Metformin Prescription Research Articles

960-P: Characteristics of U.S. Patients with Type 2 Diabetes Prescribed GLP-1RA+SGLT2i in Combination during 2018

Randomized controlled trials (RCTs) support use of a glucagon-like peptide-1 receptor agonist (GLP-1RA) combined with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) in people with type 2 diabetes (T2D). As RCTs do not fully reflect the real world, there is a need to explore the real-world population on this combination and determine outcomes with this approach. As a first step, in this large-scale cross-sectional study, we identified adults with T2D, ≥2 prescriptions for GLP-1RA and/or SGLT2i and available data from electronic medical records in the U.S. IBM Explorys database. The first prescription of GLP-1RA and/or SGLT2i in 2018 set the index date, irrespective of prior prescriptions. Data 6 months pre-index were used for patient characteristics and up to 5 years pre-index for medical history. Of 41,421 patients, 12.8% had GLP-1RA+SGLT2i prescribed together, 46.0% GLP-1RA and 41.2% SGLT2i. Of those prescribed both drugs, female: 48.0%; BMI ≥35 kg/m2: 50.2%; mean age: 56.2 years; mean HbA1c 8.3%. In multinomial regression, there was little difference between those prescribed GLP-1RA+SGLT2i vs. either drug alone in terms of HbA1c or presence of comorbidities (data not shown). However, those prescribed both drugs vs. GLP-1RA alone were less likely to be ≥65 years (odds ratio 0.57 [95% CI 0.51;0.63]), have a history of chronic kidney disease (CKD; 0.56 [0.49;0.66]) and more likely to have prior prescription of metformin (1.56 [1.46;1.68]). Those prescribed both drugs vs. SGLT2i alone were less likely to be ≥65 years (0.60 [0.54;0.67]) and have prior prescription of dipeptidyl peptidase-4 inhibitor (0.57 [0.52;0.61]), but more likely to have BMI ≥35 kg/m2 (2.11 [1.75;2.54]) and prior prescription of insulin (1.97 [1.84;2.11]). Those prescribed GLP-1RA+SGLT2i vs. either drug in 2018 had many common characteristics. However, key differentiators (age, obesity, CKD history and prior glucose-lowering drugs) reflected considerations for each therapy based on data available then. Disclosure R.J. McCrimmon: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis. H.N. Christensen: Employee; Self; AstraZeneca, Novo Nordisk A/S. I. Holst: Employee; Self; Novo Nordisk A/S. A. Lenart: Employee; Self; Novo Nordisk A/S. B. Ludvik: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Speaker’s Bureau; Self; Amgen. R.S. Brandt: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J.S. Piltoft: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. A. Philis-Tsimikas: Advisory Panel; Self; Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

2283-PUB: Metformin Treatment and Prostate Cancer Risk: Cox Regression Analysis with Time-Dependent Covariates of 150,000 Men with Incident Diabetes Mellitus

Background: There is conflicting evidence regarding the association between metformin use and prostate cancer risk in diabetic men. Objective: We investigated the association of metformin treatment, as a time dependent exposure, with prostate cancer incidence, in a population-based cohort of T2D incident men, while accounting for major time related biases, time-dependent confounding by glucose levels, and for use of other diabetes medications. Methods: During 2002-2012, we followed a cohort of 145,617 incident diabetic men aged 21-87 years insured in the largest health maintenance organization in Israel. We used a discrete form of the weighted cumulative exposure to metformin to evaluate its association with prostate cancer incidence. This was implemented in a time-dependent covariate Cox model, adjusting for age, ethnic background, and socioeconomic status. Other diabetes medications were not found to be strongly associated with prostate cancer. To account for time- dependent confounding by glucose levels, we used Propensity Score weighting for receiving metformin at each time-point. Results: There were 1,592 prostate cancer events occurring over a total of 910,000 person-years. We found a positive association of prostate cancer with metformin exposure in the previous year (hazard ratio (HR) for 1 defined daily dose = 1.66; 95%CI 1.23, 2.24), but a negative association with metformin exposure in the previous 2-7 years (HR=0.57; 95%CI 0.32, 1.02). Conclusion: Our results do not support a clear causal effect of metformin treatment on the incidence of prostate cancer. The positive association with metformin given in the previous year could be due to reverse causation of the cancer raising glucose levels and causing increased prescription of metformin. The negative association with metformin given 2-7 years previously is of borderline statistical significance and requires further research. Disclosure R. Dankner: None. H. Murad: None. N. Agay: None. L. Olmer: None. L.S. Freedman: None.

MON-601 Obesity Pharmacotherapy Is Effective in the United States Veterans Affairs Patient Population: A Local and Virtual Cohort Study

Background: Overweight and obesity are major health burdens, and the military veteran population may be disproportionately affected. Multiple new pharmacologic agents and combinations have been approved by the FDA for use in medical weight management. Using deidentified records from our local interdisciplinary weight management clinic and a national clinical data repository, we assessed obesity pharmacotherapy use and its real-world effectiveness for weight loss and improvement of comorbid metabolic parameters in this vulnerable population. Methods: During the initial year of the local weight management clinic, we found over 50 records with monthly followup of lifestyle intervention augmented by obesity pharmacotherapy. In the national clinical data repository, we identified over 2 million records for unique individuals prescribed bupropion-naltrexone, liraglutide, lorcaserin, orlistat, or phentermine-topiramate, and metformin considered as a control prescription. We selected records with detailed documentation of weight trends from 1 year before to 1 year after first prescription date for further analysis. Results: The most commonly prescribed medications in our local weight management clinic were metformin, liraglutide, orlistat, and combination phentermine/topiramate. On average, we observed −4.0 ± 2.1 kg weight loss over the initial 6-month intervention in records that completed at least 3 visits within this period. In the national database, over 800,000 records for an obesity or control metformin prescription provided adequate weight documentation to compare weight slopes during the year before and after the prescription start date. Records for metformin prescriptions showed −0.04 ± 0.008 kg/week difference in weight slope over one year before versus after the prescription start date. The greatest difference in weight slope was seen with phentermine-topiramate (−0.13 ± 0.03 kg/week), followed by lorcaserin, liraglutide, bupropion-naltrexone, and orlistat. Conclusions: Our data suggests that veterans with obesity experience weight loss at 1 year follow-up when engaged with our interdisciplinary weight management clinic. Nationally, veterans with obesity experience modest weight loss when prescribed pharmacotherapy. Taken together, our two data sources provide complementary perspectives to help guide obesity pharmacotherapy in veterans with obesity.

Metformin Treatment Is Associated with a Decreased Risk of Nonproliferative Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study.

Purpose To assess the relationship between metformin use and the severity of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) and to investigate the effect of metformin dosage on reducing the incidence of DR. Methods The study population included patients with newly diagnosed T2DM, who were aged ≥20 years and prescribed with antidiabetic drug therapy lasting ≥90 days, as identified using the National Health Insurance Research Database between 2000 and 2012. We matched metformin users and nonusers by a propensity score. Cox proportional hazard regression analyses were used to compute and compare the risk of developing nonproliferative diabetic retinopathy (NPDR) in metformin users and nonusers. Results Overall, 10,044 T2DM patients were enrolled. Metformin treatment was associated with a lower risk of NPDR (aHR 0.76, 95% CI 0.68–0.87) and sight-threatening diabetic retinopathy (STDR, aHR 0.29, 95% CI 0.19–0.45); however, the reduction in risk was borderline significant for STDR progression among NPDR patients (aHR 0.54, 95% CI 0.28–1.01). Combination therapy of metformin and DPP-4i exhibited a stronger but inverse relationship with NPDR development (aHR 0.32, 95% CI 0.25–0.41), especially at early (<3 months) stages of metformin prescription. These inverse relationships were also evident at different metformin doses and in adapted Diabetes Complications Severity Index scores (aDCSI). Moreover, combination therapy of metformin with sulfonylureas was associated with an increased risk of NPDR. Conclusion Metformin treatment in patients with T2DM was associated with a reduced risk of NPDR, and a potential trend was found for a reduced STDR risk in patients who had previously been diagnosed with NPDR. Combining metformin with DPP-4i seemingly had a significantly beneficial effect against NPDR risk, particularly when aDCSI scores were low, and when metformin was prescribed early after T2DM diagnosis. These results may recommend metformin for early treatment of T2DM.

Metformin adherence and discontinuation among patients with type 2 diabetes: A retrospective cohort study

AimsTo describe discontinuation and adherence to metformin in the United Kingdom. MethodsThis was a retrospective analysis of data from the Clinical Practice Research Datalink database of type 2 diabetes patients aged ≥18 years with ≥1 metformin prescription in 2013. Metformin use was assessed in new and ongoing users, defined, respectively, as not having or having a prescription for metformin in the baseline period. Discontinuation was assessed in all patients and adherence in patients who did not discontinue metformin. Factors predictive of discontinuation and adherence were assessed. ResultsDiscontinuation among new and ongoing users was 35.9% and 23.1%, respectively. Among the continuers of metformin treatment, the adherence rate was 40.5% and 44.3% among new and ongoing users, respectively. Among new users, baseline use of DDP-4 inhibitors (HR 1.276) and diabetes duration (HR 1.013) were associated with an increased risk of discontinuation, whereas increased age (HR 0.997), concomitant lipid-lowering therapy (HR 0.956), macrovascular disease (HR 0.952), and chronic kidney disease (HR 0.952) were associated with a decreased risk of discontinuation among ongoing users. Variables positively associated with adherence in both user groups were (HR values for all patients) age (1.021), smoking status (1.188), and baseline comorbidities: chronic kidney disease, depression, dementia, and chronic obstructive pulmonary disease (1.106, 1.192, 2.27, and 1.211, respectively), while obesity (0.936) and HbA1c 8.0–8.9% (0.862; reference <6.5%) were negatively associated with adherence. ConclusionsAbout one-third of patients initiating metformin discontinued within 12 months and fewer than 50% of all patients are adherent to metformin.

Abdominal aortic aneurysm: a review on the role of oral antidiabetic drugs.

A paradoxical negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) prevalence and growth is established. However, so far is not possible to determine whether this protection comes from the disease itself or the medication for Diabetes. The aim of this manuscript is to review the association between oral antidiabetic drugs and AAA incidence and growth. A search was conducted on PubMed and Scopus databases until December 2019 to identify publications reporting on the association between oral antidiabetic drugs (biguanides/metformin, sulfonylureas(SU), thiazolidinediones(TZD), dipeptidyl-peptidase 4(DPP-4) inhibitors, glucagon-like peptide 1(GLP-1) agonists, sodium-glucose transporter protein-2(SGLT2) inhibitors) and the outcomes AAA incidence and growth. Only data from human studies were considered, with a minimum of 3 months follow-up. Six studies enrolling 25,810 patients were included: one reporting on the AAA risk and five reporting on AAA growth. Metformin prescription was associated with a 28% reduction in AAA occurrence, while SU and TZD were associated with a 18% decrease in AAA risk. Regarding AAA enlargement, results were concordant for a slower expansion rate associated with metformin, with a decrease ranging from -0.30 mm/y to -1.30 mm/y, but not consistent for other antidiabetic drugs. Metformin seems to be associated with a decrease in AAA risk and enlargement rate. Evidence for the other classes is lacking. Studies evaluating the association between oral antidiabetic drugs and AAA progression, independently of the diabetic status, are needed.

Association Between Preoperative Metformin Exposure and Postoperative Outcomes in Adults With Type 2 Diabetes

Adults with comorbidity have less physiological reserve and an increased rate of postoperative mortality and readmission after the stress of a major surgical intervention. To assess postoperative mortality and readmission among individuals with diabetes with or without preoperative prescriptions for metformin. This cohort study obtained data from the electronic health record of a multicenter, single health care system in Pennsylvania. Included were adults with diabetes who underwent a major operation with hospital admission from January 1, 2010, to January 1, 2016, at 15 community and academic hospitals within the system. Individuals without a clinical indication for metformin therapy were excluded. Follow-up continued until December 18, 2018. Preoperative metformin exposure was defined as 1 or more prescriptions for metformin in the 180 days before the surgical procedure. All-cause postoperative mortality, hospital readmission within 90 days of discharge, and preoperative inflammation measured by the neutrophil to leukocyte ratio were compared between those with and without preoperative prescriptions for metformin. The corresponding absolute risk reduction (ARR) and adjusted hazard ratio (HR) with 95% CI were calculated in a propensity score-matched cohort. Among the 10 088 individuals with diabetes who underwent a major surgical intervention, 5962 (59%) had preoperative metformin prescriptions. A total of 5460 patients were propensity score-matched, among whom the mean (SD) age was 67.7 (12.2) years, and 2866 (53%) were women. In the propensity score-matched cohort, preoperative metformin prescriptions were associated with a reduced hazard for 90-day mortality (adjusted HR, 0.72 [95% CI, 0.55-0.95]; ARR, 1.28% [95% CI, 0.26-2.31]) and hazard of readmission, with mortality as a competing risk at both 30 days (ARR, 2.09% [95% CI, 0.35-3.82]; sub-HR, 0.84 [95% CI, 0.72-0.98]) and 90 days (ARR, 2.78% [95% CI, 0.62-4.95]; sub-HR, 0.86 [95% CI, 0.77-0.97]). Preoperative inflammation was reduced in those with metformin prescriptions compared with those without (mean neutrophil to leukocyte ratio, 4.5 [95% CI, 4.3-4.6] vs 5.0 [95% CI, 4.8-5.3]; P < .001). E-value analysis suggested robustness to unmeasured confounding. This study found an association between metformin prescriptions provided to individuals with type 2 diabetes before a major surgical procedure and reduced risk-adjusted mortality and readmission after the operation. This association warrants further investigation.

Abstract P444: Changes in Glucose-Lowering Medication Prescriptions After an Incident Cardiovascular Event Across eGFR Levels in an Integrated Health System

Introduction: Cardiovascular disease is a major complication among patients with diabetes, and may merit changes in both antihypertensive medications (e.g., to beta blockers and ACE inhibitors) and glucose-lowering medications (e.g., to sodium-glucose cotransporter 2 inhibitors [SGLT2i] and glucagon-like peptide 1 receptor agonists [GLP1 RA], medication classes with evidence of cardiovascular outcome benefit). The objective of this study was to assess how glucose-lowering medication prescriptions changed after a cardiovascular event among persons with diabetes. Hypothesis: There are changes in glucose-lowering medication prescription following a cardiovascular event. Methods: We identified adult patients with diabetes and estimated glomerular filtration rate (eGFR)≥15mL/min/1.73 m 2 who experienced a cardiovascular event (myocardial infarction, stroke, or heart failure) from 2005-2018 in the Geisinger Health System (cases). We selected control patients with diabetes but without a cardiovascular event by 1:1 matching on demographics, diabetes duration, HbA1c, eGFR, and calendar year. Results: In 15,918 matched case and control patients with diabetes (mean age 65 years, 52% female, mean HbA1c 7.55%, median diabetes duration 5.6 years, and 28% eGFR&lt;60 mL/min/1.73 m 2 ), insulin prescriptions increased and metformin prescriptions decreased after a cardiovascular event among cases compared with controls in all eGFR categories ( Table ). There were no differences between cases and controls with respect to changes in SGLT2i, GLP1 RA, or dipeptidyl peptidase 4 inhibitors (DPP4i). Conclusions: In a real-world setting, insulin prescriptions increased and metformin prescriptions decreased, after a cardiovascular event regardless of eGFR level. Prescriptions for SGLT2i and GLP1 RA did not change following a cardiovascular event in all eGFR categories. More efforts are needed to provide optimal therapies for cardiovascular risk reduction in patients with diabetes and cardiovascular disease.

Metformin adherence in patients with type 2 diabetes and its association with glycated haemoglobin levels.

INTRODUCTION Metformin is the initial medication of choice for most patients with type 2 diabetes. Non-adherence results in poorer glycaemic control and increased risk of complications. AIM The aim of this study was to characterise metformin adherence and association with glycated haemoglobin (HbA1c) levels in a cohort of patients with type 2 diabetes. METHODS Prescription and dispensing data were used for this study. Primary care clinical and demographic data were collected from 10 general practices (October 2016-March 2018) and linked to pharmaceutical dispensing information. Metformin adherence was initially measured by calculating the proportion of patients who had optimal medication cover for at least 80% of days (defined as a medication possession ratio (MPR) of ≥0.8), calculated using dispensing data. Prescription adherence was assessed by comparing prescription and dispensing data. The association between non-adherence (MPR <0.8) and HbA1c levels was also assessed. RESULTS Of the 1595 patients with ≥2 metformin prescriptions, the mean MPR was 0.87. Fewer Māori had an MPR ≥0.8 than New Zealand European (63.8% vs. 81.2%). Similarly, Māori received fewer metformin prescriptions (P=0.02), although prescription adherence did not differ by ethnicity. Prescription adherence was lower in younger patients (P=0.002). Mean HbA1c levels were reduced by 4.8 and 5.0mmol/mol, respectively, in all and Māori patients with an MPR ≥0.8. Total prescription adherence reduced HbA1c by 3.2mmol/mol (all P<0.01). DISCUSSION Ethnic disparity exists for metformin prescribing, leading to an overall reduction in metformin coverage for Māori patients. This needs to be explored further, including understanding whether this is a patient preference or health system issue.

A Safety Comparison of Metformin vs Sulfonylurea Initiation in Patients With Type 2 Diabetes and Chronic Kidney Disease: A Retrospective Cohort Study

ObjectiveTo compare the safety of metformin vs sulfonylureas in patients with type 2 diabetes by chronic kidney disease (CKD) stage. Patients and MethodsThis retrospective cohort study included adults in Manitoba, Canada, with type 2 diabetes, an incident monotherapy prescription for metformin or a sulfonylurea, and a serum creatinine measurement from April 1, 2006, to March 31, 2017. Patients were stratified by estimated glomerular filtration rate (eGFR) into the following groups: eGFR of 90 or greater, 60 to 89, 45 to 59, 30 to 44, or less than 30 mL/min/1.73 m2. Outcomes included all-cause mortality, cardiovascular events, and major hypoglycemic episodes. Baseline characteristics were used to calculate propensity scores and perform inverse probability of treatment weights analysis, and eGFR group was examined as an effect modifier for each outcome. ResultsThe cohort consisted of 21,996 individuals (19,990 metformin users and 2006 sulfonylurea users). Metformin use was associated with lower risk for all-cause mortality (hazard ratio [HR], 0.48; 95% CI, 0.40-0.58; P<.001), cardiovascular events (HR, 0.67; 95% CI, 0.52-0.86; P=.002), and major hypoglycemic episodes (HR, 0.14; 95% CI, 0.09-0.20; P<.001) when compared with sulfonylureas. CKD was a significant effect modifier for all-cause mortality (P=.002), but not for cardiovascular events or major hypoglycemic episodes. ConclusionSulfonylurea monotherapy is associated with higher risk for all-cause mortality, major hypoglycemic episodes, and cardiovascular events compared with metformin. Although the presence of CKD attenuated the mortality benefit, metformin may be a safer alternative to sulfonylureas in patients with CKD.

Cognitive Impairment in Diabetes - The Causality Association with Metformin

Background: As diabetic patients conventionally are on a long-term prescription for Metformin, it is important to identify any increase in their risk for developing cognitive disorders. An attempt was made here to study the cognitive impairment by using Montreal Cognitive Assessment test (MoCA) as a possible predictor of development of cognitive impairment in type 2 diabetics on metformin therapy. Methods: 400 Type 2 diabetics on Metformin containing anti diabetic regimen were enrolled from2016-2018. Data was recorded, cognitive test MoCA was administered, and a score below 26 considered abnormal. Results: The participants on metformin had a mean MoCA score of 20.17±2.06, while those on other drugs had a mean score of 21.11±3.06. Thus, metformin use has significant impact on the cognitive abilities of its user. Conclusions: Amongst patients receiving medical therapy for control of type 2 diabetes, participants using metformin showed a very high prevalence rate of abnormal MoCA scores (85%). Funding Statement: The author declares: Nil. Declaration of Interests: The author states: There is no conflict of interest. Ethics Approval Statement: This study was approved by Manipal University Institutional Ethics Committee, Kasturba Medical College.

Metformin Prescription is Associated with Reduced AAA Growth Rate in a European Cohort

Metformin Prescription is Associated with Reduced AAA Growth Rate in a European Cohort

Type 2 Diabetes Prescribing Habits amongst Providers to an Underserved Population.

Type 2 diabetes mellitus (T2DM) affected over 30 million individuals in the United States as of 2015. Due to the national diabetes guidelines recommending drug selection based on several patient specific factors and varying formulary restrictions, prescribers are often inundated when selecting treatment. Currently, limited evidence is available regarding the primary factors influencing prescribers' drug therapy selection. The purpose of this study was to identify factors that influence providers during T2DM medication selection. The study was conducted with providers at a large, academic, safety net health system. All prescribers were sent an electronic, optional and anonymous survey. Prescribers treating T2DM in non-pregnant adult patients were the only prescribers assessed. Factors evaluated were: cost, A1c, comorbidities, adherence, weight, tolerability, patient limitations, and use of guidelines. A total of 86 prescribers responded, yielding a response rate of 31%. The respondents included physicians (56.3%), nurse practitioners (21.8%), medical residents (18.4%), and fellows (3.4%); with the majority practicing in internal or family medicine (47.1%). The most frequently prescribed T2DM medications included: metformin (83.8%), insulin (78.1%), and sulfonylureas (64.8%). Cost and A1c elevation were two of the major factors influencing prescribing of metformin (94.1% and 81.2%), insulin (57.4% and 69.6%), and sulfonylureas (81.2% and 89.9%) respectively. Due to cost concerns, respondents reported rarely or never prescribing glucagon-like peptide-1 agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) despite recognizing benefits on diabetes related comorbidities. Although current literature from the national guidelines encourages the use of GLP-1RA and SGLT2i as first-line options after metformin in T2DM, these classes of medications were not reported among the most commonly prescribed despite providers correctly identifying positive medication attributes such as cardio- and nephroprotection and weight loss. However, cost of these medications appears to outweigh the benefits when selecting medication therapy.

Association between long-term prescription of metformin and the progression of heart failure with preserved ejection fraction in patients with type 2 diabetes mellitus and hypertension

BackgroundType 2 diabetes mellitus (T2DM) and hypertension are independently related to increasing risk of subsequent incident heart failure with preserved ejection fraction (HFpEF). This study was designed to evaluate the influences of long-term metformin prescription in these patients. MethodsUsing a propensity score matching of 1:2 ratio, this retrospective claims database study compared metformin prescription (n = 130) and non-metformin therapy (n = 260) in patients with T2DM and hypertension and without clinical signs or symptoms of heart failure. ResultsWith a follow-up of 6 years, the new-onset symptomatic HFpEF occurred in 6 of 130 patients in metformin group and 31 of 260 patients in non-metformin group (P = .020). Metformin also generated more prominent improvement in left ventricular (LV) diastolic function and hypertrophy. And Cox proportional hazards regression model revealed that metformin prescription (HR 0.351, 95% CI: 0.145–0.846, P = .020) was associated with a reduced risk of new onset of symptomatic HFpEF. ConclusionsLong-term metformin exposure was associated with protective effects in terms of the incidence of new-onset symptomatic HFpEF, LV diastolic dysfunction and hypertrophy in patients with T2DM and hypertension, which might be beneficial for the delay of HFpEF progression.

Association Between Antidiabetic Medications and Prostate-Specific Antigen Levels and Biopsy Results

Diabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear. To examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy. Population-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019. One or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register. Levels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression. The cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy. This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.

Impact of metformin on the risk and treatment outcomes of tuberculosis in diabetics: a systematic review

BackgroundTuberculosis (TB) remains one of the infectious diseases with a leading cause of death among adults worldwide. Metformin, a first-line medication for the treatment of type 2 diabetes, may have potential for treating TB. The aims of the present systematic review were to evaluate the impact of metformin prescription on the risk of tuberculosis diseases, the risk of latent TB infection (LTBI) and treatment outcomes of tuberculosis among patients with diabetic mellitus.MethodsDatabases were searched through March 2019. Observational studies reporting the effect of metformin prescription on the risk and treatment outcomes of TB were included in the systematic review. We qualitatively analyzed results of included studies, and then pooled estimate effects with 95% confidence intervals (CIs) of different outcome using random-effect meta-analyses.ResultsThis systematic review included 6980 cases from 12 observational studies. The meta-analysis suggested that metformin prescription could decrease the risk of TB among diabetics (pooled odds ratio [OR], 0.38; 95%CI, 0.21 to 0.66). Metformin prescription was not related to a lower risk of LTBI (OR, 0.73; 95%CI, 0.30 to 1.79) in patients with diabetes. Metformin medication during the anti-tuberculosis treatment is significantly associated with a smaller TB mortality (OR, 0.47; 95%CI, 0.27 to 0.83), and a higher probability of sputum culture conversion at 2 months of TB disease (OR, 2.72; 95%CI, 1.11 to 6.69) among patients with diabetes. The relapse of TB was not statistically reduced by metformin prescription (OR, 0.55; 95%CI, 0.04 to 8.25) in diabetics.ConclusionsAccording to current observational evidence, metformin prescription significantly reduced the risk of TB in patients with diabetes mellitus. Treatment outcomes of TB disease could also be improved by the metformin medication among diabetics.

P2547Statin and glucose-lowering treatment in individuals with and without schizophrenia

Abstract Background We have recently shown that Cardiovascular (CV) mortality is surprisingly high in patients with schizophrenia in Sweden. Diabetes is 2–3 times more common in patients with schizophrenia. Treatment with Metformin have consistently shown effective to lower CV mortality in patients with diabetes. In addition, recent studies have shown that treatment with Metformin reduces weight and improves lipids even in patients with schizophrenia without diabetes. One reason for the high CV mortality in Swedish patients with schizophrenia may be lack of risk factor treatment, such as glucose-lowering treatment and/or lipid lowering treatment with statins. Objective To determine the prevalence of treatment with glucose-lowering treatment and statins in patients with and without schizophrenia in Stockholm, Sweden. Material and methods Cross-sectional study based on individual-level patient data from the Stockholm regional health-care data warehouse. 6 347 patients with a diagnosis of schizophrenia (International Classification of Diseases, Tenth Revision code F 20.X) were compared with 2 062 112 without schizophrenia from Stockholm County. The prescription of Metformin and insulin were compared in 5-year age groups from 30 to 85 years of age. In addition, the prescription of statins (any statin) were also compared in the same population. Results The prescription of metformin in age groups under 60 years were approximately 2 to 8 times more common in patients with schizophrenia, in patients over 60 the corresponding figures were 0.7 to 3 times. The prescription of statin in age groups under 60 were approximately 0.8–3 times more common in patients with schizophrenia. In contrast, in patients over 60 years statins were less often prescribed in patients with schizophrenia compared to controls. Figure 1 Conclusions Our results indicate that lack of treatment with metformin may not be a reason for the increase cardiovascular mortality in patients with schizophrenia. However, the surprisingly low prescription of statins in older (&gt;60 years) patients with schizophrenia might explain the high CV mortality in this patient group.

Factors associated with clinical inertia in type 2 diabetes mellitus patients treated with metformin monotherapy

Aims: To assess demographic and clinical characteristics associated with clinical inertia in a real-world cohort of type 2 diabetes mellitus patients not at hemoglobin A1c goal (<7%) on metformin monotherapy.Methods: Adult (≥18 years) type 2 diabetes mellitus patients who received care at Massachusetts General Hospital/Brigham and Women’s Hospital and received a new metformin prescription between 1992 and 2010 were included in the analysis. Clinical inertia was defined as two consecutive hemoglobin A1c measures ≥7% ≥3 months apart while remaining on metformin monotherapy (i.e. without add-on therapy). The association between clinical inertia and demographic and clinical characteristics was examined via logistic regression.Results: Of 2848 eligible patients, 43% did not achieve a hemoglobin A1c goal of <7% 3 months after metformin monotherapy initiation. A sub-group of 1533 patients was included in the clinical inertia analysis, of which 36% experienced clinical inertia. Asian race was associated with an increased likelihood of clinical inertia (OR = 2.43; 95% CI = 1.48–3.96), while congestive heart failure had a decreased likelihood (OR = 0.58; 95% CI = 0.32–0.98). Chronic kidney disease and cardiovascular/cerebrovascular disease had weaker associations but were directionally similar to congestive heart failure.Conclusions: Asian patients were at an increased risk of clinical inertia, whereas patients with comorbidities appeared to have their treatment more appropriately intensified. A better understanding of these factors may inform efforts to decrease the likelihood for clinical inertia.

Evaluation of weight change and hypoglycaemia as mediators in the association between insulin use and death.

To evaluate whether weight change or hypoglycaemia mediates the association between insulin use and death. In a retrospective cohort of veterans who filled a new prescription for metformin and added insulin or sulphonylurea (2001-2012), we assessed change in body mass index (BMI) and hypoglycaemia during the first 12 months of treatment intensification. Cox proportional hazards models compared the risk of death between treatment groups. Using the difference method, we estimated the indirect effect and proportion mediated through each mediator. A sensitivity analysis assessed mediators in the first 6 months of intensified therapy. Among 28 892 patients surviving 12 months, deaths per 1000 person-years were 15.4 for insulin users and 12.9 for sulphonylurea users (HR 1.20, 95% CI 0.87, 1.64). Change in BMI and hypoglycaemia mediated 13% (-98, 98) and -1% (-37, 71) of this association, respectively. Among 30 214 patients surviving 6 months, deaths per 1000 person-years were 34.8 for insulin users and 21.3 for sulphonylurea users (HR 1.66, 95% CI 1.28, 2.15). Change in BMI and hypoglycaemia mediated 9% (1, 23) and 0% (-9, 4) of this association, respectively. We observed an increased risk of death among metformin users intensifying treatment with insulin versus sulphonylurea and surviving 6 months of intensified therapy, but not among those surviving 12 months. This association was mediated in part by weight change.

User-Centered Development of a Behavioral Economics Inspired Electronic Health Record Clinical Decision Support Module.

Changing physician behaviors is difficult. Electronic health record (EHR) clinical decision support (CDS) offers an opportunity to promote guideline adherence. Behavioral economics (BE) has shown success as an approach to supporting evidence-based decision-making with little additional cognitive burden. We applied a user-centered approach to incorporate BE “nudges” into a CDS module in two “vanguard” sites utilizing: (1) semi-structured interviews with key informants (n=8); (2) a design thinking workshop; and (3) semi-structured group interviews with clinicians. In the 133 day development phase at two clinics, the navigator section fired 299 times for 27 unique clinicians. The inbasket refill alert fired 124 times for 22 clinicians. Fifteen prescriptions for metformin were written by 11 clinicians. Our user-centered approach yielded a BE- driven CDS module with relatively high utilization by clinicians. Next steps include the addition of two modules and continued tracking of utilization, and assessment of clinical impact of the module.