Use Of Sulfonylureas Research Articles

Anti-diabetic medications and the risk for colorectal cancer: A population-based nested case-control study

BackgroundTo evaluate whether anti-diabetic medications are related to colorectal cancer (CRC) risk in type 2 diabetes patients. MethodsThe study was performed from a population-based prospective cohort provided by the National Health Insurance Corporation (2007–2014). Among the 2,084,602 patients newly diagnosed as type 2 diabetes in this period, the cases had incident CRC identified at least 3 years after the diagnosis, and the controls were matched to each case by age, sex, body mass index (BMI), fasting plasma glucose level, and year of the diagnosis. Conditional logistic regression was used to calculate the adjusted odds ratio (aOR) and its 95 % confidence intervals (CIs) for CRC by anti-diabetic medications. ResultsA total of 4,228 cases were identified and 4,228 controls were matched to the cases. Sulfonylurea use increased the risk for CRC [aOR (95 % CI), 1.14 (1.05–1.25)], showing an increasing trend with increasing cumulative doses (p for trend = 0.0008). In subgroup analysis, sulfonylurea use increased the CRC risk in DM patients ≥ 65 years, but not in the patients < 65 years. Among sulfonylurea drugs, gliclazide decreased the CRC risk [0.85 (0.72–1.00), p < 0.05], whereas glimepiride increased the risk significantly [1.14 (1.06–1.22)]. In contrast, metformin, meglitide, thiazolidinedione, dipeptidyl peptidase-4 inhibitors, and α-glucosidase inhibitor use did not modify the CRC risk. ConclusionsOur results suggest that sulfonylureas except for gliclazide increase the CRC risk in type 2 diabetic patients. Long-term follow-up studies are necessary to clarify the association of newer anti-diabetic medications with the CRC incidence.

Antidiabetic drug use trends in patients with type 2 diabetes mellitus and chronic kidney disease: A cross-sectional analysis of the National Health and Nutrition Examination Survey.

There is little information on medication use, trends across time, and the impact of guidelines on appropriate use of antidiabetic drugs in participants with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). A cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) from 2005-2016 was carried out for participants with T2DM with and without CKD. Multivariate survey-weighted regression models were used to evaluate trends in antidiabetic drug use across the time periods and CKD severity. Guideline-discordant use of metformin and glyburide were assessed among those with glomerular filtration rate and serum creatinine-based contraindications. Out of 3237 study participants with T2DM, 35.9% had CKD. Comparing 2013-2016 with 2005-2008, use of metformin (non-CKD: 69% vs 83.8%, CKD: 58.6% vs 68.2%) increased, whereas the use of sulfonylureas (non-CKD: 46.3% vs 27.2%, CKD: 54.7% vs 36.6%) and thiazolidinediones (non-CKD: 29.3% vs 3.9%, CKD: 24.6% vs 5.5%) decreased. In combined NHANES cycles and across stages of CKD severity, metformin use decreased (non-CKD, stage 1/2, stage 3, stage 4/5: 78.4%, 69.5%, 54.6%, 4.9%, respectively; P < .01), and insulin use increased (18.5%, 26.8%, 25%, 52.8%, respectively; P < .01) from non-CKD to progressed CKD. Guideline-discordant use of metformin and glyburide was observed in 8.3% and 2.8% of the participants, respectively, in 2013-2016. Use of particular antidiabetic medications in patients with CKD changed noticeably over the years, most in accordance with guidelines and regulatory decisions. Gaps in quality of care still exist, which warrants increasing awareness and implementing programs to mitigate inappropriate use.

UTILIZATION TRENDS OF NEWLY APPROVED GLUCOSE-LOWERING DRUGS FOR TYPE 2 DIABETES

Using Medicare fee-for-service data from 2013-2015, we identified 3.2 million patients per year (mean [SD] age, 74.7 years [standard deviation, 7.2]) who were treated with glucose-lowering drugs for type 2 diabetes. Between 2013 and 2015, the proportion of patients treated with sulfonylureas declined from 27.4% to 25.1%; those using DPP4is (11.5% to 12.0%) and GLP1-RAs (1.8% to 2.4%) remained unchanged; those using SGLT2is increased from 0.2% to 1.9%. In the subgroup of patients initiating a glucose-lowering drug without prior use of the same class agent, the proportion of patients starting sulfonylureas (18.7% to 17.2% of initiators), DPP4is (16.0% to 15.0% of initiators), and GLP1-RAs (3.4% to 4.2% of initiators) changed little between 2013 and 2015, while those starting SGLT2is increased from 0.7% to 6.5% of initiators. In the Medicare population, we observed a persistently high use of sulfonylureas and a rapid uptake of SGLT2is among the newer classes.

Heart failure in patients with diabetes in Campania

Heart Failure (HF) and Type 2 Diabetes Mellitus (T2D) are important clinical conditions that often coexist, mutually influencing intra- and extra-hospital morbidity and mortality. In order to characterize the diagnostic and therapeutic management of patients with HF and T2D, a retrospective observational study was conducted on database of the last 12 months in 8 Campania Diabetology Centers. 164 patients were affected by HF and T2D. Among them, 123 patients had a medical record with reproducible data and were recruited for the study. Diabetic patients were divided into three groups: group A included patients with preserved ejection fraction (EF) (&gt; 50 %), group B patients with midrange EF (40-49%) and the group C patients with reduced EF (&lt; 40%). All patients had performed ECG and echocardiography, repeated every 6 months; 41 patients (33% of the sample) also performed a cardiac Holter. The most frequent causes of HF were ischemic heart disease and hypertension. After a 12 months follow up, the clinical and laboratory parameters and the treatments adopted were re-evaluated. The antidiabetic drugs resulted modified with a reduction in the use of metformin, sulfonylureas, glinids and pioglitazone; at the same time a greater use of gliptins, gliflozines and GLP1 AR and a lower use of insulin therapy was observed. Cardiological therapy was modified with a greater use of diuretics and nitrates and a reduction of ACEI and ARB, probably due to the use of sacubitril/valsartan association in the group of patients with reduced EF. According to the recent guidelines, antidiabetic therapy must be tailored to the characteristics of the patients with diabetes and heart failure, preferring the use of molecules that have shown a cardiovascular protection effect or, secondarily, those with cardiovascular neutrality. Similarly, cardiological therapies have to consider the type of antidiabetic agents used and benefit from molecules that impact clinical symptoms and natural history. Finally, the approach to the patients with both the pathologies must necessarily take place in the healthcare districts and absolutely be multidisciplinary and integrated, involving firstly Diabetologists and Cardiologists, but also other professional roles (nurses, psychologists, physiotherapists, caregivers) operating in the territorial healthcare services. KEY WORDS diabetes mellitus; heart failure; ejection fraction.

Colorectal Cancer Risks According to Sex Differences in Patients With Type II Diabetes Mellitus: A Korean Nationwide Population-Based Cohort Study.

INTRODUCTION:Developing colorectal cancer (CRC) poses challenges for patients with type II diabetes mellitus (T2DM). We investigated CRC risk factors in patients with T2DM.METHODS:We retrospectively collected data from the National Health Insurance Corporation database, comprising approximately 97% of the Korean population. T2DM and CRC were defined according to International Classification of Disease codes (10th Revision) and claims data. Obesity was defined using body mass index (BMI); abdominal obesity was defined according to waist circumference. Other variables were defined using demographic, anthropometric, and laboratory data.RESULTS:Overall, 2,591,149 patients with T2DM were analyzed. During the follow-up period (median, 5.4 years), 24,236 CRC cases were identified. Aging (≥70 years), male sex, smoking, alcohol consumption, hypertension, and insulin and/or sulfonylurea use were significant risk factors for CRC. In males, smoking and alcohol consumption were more likely to lead to CRC, whereas a BMI increase was a more significant risk factor in females. Females with a BMI ≥ 25 kg/m2 and abdominal obesity were associated with an 18% increased risk of CRC compared with patients with normal weight and normal waist circumference (hazard ratio = 1.184, 95% confidence interval 1.123–1.25), whereas male patients with a BMI ≥ 25 kg/m2 and abdominal obesity were associated with an 8% increased risk (hazard ratio = 1.087, 95% confidence interval 1.049–1.127).DISCUSSION:Patients had CRC risk factors that differed according to sex. Smoking and heavy alcohol consumption were risks of CRC in males. Female patients with a BMI ≥ 25 kg/m2 and abdominal obesity were at a higher risk of developing CRC than males.

Association of Treatment With Metformin vs Sulfonylurea With Major Adverse Cardiovascular Events Among Patients With Diabetes and Reduced Kidney Function

Before 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown. To compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea. Retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016). New users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function. MACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death. There were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use. Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.

National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015.

ObjectiveDespite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years.Research design and methodsThis cross-sectional study utilized data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%.ResultsA total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55–73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%).ConclusionsNational ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing.

Metformin and Sulfonylurea Use and Risk of Incident Dementia

ObjectiveTo compare incident dementia risk among patients who initiated treatment with metformin or sulfonylurea in Veterans Health Affairs (VHA) patients with replication in Kaiser Permanente Washington (KPW) patients to determine whether first-choice antidiabetic medications are associated with reduced risk of dementia. Patients and MethodsCohorts contained 75,187 VHA patients and 10,866 KPW patients, 50 years and older, who initiated monotherapy with metformin or sulfonylurea. Patients were free of dementia diagnoses and any diabetes treatment for 2 years before cohort entry. Variables were extracted from electronic health data from VHA (1999-2015) and KPW (1996-2015), which included diagnosis codes, pharmacy data, laboratory values, and demographic characteristics. Propensity scores and inverse probability of treatment weighting controlled for confounding. ResultsVeterans Health Affairs patients were 60.8±6.8 years of age on average, and KPW patients were 63.1±9.5 years of age. In the VHA sample, 72,769 (96.8%) were male; and in the KPW sample, 5480 (50.4%). After adjusting for confounding, metformin initiation was associated with a significantly (P=.02) lower risk of dementia in VHA (hazard ratio, 0.9; 95% CI, 0.9-1.0), with a similar point estimate in KPW (hazard ratio, 0.9; 95% CI, 0.7-1.1). Metformin was not associated with dementia risk in patients 75 years and older. ConclusionExisting epidemiological studies of metformin and incident dementia have been inconsistent. Using a similar study design in 2 patient populations that differed in clinical and demographic characteristics, our results provide robust evidence that metformin use is associated with a modestly lower risk of incident dementia.

Monogenic diabetes in children

Monogenic forms of diabetes account for approximately 1–2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported. Children with antibody-negative, C-peptide-positive diabetes should be evaluated and genetically tested for monogenic diabetes. Accurate genetic diagnosis impacts treatment in the most common types of monogenic diabetes, including the use of sulfonylureas in place of insulin or other glucose-lowering agents or discontinuing pharmacologic treatment altogether.

Association Between Metformin Initiation and Incident Dementia Among African American and White Veterans Health Administration Patients.

African American patients are more likely to experience cognitive decline after type 2 diabetes mellitus onset than white patients. Metformin use has been associated with a lower risk of dementia compared with sulfonylureas. Evidence for whether this association differs by race is sparse. Veterans Health Administration (VHA) medical record data were obtained for 73,761 African American and white patients aged ≥50 years who used the VHA from fiscal years 2000 to 2015. Patients were free of dementia and diabetes medications during fiscal years 2000 and 2001 and subsequently initiated metformin or sulfonylurea monotherapy. For race and age subgroups, Cox proportional hazards models using propensity scores and inverse probability of treatment weighting to control for confounding were computed to measure the association between metformin vs sulfonylurea initiation and incident dementia. After controlling for confounding, among patients aged ≥50 years, metformin vs sulfonylurea use was associated with a significantly lower risk of dementia in African American patients (hazard ratio [HR] = 0.73; 95% CI, 0.6-0.89) but not white patients (HR = 0.96; 95% CI, 0.9-1.03). The strongest magnitude of association between metformin and dementia was observed among African American patients aged 50 to 64 years (HR = 0.6; 95% CI, 0.45-0.81). Among those aged 65 to 74 years, metformin was significantly associated with lower risk of dementia in both races. Metformin was not associated with dementia in patients aged ≥75 years. Metformin vs sulfonylurea initiation was associated with a substantially lower risk of dementia among younger African American patients. These results may point to a novel approach for reducing the risk of dementia in African Americans with type 2 diabetes mellitus.

Precision Medicine: Long-Term Treatment with Sulfonylureas in Patients with Neonatal Diabetes Due to KCNJ11 Mutations.

The goal of this review is to provide updates on the safety and efficacy of long-term sulfonylurea use in patients with KCNJ11-related diabetes. Publications from 2004 to the present were reviewed with an emphasis on literature since 2014. Sulfonylureas, often taken at high doses, have now been utilized effectively in KCNJ11 patients for over 10years. Mild-moderate hypoglycemia can occur, but in two studies with a combined 975 patient-years on sulfonylureas, no severe hypoglycemic events were reported. Improvements in neurodevelopment and motor function after transition to sulfonylureas continue to be described. Sulfonylureas continue to be an effective, sustainable, and safe treatment for KCNJ11-related diabetes. Ongoing follow-up of patients in research registries will allow for deeper understanding of the facilitators and barriers to long-term sustainability. Further understanding of the effect of sulfonylurea on long-term neurodevelopmental outcomes, and the potential for adjunctive therapies, is needed.

Incident Hepatocellular Carcinoma Risk in Patients Treated with a Sulfonylurea: A Nationwide, Nested, Case-Control Study

Several studies have shown that the use of sulfonylureas in patients with type 2 diabetes mellitus (T2DM) is associated with a higher risk of hepatocellular carcinoma (HCC). In this study, we investigated the effects of individual sulfonylureas on HCC development using the National Health Insurance Service-National Sample Cohort in South Korea. Among 47,738 subjects aged 40 years or older who had newly diagnosed with diabetes, 241 incident HCC cases and 1205 matched controls were identified. Adjusted odds ratios (ORs) as estimates of the relative risk of HCC were calculated using logistic regression analysis. Compared to patients never treated with a sulfonylurea, those treated with a sulfonylurea had a 1.7-fold increased risk of HCC development. Of the different types of sulfonylureas, the exclusive use of glimepiride was associated with a significantly elevated risk of HCC (OR = 1.89, 95% CI = 1.02–3.47) compared to those who were never treated with sulfonylureas. No significant associations were observed between exclusive gliclazide use and incident HCC (OR = 2.04, 95% CI = 0.75–5.52). In conclusion, the association between the use of sulfonylureas and risk of HCC was different according to the type of sulfonylurea, in patients with new-onset T2DM. Further prospective studies are warranted to confirm these results and translate them into clinical practice.

1248-P: Estimating Diabetes Duration from Electronic Medical Records (EMRs) with an Intrinsic Diabetes Risk Prediction Model: From Clinical Trial to Real-World Clinical Practice

We have previously described the utility and high predictive value of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) model, which was developed from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial data. However, it uses diabetes duration as a key factor for modelling diabetes progression, and diabetes duration is not routinely collected in EMRs. This study use machine learning to estimate diabetes duration with EMR information. Among individuals (N=8,026) with complete records from the ACCORD trial, diabetes duration was estimated with an ordinary least squares (OLS) model, a least absolute shrinkage and selection operator (LASSO) model, a pruned decision tree model, and a random forest model using 37 baseline predictors such as biomarkers, demographics, disease history, and medications. Model performance was compared using root-mean-square Error (RMSE), mean-absolute error (MAS), and R-squared. All three indicators were calculated through 10-fold cross-validation with 1000 iterations in order to address over-fitting. Age, current HbA1c value, retinopathy, number of oral antidiabetic drugs, number of Insulin types, and use of sulfonylureas were identified as key predictors for patient-reported diabetes duration. The random forest model achieved the best performance on all three indicators (RMSE=6.16, MAE= 4.71, R2=0.30), significantly higher than the pruned decision tree model (RMSE=6.57, MAE= 5.03, R2=0.21) and LASSO model (RMSE=6.60, MAE= 5.08, R2=0.20). Diabetes duration can be predicted using fields routinely included in EMRs. Integration of the results of this prediction equation into predictive diabetes models (such as BRAVO) will allow patient-specific estimates of diabetes duration based solely on EMRs. This will increase precision when inferring risk level and using models to aid clinical decision making among patients with type 2 diabetes. Disclosure H. Shao: None. S. Yang: None. C. Stoecker: None. V. Fonseca: Board Member; Self; American Association of Clinical Endocrinologists. Consultant; Self; Abbott, Asahi Kasei Corporation, Novo Nordisk Inc., Sanofi US, Takeda Pharmaceutical Company Limited. Research Support; Self; Bayer US. Stock/Shareholder; Self; Amgen Inc., BRAVO4HEALTH, Mellitus Health. X. Cheng: None. L. Shi: None.

670-P: Provider Medication Use Changes for Better and Worse with Education

ADA guidelines for type 2 diabetes recommend metformin (MET) at all A1c levels, combination (COMBO) therapy at higher A1c levels and insulin (INS) for symptoms or A1c &amp;gt; 10. Current provider adherence to guidelines and the ability of educational session to alter that are unclear. Methods: We assessed provider medication use before and after didactic diabetes medication and case management sessions designed to encourage multi-combination therapy and guideline adherence. Surveys asked 163 participants to report preferred drug regimens to be used for 6 patient cases: newly diagnosed (NEW) or established (EST) diabetes patients with A1c of 7.5 (LO), 9.5 (MID) or 10.5 (HI). Results: MET use was remarkably low at higher A1c’s (69% HI, 85% MID, 98% LO) at baseline. After sessions, MET use improved significantly to 84%, 94%, 99%. COMBO (no-INS) was most frequently chosen for MID A1c levels: NEW 67%/EST 43%; compared to 13%/23% for LO 7%/5% HI. In the higher A1c cases, COMBO use increased dramatically with sessions to: 83%/72% MID, 30%/16% HI (all p&amp;lt; 0.005). Use of sulfonylureas decreased for 5 of the 6 cases. Changes in INS use were nuanced. Few providers (2%/4%) chose insulin for LO A1c; this decreased to near 0 after the sessions. INS was used in the majority of patients with HI A1c. INS use decreased significantly in favor of COMBO, not only for MID A1c (38%/51% to 13%/26%), but also for HI (93%/94% to 70%/84%). Summary: Initially, guideline adherence was sub-optimal (underutilization of MET, COMBO and at HI A1c of INS). Short Provider Education sessions improved practices. Use of COMBO’s less likely to cause hypoglycemia increased substantially. However, appropriate INS at HI A1c also decreased. Conclusion: There is a need for more training for better use of the antidiabetic armamentarium by primary care providers. Provider education emphasizing COMBO advantages improves planned prescribing patterns, but careful message tailoring is needed to avoid unintended consequences. Disclosure S. Sarkar: None. C.S. Barnes: None. J. Caudle: None. S.M. John: None. K.P. Clark: None. E. Heiman: None. J.C. Volcy: None. S. Schmidt: None. D.C. Ziemer: None. Funding Sanofi U.S.

A Study of Kir6.2 Gene Sequence in Rat Model of Type 2 Diabetes Mellitus Treated by CSN1S2 Protein of Etawah Crossbred Goat Milk

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia. High blood glucose levels in T2DM patients are treated by sulfonylurea. However, the long-term use of sulfonylurea can affect the regulation of glucose homeostasis and cause hypoglycemia. The cascade gene associated with the hypoglycemia is Kir6.2, a constituent of ATP-sensitive potassium channel (KATP), in the neuron. Kir6.2 mutations cause dysregulation of insulin secretion by pancreatic beta cells and glucagon secretion by pancreatic alpha cells. The aim of this study was to analyze the effect of CSN1S2 protein of etawah crossbred goat milk on Kir6.2 gene sequences in the rat model of T2DM. The experimental animals used were male Wistar rats (Rattus norvegicus) which were divided into two major groups, namely control group and T2DM group. Each group was administrated by CSN1S2 protein with the dose of 375 mg/kg BW, 750 mg/kg BW, 1500 mg/kg BW, and without CSN1S2 protein administration. Each group was replicated three times. DNA was isolated from the rat brain. Kir6.2 gene was amplified by using specific primers. PCR products were purified and sequenced by using ABI 3730xl DNA Sequencer. DNA sequences were analyzed by using MEGA7 software. Amplification of the Kir6.2 gene produced 1173 bp DNA. There was no change in the Kir6.2 sequence in all treatments. The 25 mg/kg BW dose of streptozotocin had no effect on Kir6.2 gene sequence in the rat brain. This study also showed that administration of CSN1S2 protein at the dose of 375 mg/kg BB, 750 mg/kg BW, and 1500 mg/kg BW did not cause mutations in the Kir6.2 gene in the brain of the rat model of T2DM.

929-P: Clinical Factors Associated with the Glucagon Stimulation Test and Daily and Day-to-Day Glucose Variability Determined by Continuous Glucose Monitoring in Type 2 Diabetic Patients

Aims: We studied clinical factors in association with the glucagon stimulation test and daily and day-to-day glucose variability as determined by continuous glucose monitoring (CGM). Methods: We performed a cross-sectional analysis of type 2 diabetes (T2DM; insulin-treated, n=83; not insulin-treated, n=126) patients who underwent the glucagon stimulation test and over 72 h of continuous glucose monitoring. Correlations of clinical factors with the mean amplitude of glycemic excursions (MAGE), percentage coefficient of variation for glucose (%CV), and mean of daily differences (MODD) in CGM were analyzed. Results: In T2DM with insulin therapy, age and HbA1c were correlated with MAGE and %CV; FPG was correlated with MAGE and MODD; and the increment of CPR (ΔCPR) was inversely correlated with MAGE, %CV, and MODD. In T2DM without insulin therapy, age, diastolic blood pressure, and triglycerides were correlated with MODD; ΔCPR was inversely correlated with %CV; HbA1c was correlated with MAGE and MODD; the use of α-glucosidase inhibitors was inversely correlated with %CV; and the use of sulfonylurea (SU) was correlated with MAGE and %CV. Conclusions: Insulin secretion is related to glucose variability in insulin-treated T2DM. Poor glycemic control greatly contributes to glucose variability in T2DM. SU administration increases the daily glucose variability in T2DM without insulin therapy. Disclosure M. Ohara: None. H. Nagaike: None. S. Goto: Research Support; Spouse/Partner; DENKA SEIKEN CO., LTD. H. Kushima: None. M. Hiromura: None. T. Yamamoto: None. Y. Mori: None. T. Fukui: None. T. Hirano: None.

1554-P: Real-Word Use of Insulin and Oral Antidiabetes Drugs in the Hospital

Insulin therapy is the preferred treatment for glycemic control in the hospital. Oral antidiabetes drugs (OAD) are commonly used despite the lack of safety and efficacy data. We analyzed individual patient-data of non-critically ill patients with T2D admitted to a teaching medical institution between 2008 - 2018 to determine the relative efficacy and safety of OAD. We did logistic regression analysis adjusting for relevant covariates. A total of 10,205 patients were included in the analysis, 970 patients (9.5%) were treated with OAD, 691 (6.8%) with OAD plus basal insulin, and 8,544 (83.7%) with basal insulin. Patients treated with OAD had lower admission BG and HbA1c and had less comorbidities compared to those receiving basal insulin. Hypoglycemia was less common with metformin (2.4%) and DPP-4i (0.0%) compared to sulfonylureas (13%) or insulin therapy (13%). After adjusting for age, gender, BMI, race, hospital setting, Charlson score, and admission creatinine, treatment with OADs was associated with better BG control and lower odds of complications compared to insulin use (Figure). Conclusion: The use of OAD in the hospital appears to be safe and effective and is not associated with higher odds of complications, with the exception of sulfonylurea use that is associated with a high rate of hypoglycemia. Residual confounding due to selection assignment to basal insulin therapy to sicker patients is probable. Disclosure F.J. Pasquel: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. M.F. Magee: Consultant; Self; Mytonomy. Research Support; Self; Lilly Diabetes, Mytonomy, Sanofi. Speaker's Bureau; Self; PRIMED. I. Hochberg: None. R.B. Hawthorne: None. L. Peng: None. G.E. Umpierrez: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc. Research Support; Self; AstraZeneca, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US.

133-LB: High Hypoglycemia Risk Patients with T2D on First-Generation Basal Insulins (BI) in the U.S. Have a Lower Risk of Hypoglycemia after One Year following Switch to Insulin Glargine 300 U/mL (Gla-300) vs. First-Generation BIs (DELIVER - High Risk)

DELIVER - High Risk study compared long-term clinical outcomes for patients with T2D and high hypoglycemia risk on first-generation BIs who were switched to Gla-300 or other first-generation BIs (other switchers). Electronic medical record data from the PHIE database were used. Eligible patients (age &amp;gt;18 years) had ≥1 criterion for high hypoglycemia risk (age &amp;gt;64 years; basal-bolus insulin use; renal impairment; uncontrolled baseline A1C; sulfonylurea use; atherosclerotic cardiovascular disease; history indicating high risk, including ≥1 severe hypoglycemic episode (prior 12 months). Endpoints were A1C reduction from baseline to 9-12 months, attainment of A1C goals (&amp;lt;7.0%; &amp;lt;8.0%), and hypoglycemia (based on ICD-9-CM codes or blood glucose ≤70 mg/dL) at 12 months. In a propensity score-matched comparison of Gla-300 vs. other switchers (Table), mean A1C reduction from baseline and attainment of A1C goals were comparable. Significantly fewer Gla-300 vs. other switchers experienced inpatient/ED-related hypoglycemia. For T2D patients at high hypoglycemia risk in a real-world setting, Gla-300 was associated with a significantly lower risk of hypoglycemia than switching to other BIs, 1 year after switching, while delivering similar glycemic control. Disclosure S.D. Sullivan: Research Support; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Sanofi. A.A. Menon: None. R. Gupta: None. J. Wu: Employee; Self; Sanofi US. C. Nicholls: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. Funding Sanofi

1503-P: Seasonal Changes in the Achievement of Guideline Goals for HbA1c, Blood Pressure, and Cholesterol in Patients with Type 2 Diabetes Mellitus: A Nationwide Population-Based Study (ABC Study)

Aim: Precise monthly achievement rates for reaching guideline goals for HbA1c, blood pressure (BP), and cholesterol levels remain unknown. We evaluated achievement rates on a monthly basis in patients with type 2 diabetes mellitus (T2DM) and explored related factors. Material and Methods: This retrospective study initially analyzed data on 104,601 patients with T2DM throughout Japan (38 medical clinics). Patients whose HbA1c, BP, and low-density lipoprotein (LDL)-cholesterol were measured ≥12 times during a 2-year period were included. We evaluated monthly achievement rates. Achieved goals were defined as HbA1c &amp;lt;7%, BP &amp;lt;130/80 mmHg, and LDL-cholesterol &amp;lt;100 mg/dL. Achievement of all goals was expressed as the "all ABC achievement." Results: A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA1c, BP, and LDL-cholesterol exhibited seasonal variations with the lowest rates in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA1c, 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL-cholesterol, 50.8%, 47.2%). In the multiple logistic regression analysis, in winter, BMI ≥25 kg/m2 (BMI 25-30 kg/m2, odds ratio 0.45 [0.29-0.70], p &amp;lt; 0.001; BMI ≥30 kg/m2, 0.35 [0.22-0.57], p &amp;lt; 0.001) and diabetes duration ≥10 years (0.53 [0.37-0.76], p &amp;lt; 0.001) were independently related to lower achievement rates for HbA1c, and age ≥65 years (0.47 [95% CI 0.34-0.63], p &amp;lt; 0.001) was independently related to decreased achievement rates for SBP. Insulin and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter. Conclusion: This study showed that in patients with T2DM, the achievement rates for blood glucose, BP, and lipid goal levels varied seasonally. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices. Disclosure D. Matsutani: None. M. Sakamoto: None. S. Minato: None. Y. Tsujimoto: None. Y. Kayama: None. K. Utsunomiya: None. M. Nishikawa: None.

9-LB: Hypoglycemia in Patients with Diabetes: Therapeutic Strategies and Associated Risk Factors

Use of insulin or sulfonylureas (SU) carries a risk of hypoglycemia, but the risk with different diabetes therapies, such as premixed insulin, is not well known. We conducted a case-control analysis of 297,263 patients with DIAB and 487,226 NONDIAB in the national VA database who had ≥4 primary care visits, ≥1 A1c, and ≥3 outpatient random plasma glucoses (RPG) in 2002-2003, and examined hypoglycemia by diabetic medication use and other risk factors, through 2012. Hypoglycemia was defined as severe (Emergency Department visit with hypoglycemia [EDHypo]) and by outpatient lab (RPGHypo = RPG &amp;lt;70 mg/dl); both were associated with increased mortality (2.1- and 1.5-fold, respectively, p&amp;lt;0.001). At baseline, DIAB had mean age 66 year, BMI 31 kg/m2, and A1c 7.5%; and were 98% male, 80% white, and 18% with retinopathy; NONDIAB were similar but had lower BMI. Among DIAB, 49% were on SU, 29% insulin (5% basal, 5% basal+SU, 1% bolus, 8% basal+bolus, 10% premixed), 11% otherRx (non-insulin/non-SU), 11% no meds. RPGHypo and EDHypo occurred in 6.8% and 0.3% of DIAB, respectively, vs. 2.1% and &amp;lt;0.1% of NONDIAB, p&amp;lt;0.001. During mean follow-up 7.5 year, 35% of DIAB (n=102,063; 229,612 events) had ≥1 RPGHypo, an incidence rate of 0.10 events/pt-year, and 4% had EDHypo. In adjusted models compared to otherRx, the risk of any hypo and EDHypo, respectively, was highest with basal+bolus (OR 1.4 and 17.8) and premixed insulin (OR 1.4 and 13.8), and lower with basal Insulin (OR 1.4 and 10.5), and SU (OR 1.2 and 5.1), all p&amp;lt;0.001. Black race and retinopathy also conferred higher risk of both any hypoglycemia and EDHypo (black race, OR 1.9 and 2.1; retinopathy OR 1.3 and 1.6, respectively; all p&amp;lt;0.001), much higher than the risk with A1c &amp;lt;6.0% (OR 1.0 and 1.3). Conclusions: Clinically significant hypoglycemia, including both outpatient RPG &amp;lt;70 mg/dl and ED visits, is common in DIAB patients, particularly in those using basal+bolus or premixed insulin, and with black race or retinopathy, and should prompt consideration of altered management. Disclosure S.C. Markley Webster: Stock/Shareholder; Self; Dexcom, Inc. K.E. Kurgansky: None. L.S. Phillips: Advisory Panel; Self; Janssen Pharmaceuticals, Inc. Research Support; Self; AbbVie Inc., GlaxoSmithKline plc., Kowa Pharmaceutical Europe Co. Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Pfizer Inc. Stock/Shareholder; Self; Diasyst Inc. Other Relationship; Self; Diasyst Inc., Janssen Pharmaceuticals, Inc. D.R. Gagnon: None. P.W. Wilson: None. M.K. Rhee: None. Funding Million Veteran Program