unpredictable glucose levels. In our community hospital, it was noted that if home OHAs are discontinued on admission, physicians tend to use only the insulin sliding scale (ISS) or short-acting pre-prandial and bedtime insulin as treatment. Recent studies have shown that stand-alone ISS is inferior to a basal/bolus insulin regimen in achieving adequate blood glucose control in hospitalized patients. Our aim is to improve blood glucose control in our community hospital by implementing an insulin policy as a standard treatment for diabetes management. We used the Institute Healthcare Improvement (IHI) model to guide our quality improvement (QI) project. Root cause analysis through a fishbone revealed contributing factors. A multidisciplinary team, which included IT, pharmacy, and resident physicians, was created to implement the proposed solutions. Several PDSA cycles were used to test changes. Despite guidelines to assist in the management of inpatient diabetes, our hospital lacked a standard approach. PDSA 1 involved education about guidelines, discontinuation of OHAs, and utilizing insulin for management. Post-implementation, >50% of physicians still ordered OHAs. PDSA 2 cycle, a pharmacy checkpoint was placed to discontinue OHAs, and physicians were prompted to use insulin. This led to the elimination of OHAs and the initiation of insulin. However, stand-alone ISS was being used, causing hyperglycemia. PDSA 3 re-education was provided. Policy changes were implemented to incorporate a basal insulin regimen along with ISS for inpatient management. We proposed 10 units of long-acting insulin plus ISS. The new policy was implemented with the aid of the pharmacy. A review of post-intervention data from 250 patients through a 6-month period showed that OHAs were continued in only 1.2% of the patients. Stand-alone ISS therapy was started in 24% of the patients, whereas 62% of patients received a combination of basal insulin along ISS. We noted hypoglycemic events (glucose <60 mg/dl) in 7.6% of the patients, and hyperglycemia (glucose >160 mg/dl) in 60% of the patients. Limiting the use of OHAs in the hospital resulted in fewer hypoglycemic episodes. Prior to our QI, we noted an inconsistent approach to diabetes management leading to hypo and severe hyperglycemic events. As a part of this QI initiative, a new hospital-wide policy, which included basal and short-acting insulin, was incorporated with the help of a multidisciplinary team. We noticed that incorporating a standardized approach led to an improved trend in glucose control and fewer complications secondary to severe hyperglycemia or hypoglycemia.

Electrocardiographic changes associated with SGLT2 inhibitors and non-SGLT2 inhibitors: A multi-center retrospective study.

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors has been shown with cardiovascular benefit in type 2 diabetes mellitus (T2DM) patients. However, its osmotic diuresis still concern physicians who may look for possible electrolyte imbalance. We therefore aimed to investigate electrocardiographic (ECG) changes associated with SGLT2 inhibitors.MethodsElectronic medical records from Chang Gung Research Database between January 1, 2001 and January 31, 2019 were searched for patients with ECG reports and patients on an oral hypoglycemic agent (OHA). We then separate these T2DM patients with EKG into those taking either SGLT2 inhibitors or non-SGLT2 inhibitors. We excluded patients with OHA use <28 days, age <18 years, baseline ECG QTc > 500 ms, and ECG showing atrial fibrillation or atrial flutter. Propensity score matching (PSM) was performed between groups by age, sex, comorbidities, and medications (including QT prolonging medications). Conditional logistic regression and Firth's logistic regression for rare events were employed to compare the difference between SGLT2 and non-SGLT2 inhibitor patients.ResultsAfter exclusion criteria and PSM, there remained 1,056 patients with ECG on SGLT2 inhibitors and 2,119 patients with ECG on non-SGLT2 inhibitors in the study. There were no differences in PR intervals, QT prolongations by Bazett's or Fridericia's formulas, new onset ST-T changes, new onset CRBBB or CLBBB, and ventricular arrhythmia between the group of patients on SGLT2 inhibitors and the group of patients on non-SGLT2 inhibitors. There were no differences between the two groups in terms of cardiovascular death and sudden cardiac death. In addition, there were no differences between the two groups in terms of electrolytes.ConclusionsCompared with T2DM patients on non-SGLT2 inhibitors, there were no differences in PR interval, QT interval, ST-T changes, bundle-branch block, or ventricular arrhythmia in the patients on SGLT2 inhibitors. There were no differences in cardiovascular mortality between these two groups. In addition, there were no electrolyte differences between groups. SGLT2 inhibitors appeared to be well-tolerated in terms of cardiovascular safety.

Evaluation of hypoglycemic therapeutics and nutritional supplementation for type 2 diabetes mellitus management: An insight on molecular approaches.

This review aims to summarize the current management of type 2 diabetes principles, including oral hypoglycemic agents, types of insulin administration, diet maintenance, and various molecular approaches. A literature search was conducted in different databases such as Scopus, ScienceDirect, Google Scholar, and Web of Science by using the following keywords: type-2 diabetes mellitus (T2DM), first-line and second-line treatment, oral hypoglycemic agents, insulin administration, diet/nutritional therapy, gene and stem cell therapy, and diabetic complications. The first-line treatment of T2DM includes administering oral hypoglycemic agents (OHAs) and second-line treatment by insulin therapy and some OHAs like Sulfonylurea's (SU). The oral hypoglycemic or oral antidiabetic drugs have the function of lowering glucose in the blood. Insulin therapy is recommended for people with A1C levels > 7.0, and insulin administration is evolved drastically from the syringe, pump, pen, inhalation, insulin jet, and patch. The use of OHAs and insulin therapy during glycemic control has a severe effect on weight gain and other side effects. Hence, diet maintenance (macro and micronutrients) and nutritional therapy guidelines were also reviewed/recommended for safe T2DM management. Besides, the recent progress in molecular approaches that focuses on identifying new targets for T2DM (i.e.) consisting of gene therapy, stem cell therapy, and the modulation of insulin signaling pathwaysfor the regulation of glucose storage and uptake also discussed. The analysis of all these key factors is necessary to develop a potential agent to cure T2DM and suggest that a combination of therapies will pave the way for advanced management of T2DM.

762-P: Use of Oral Hypoglycemic Agents in Type 1 DM

Obesity prevalence in T1DM is increasing. While T1DM is typically treated exclusively with insulin, the changing obesity trends and T1DM heterogeneity has raised interest in use of various oral hypoglycemic agents (OHA) as adjunctive therapy. The extent and impact of OHA “off label” use in “real world” settings is not well studied. We report on the extent, distribution, glycemic and cardiometabolic impact of OHA use in a T1DM cohort. Retrospective chart review of 300 patients with health record coded T1DM seen between January 2015 and January 2018 was done. OHA use, comorbidities, demographics, vital signs, and cardiometabolic risk surrogates were extracted for analyses.. The chart review showed actual DM subtypes were :163 (54%) T1DM, 43 (14.3%) Latent Autoimmune Diabetes of Aging (LADA), 1 (0.3%) maturity-onset diabetes of the young, 2 (0.7%) type 1.5 (essentially LADA), 8 (2.7%) type 1+2 (T1DM with obesity and insulin resistance), 11 (3.7%) deceased, and 71 (23.7%) T2DM that had been miscoded as T1DM. All subsequent analyses included T1DM, LADA, type 1.5, and type 1+2 in the verified T1DM cohort. 16% of the T1DM cohort were on at least one OHA and most common were sulphonylureas (16%), DPP-4 blockers (15.3%), SGLT-2 blockers (11%) and metformin (9.2%). OHA use in T1DM was not associated with any significant change in weight, BMI nor blood pressure. There was however a statistically significant decline in total cholesterol, LDL and HBA1c but not fasting triglycerides. No significant differences were found in hypoglycemia related admissions or DKA admissions with OHA use including among SGLT-2 users. Off label use of OHAs is quite prevalent in the studied population of patients with T1DM (16%) and their use was associated with improvements in HBA1c and aspects of lipid metabolism despite no significant changes in weight, BMI or blood pressure. OHAs may have utility as adjunctive therapy and require more structured study to enable development of therapeutic algorithms for their use in T1DM therapeutics. Disclosure K. G. Romo: None. W. A. West: None. G. I. Uwaifo: None.

Adverse Effects of Oral Hypoglycemic Agents and Adherence to them among Patients with Type 2 Diabetes Mellitus in Nepal

Introduction: Oral hypoglycemic agents (OHAs) are the most common drugs used in Type 2 Diabetes Mellitus. There are various established adverse effects related to their use including hypoglycemia, weight gain, gastrointestinal disturbance, lactic acidosis, and fluid retention. However, the pattern of adverse effects related to OHAs in Nepalese patients still needs to be explored. Our study aims to determine the pattern of adverse effects resulting from the use of OHAs among Type 2 Diabetes mellitus patients and their adherence to the medication.&#x0D; Methods: All diabetic patients who met the inclusion criteria were enrolled in the study. After informed consent, patients were interviewed and evaluated as per the designed proforma. They were mainly studied for common drug used, adverse effects of the drugs, occurrence of hypoglycemia, and adherence to treatment.&#x0D; Results: The study comprised of 183 patients with mean age of 58.73 years (SD = 12.95). Fifty-six (30.6%) patients said that they developed adverse effects of drugs but only 21 (11.5%) of them reported to their treating physician. Most common adverse effect were related to central nervous system such as tingling sensation of hands and feet, dizziness, drowsiness, etc. Though 91 (49.7%) patients had developed symptoms suggestive of hypoglycemia, only 31 (16.9%) knew that it was due to hypoglycemia. Majority of the patients (n = 143, 78.1%) administered the drugs as prescribed by the physician. Among the defaulters, the most important reasons for failure to properly administer the drugs was forgetfulness in 82.5% (n = 33, N = 40) of cases. Among the study variables family history of chronic illness (p = 0.046) and information about adverse effects from physician (p = 0.001) had a significant relationship with incidence of adverse effects. Whereas none of them had a significant relationship with adherence to hypoglycemic medication.&#x0D; Conclusion: The incidence of adverse effects was high with hypoglycemia occurring in 49.7% of the cases, though only one-third of them recognized it to be due to hypoglycemia, in the patients with Type 2 Diabetes Mellitus. Family history of chronic illness and information about adverse effects from the physician had significant relationship with the incidence of adverse effects of hypoglycemic treatment.

Use of pharmacy dispensing data to measure adherence and identify nonadherence with oral hypoglycemic agents

PurposeA framework for calculation of adherence for oral hypoglycemic agents (OHAs) based on data from health-insurance claims is available. Pharmacy dispensing data aid identification of nonadherent patients in pharmacy practices. However, use of these data for calculation of OHA adherence requires additional methodological categories. We examined the impact of different methodological choices on estimation of OHA adherence using pharmacy dispensing data.MethodsFour methodological categories were added to the framework available to be used for adherence calculation with pharmacy dispensing data. Three adherence measures were defined to supply pharmacists with significant information on OHA use of their patients: (i) percentage of days covered by use periods of dispensed medication (PDC), (ii) mean rate of adherent patients with a PDC ≥80 % (MRAP80), and (iii) mean number of nonadherent patients (MNNP80) per pharmacy with a PDC <80 %. A basic scenario was developed from 16 methodological categories. Consequences of choices for different parameters within these categories on the scores of the three adherence measures were calculated from dispensing data between July 2013 and July 2014.ResultsData were available for 604,500 OHA users in 1737 community pharmacies in the Netherlands. For the basic scenario, mean PDC for OHA was 88.3 %. MRAP80 was 80.3 %, which corresponded to an average of 69 nonadherent patients per pharmacy. Different choices for parameter values resulted in score variations for PDC of 85.0–91.8 %, for MRAP80 of 75.3–86.1 %, and between 49 and 92 MNNP80 per pharmacy.ConclusionSixteen methodological categories specified calculation of OHA adherence based on pharmacy dispensing data. Adherence scores expressed as percentages were relatively robust to variation in parameter values, but differed substantially for the absolute numbers of nonadherent patients per pharmacy.

Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors.

BackgroundThe role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).MethodsWe analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations.ResultsGV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (β=0.209, P=0.009) and MAG (β=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk.ConclusionGV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus & occurrence of osteoporosis.

Background & objectives:Type 2 diabetes mellitus (T2DM) is considered to be a protective factor against development of osteoporosis. But oral hypoglycaemic agents (OHA) are likely to increase the risk of osteoporosis. This study was carried out to evaluate the effect of various OHA on bone mineral density (BMD) in patients with T2DM.Methods:Forty one patients (study group) with T2DM (mean age 51.9±5.5 yr; 31 females) receiving treatment with oral hypoglycaemic agents (OHA) [thiazolidinediones alone (n=14) or in combination with other OHA (n=27)] for a period of at least three consecutive years and 41 age- and gender-matched healthy controls (mean age 51.4±5.1 yr) were included in the study. A detailed clinical history was taken and all were subjected to physical examination and recording of anthropometric data. BMD was assessed for both patients and controls.Results:The mean body mass index (kg/m2) (26.5±4.90 vs 27.3 ±5.33) and median [inter-quartile range (IQR)] duration of menopause (yr) among women [6(2-12) vs 6(1-13)] were comparable between both groups. The bone mineral density (BMD; g/cm2) at the level of neck of femur (NOF) (0.761±0.112 vs 0.762±0.110), lumbar spine antero-posterior view (LSAP) (0.849±0.127 vs 0.854±0.135); median Z-score NOF {0.100[(-0.850)-(0.550)] vs -0.200[(-0.800)-(0.600)]}, LSAP {-1.200[(-1.700)-(-0.200)] vs -1.300 [(-1.85)-(-0.400)]} were also similar in study and control groups. Presence of normal BMD (9/41 vs 8/41), osteopenia (16/41 vs 18/41) and osteoporosis (16/41 vs 15/41) were comparable between the study and control groups. No significant difference was observed in the BMD, T-scores and Z-scores at NOF and LSAP among T2DM patients treated with thiazolidinediones; those treated with other OHA and controls.Interpretation & conclusions:The present findings show that the use of OHA for a period of three years or more does not significantly affect the BMD in patients with T2DM.

Use of rosiglitazone and pioglitazone immediately after the cardiovascular risk warnings

Background Meta-analyses of oral hypoglycemic agents (OHAs) revealed that rosiglitazone increased the risk of myocardial infarction (MI) and heart failure (HF) and that pioglitazone increased the risk of HF and decreased the risk of MI. Objective To characterize the change in the pattern of use of OHAs immediately after the publication of these meta-analyses on May 21, 2007. Methods Pharmacy and medical claims data for a managed care organization were analyzed for patients continuously enrolled from January 1, 2005, to November 30, 2007, with at least 1 pharmacy claim for OHA in the 13-month period between November 1, 2006, and November 30, 2007. A 5-month pre-publication period (November 1, 2006, through March 31, 2007) was compared with a 5-month post-publication period (July 1, 2007, through November 30, 2007) using a differences-in-differences multinomial logistic regression. This regression explored discontinuation; continuation with monotherapy or adding another drug; and switching to a drug different from the index monotherapy drug after adjusting for gender, age, type of insurance, past 1-year history of MI or HF, and risk factors for MI and HF in the past 1 year. Results The relative rate of switching to nonindex drug in the postpublication relative to prepublication was 2.64 ( P = .046) for monotherapy rosiglitazone users and 0.72 ( P = .583) for monotherapy pioglitazone users. The differences-in-differences estimate of the rate of switching to nonindex drugs for monotherapy rosiglitazone users was 3.64 ( P = .090) times higher relative to the estimate for monotherapy pioglitazone users. Conclusion The pattern of use differed fundamentally between monotherapy rosiglitazone users and users of all other monotherapy OHAs in the postperiod. Not only were monotherapy rosiglitazone patients switching to non-rosiglitazone drugs at a higher rate, but the rate also was more than 3 times higher than similar switches among monotherapy pioglitazone users in the postperiod relative to the preperiod. This shows that the market response as observed by patient/prescriber decisions to the adverse news was interpreted narrowly to monotherapy rosiglitazone, and there is little or no spillover to the other drugs. Therefore, this study found that there was a differential effect of meta-analyses on the use of the 2 drugs.

A comparison on insulin regimen treatment of elderly (&gt;70 years) and younger (&lt;70 years) type 2 diabetic patients in actual clinical practice

The incidence of type 2 diabetes mellitus increases with age. However, there are few data about the most adequate type of insulin, or the most adequate insulin regimen, for elderly patients with diabetes. The present study compared insulin regimens in patients aged more than 70 years (100 subjects) with those aged less than 70 years (73 subjects) who attended a diabetes outpatient clinic. The weight, body mass index, diabetes-associated chronic complications, other cardiovascular risk factors, type of insulin, insulin regimen, total daily dose of insulin, weight-adjusted total daily dose of insulin, concomitant treatment with oral hypoglycaemic agents (OHA) and glycosylated haemoglobin (HbA1c) were compared between the two groups. Although both groups had the same level of metabolic control (HbA1c: 7.66 ± 0.91 in the elderly group vs. 7.62 ± 0.96 in the younger group), we have found that elderly subjects were more likely to be treated with a simple regimen, as shown by a higher use of basal insulin (15% in young patients and 41% in the elderly group; P < 0.001), lower use of fast-acting insulin (32.8% vs. 15%; P = 0.005), and fewer daily injections (45% vs. 22% received at least three injections each day; P = 0.001). There were no differences in the use of OHA; however, the majority of young patients were treated with metformin, whereas repaglinide was most commonly used in the elderly group. In conclusion, in everyday clinical practice, elderly subjects were treated with the simplest regimen and achieved the same level of metabolic control as young diabetic patients.

Oral hypoglycemic therapy: Understanding the mechanisms of transplacental transfer

The current trend towards an increase in the rate of Type 2 diabetes in women of childbearing age will inevitably result in an increasing number of women requiring hypoglycemic therapy throughout pregnancy. For patients with Type 2 diabetes or gestational diabetes, oral hypoglycemic agents (OHAs) represent an attractive alternative to insulin therapy. However, there exists some apprehension regarding the use of OHAs during pregnancy. Although the current accepted understanding is that most drugs administered during pregnancy can permeate the placental barrier, there is sufficient evidence to suggest that the placenta is capable of limiting fetal exposure to drugs. In particular, large sets of data on the transplacental transfer and clinical use of glyburide in pregnancy have suggested that glyburide may be a safe alternative to insulin therapy. Glyburide's limited fetal transfer has been attributed to its high protein binding, rapid clearance rate and the role of placental efflux transporters such as the breast cancer resistance protein. However, there are a number of maternal, placental and fetal factors that may alter the transplacental passage of drugs used in pregnancy. Therefore, it is essential that OHAs are further investigated to determine their safety with confidence and provide better treatment options for diabetes in pregnancy.