Metformin Prescription Research Articles

MP14-14 EFFECT OF METFORMIN USE ON PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History III1 Apr 2015MP14-14 EFFECT OF METFORMIN USE ON PROSTATE CANCER Abdo Kabarriti, Ben Boursi, Ronac Mamatani, Thomas Guzzo, Kevin Haynes, Yu-Xiao Yang, and S. Bruce Malkowicz Abdo KabarritiAbdo Kabarriti More articles by this author , Ben BoursiBen Boursi More articles by this author , Ronac MamataniRonac Mamatani More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , Kevin HaynesKevin Haynes More articles by this author , Yu-Xiao YangYu-Xiao Yang More articles by this author , and S. Bruce MalkowiczS. Bruce Malkowicz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.876AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Observational studies have demonstrated that Metformin use decreases the risk of breast, pancreatic, liver, lung, and colon cancer. We sought to evaluate the association between Metformin use and prostate cancer risk. METHODS We conducted a nested case-control study using The Health Improvement Network (THIN) database, a large primary care database from the UK. Study cases were defined as those with any diagnostic code for prostate cancer. Index date was defined as the time of prostate cancer diagnosis. Each case was matched with up to four eligible controls on age, sex, practice site, calendar time and duration of follow-up before index date using incidence density sampling. Exposure of interest was metformin therapy beginning more than one year before index date. The odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer associated with metformin use were estimated using conditional logistic regression analysis, adjusted for BMI, smoking history, diabetes mellitus, number of previous urinary tract infections and the use of other anti-diabetic therapy. RESULTS The case-control analysis included 27,212 prostate cancer patients and 105,940 controls. 4.1% (1,122) of cases were current metformin users, compared to 5% (5,234) of controls. 0.9% (247) of case and 0.9% (976) of controls were past metformin users, with last prescription more than 6 months before index date. The adjusted odds ratio for prostate cancer among current and past metformin users was 0.86 (95% CI 0.79-0.94, p=0.001) and 1.02(0.87-1.2, p=0.8), respectively. There was no association between first metformin prescription date or cumulative duration of therapy and prostate cancer risk. The adjusted odds ratios for cumulative duration quartiles were 0.81(0.58-1.12, p=0.2), 0.86(0.75-0.97, p=0.02), 0.86(0.76-0.98, p=0.02), and 0.87(0.76-0.99, p=0.03) for 0–25%, 25–50%, 50–75% and 75–100%, respectively. CONCLUSIONS Current Metformin use is associated with a significant decreased risk of prostate cancer. This is consistent with the protective effects found in metformin users and other cancers. Exact mechanism responsible for the risk reduction needs to be elucidated. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e156 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Abdo Kabarriti More articles by this author Ben Boursi More articles by this author Ronac Mamatani More articles by this author Thomas Guzzo More articles by this author Kevin Haynes More articles by this author Yu-Xiao Yang More articles by this author S. Bruce Malkowicz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Self-denigration in pharmacy.

In response to the editorials by Drs. Davies and Tsuyuki on self-denigrating words and actions in pharmacy,1,2 I do agree that change is required, at the grassroots level, but I don’t agree with some of the statements made by the authors. Many of the issues highlighted as self-denigrating relate to factors that are in many respects uncontrollable for most community pharmacists, that is, the nature of the environment itself. And while one may state “that’s why we should limit ownership to pharmacists,” this is in place in Australia yet the same “issues” are present. The definition of allied is “joined in a relationship in which people, groups, countries, etc., agree to work together”3—what’s wrong with this term? I don’t believe it connotes a secondary role. As well, I’m not sure how many pharmacists would ever refer to themselves as “retail” pharmacists; it’s either pharmacist or community pharmacist. Those who work in a hospital are almost always sure to distinguish themselves as hospital pharmacists. “Minor ailments” do not mean “insignificant” ailments, and this term is integrated into legislation in many jurisdictions.4,5 By pledging to avoid the term minor ailment in CPJ going forward, does this mean that those in the profession wanting to disseminate findings on these ailments in various jurisdictions must look to publish elsewhere? With regard to drive-through pharmacies, I too used to think they served no purpose in community pharmacy practice, until someone asked me where I would prefer to have counselling done on a potentially embarrassing condition—in the pharmacy itself, with other patients right behind me, or in the privacy of my own vehicle? Furthermore, if you were a parent with a child who had otitis media and was in pain, wouldn’t you rather stay in your own vehicle with your child (or children) while the antibiotic was being filled? The environment of the community pharmacy itself is what dictates many of the “stereotypes” mentioned in the editorials. How many physicians or dentists provide the opportunity to purchase pop, chips, chocolate bars and other unhealthy fare along with a metformin prescription and a professional health care service? This retail environment means that patients do not always see themselves that way, with as many as two-thirds of patients viewing themselves as customers.6-8 Perhaps the profession would be best served by professional and advocacy organizations arming individual pharmacists with the tools and resources to advocate for better recognition of what pharmacists are and can do, highlighting the true value of pharmacists. There are examples of pharmacists going to politicians and providing professional services to inform them of the role pharmacists play and the value of pharmacists9,10 and of organizations that provide grassroots advocacy resources for pharmacists, turning them into frontline advocates.11,12 Instead of saying that the medication review you just completed for a patient is “free,” why not let the patient know the value the government has placed on the service (e.g., $60)? Why not invite your local MP, MLA, MPP or municipal leaders into your pharmacy to show them what pharmacists are doing and where they add value to patients and the system? This would help develop and nurture a long-term relationship. Being reactive instead of proactive will almost always result in a less than desirable outcome and will use a lot more resources.

Capitalizing on Prescribing Pattern Variation to Compare Medications for Type 2 Diabetes

BackgroundClinical trials often compare hypoglycemic medications on the basis of glycemic control but do not examine long-term outcomes (e.g., mortality). This study demonstrates an alternative approach to lengthening clinical trials to assess these long-term outcomes. ObjectiveTo use observational quasi-experimental methods using instrumental variables (IVs) to compare the effect of two hypoglycemic medications, sulfonylureas (SUs) and thiazolidinediones (TZDs), on long-term outcomes. MethodsThis study used administrative data from the Veterans Health Administration and Medicare from 2000 to 2010. The study population included US veterans dually enrolled in Medicare who received a prescription for metformin and then initiated SUs or TZDs. Patients could either continue on or discontinue metformin after the initiation of the second agent. Treatment was defined as starting either a SU or a TZD. Local variations in SU prescribing rates were used as instruments in IV models to control for selection bias. Survival models predicted all-cause mortality, ambulatory care sensitive condition hospitalizations, and stroke or heart attack (acute myocardial infarction). ResultsStarting on SUs compared to TZDs significantly increased the likelihood of experiencing mortality and ACSC hospitalization. The estimated hazard ratio for the effect of starting on SUs compared to TZDs was 1.50 (95% confidence interval [CI] 1.09–2.09) for all-cause mortality, 1.68 (95% CI 1.31–2.15) for ambulatory care sensitive condition hospitalization, and 1.15 (95% CI 0.80–1.66) for acute myocardial infarction or stroke. ConclusionsOur findings suggest increased risk of major adverse events associated with SUs as a second-line agent. Quasi-experimental IV methods may be an important alternative to lengthening clinical trials to assess long-term outcomes.

Medication safety and chronic kidney disease in older adults prescribed metformin: a cross-sectional analysis.

BackgroundMedication safety in patients with chronic kidney disease (CKD) is a growing concern. This is particularly relevant in older adults due to underlying CKD. Metformin use is contraindicated in patients with abnormal kidney function; however, many patients are potentially prescribed metformin inappropriately. We evaluated the prevalence of CKD among older adults prescribed metformin for type 2 diabetes mellitus using available equations to estimate kidney function and examined demographic characteristics of patients who were potentially inappropriately prescribed metformin.MethodsWe conducted a cross-sectional analysis of older adults aged ≥65 years prescribed metformin from March 2008-March 2009 at an urban tertiary-care facility in Seattle, Washington, USA. CKD was defined using National Kidney Foundation-Kidney Disease Outcomes Quality Initiative criteria. Creatinine clearance was calculated using the Cockcroft-Gault equation; estimated glomerular filtration rate was calculated using the abbreviated Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology (EPI) Collaboration equations. Regression analyses were used to determine the associations between demographic characteristics and prevalent CKD.ResultsAmong 356 subjects (median age 69 years, 52.5% female, 39.4% non-Hispanic black), prevalence of stage 3 or greater CKD calculated by any of the equations was 31.4%. The Cockcroft-Gault equation identified more subjects as having CKD (23.7%) than the abbreviated MDRD (21.1%) or CKD-EPI (21.7%) equations (P < 0.001). Older age (OR = 1.13, 95% CI 1.08-1.19) and female sex (OR = 2.51, 95% CI 1.44-4.38) were associated with increased odds of potentially inappropriate metformin prescription due to CKD; non-Hispanic black race was associated with decreased odds of potentially inappropriate metformin prescription due to CKD (OR = 0.41, 95% CI 0.23-0.71).ConclusionsCKD is common in older adults prescribed metformin for type 2 diabetes, raising concern for potentially inappropriate medication use. No single equation to estimate kidney function may accurately identify CKD in this population. Medication safety deserves greater consideration among elderly patients due to the widespread prevalence of CKD.

Contraindicated metformin prescriptions in German type 2 diabetics: Data from a general population based study. Is metformin therapy carried out critically enough?

Contraindicated metformin prescriptions in German type 2 diabetics: Data from a general population based study. Is metformin therapy carried out critically enough?

Improved metabolic response after 16 weeks of calorie-restricted low-glycaemic index diet and metformin in impaired glucose tolerance subjects.

This study analyzed the metabolic effects of dietary advice to follow calorie-restricted low-glycaemic index diet with metformin in overweight / obese impaired glucose tolerance subjects. Sixteen subjects with body mass index between 27-38 kg/m² were followed monthly for 16 weeks and treated with metformin (1 g/day) and dietary prescription for low-glycaemic index diet with energy reduction of 25-30% their total energy expenditure. Glucose metabolism, lipid profile, anthropometric and body composition, and food intake parameters were measured before and after the treatment. Paired t-tests/Wilcoxon tests were used to compare differences from baseline, with a statistical significance criterion of p ≤0.05. There were significant reductions in anthropometric and body composition parameters, decrease in HOMA2-%betaand triglycerides concentrations, and increase in Cederholm index. These results show enhanced peripheral insulin sensitivity and preservation of pan - creatic beta-cell function. Calorie-restricted low-glycaemic index diet and metformin was benefit to metabolic and anthropometric parameters in overweight/obese subjects with impaired glucose tolerance.

Abstract P3-06-01: Association between metformin use and improved survival in breast cancer patients: A population-based study

Abstract Background: Long-term use of AMP-kinase agonist Metformin, the first-line oral hypoglycemic agent, has recently been shown to be associated with both a decreased incidence of and improved survival following diagnosis of breast and other solid tumors. However, the sample size of most reported studies has been limited and has not been able to clearly delineate if there are molecular subtype-dependent effects. Method: We implemented a population-based, retrospective case-control analysis of the effect of metformin on breast cancer outcomes. We comprehensively searched the electronic medical records of all female patients who were cared for within the University of Pennsylvania Health System between the years 1997 and 2013. To ensure the accuracy of patient selection, we focused our preliminary analysis on only patients (n = 20,684) who received an ICD9 code for breast cancer (BC) on at least 2 separate in-person visits. We assessed the use of metformin by identifying those patients who have at least a record of a metformin prescription both before the first breast cancer diagnosis ICD9 code and after the first breast cancer diagnosis visit. Overall survival was determined by assessing a combination of electronic medical record of patient expiration and the SSN Death Certificate Index. Statistical tests, including chi-sq and cox-hazard modeling were implemented in R, Graphpad Prism or EXCEL. Results: In the preliminary analysis, we identified a total of 29,251 female patients either diagnosed or reported a history of BC within the UPHS EMRs. Stratifying by per patient visits, we limited the subsequent analysis to the 20,684 BC patients with at least 2 in-person visits where BC was recorded as a diagnosis code. Of these, there were 534 patients who had a record of metformin prescription prior to and after the first BC diagnosis code and 20,150 BC patients who did not. We found that with a mean follow up of (6.40 years), there were a total of 8 deaths (1.28%) in metformin users and 526 deaths (2.62%) among the no metformin users. Using a two-tailed chi-sq test, we found that metformin use was significantly associated with improved overall survival rates (98.50 vs 96.94%, p&amp;lt;0.05). We are currently assessing the role of age, ethnicity, the presence of diabetes, health metrics related to insulin resistance, and the use of other metabolic regulators (insulin, sulfonylurea) using a cox-hazard proportional risk model. Conclusion: Our preliminary analyses suggest that metformin use before and following diagnosis may be protective against overall mortality among women diagnosed with breast cancer. A more refined Cox proportional hazard modelling is ongoing, which will shed light on how factors such as the use of other metabolic agents, age, and breast cancer subtype may interact with metformin's effect on overall and disease-free BC survival. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-06-01.

A quantitative measure of diabetes risk in community practice impacts clinical decisions: The PREVAIL initiative

Background and aimsWhile predictive tools are being developed to identify those at highest risk for developing diabetes, little is known whether these assays affect clinical care. Methods and resultsThirty sites who used the PreDx® (Tethys BioScience, Emeryville, CA) abstracted clinical information from baseline clinic visits prior to a PreDx test and from the most recent visit at time of abstraction. All visits occurred between May 2008–April 2011 (median follow-up 198 days, IQR 124–334). The primary analysis was the influence of the PreDx test (5-year diabetes prediction) on subsequent care; descriptive statistics were used to summarize baseline and follow-up variables. Overall 913 patients with 2 abstracted visits were included. Relative to baseline, median SBP decreased 1.5 mmHg (p = 0.039), DBP decreased 2 mmHg (p < 0.001), LDL-C decreased 4 mg/dL (p = 0.009), and HDL-C increased 2 mg/dL (p < 0.001) at follow-up. Behavioral or lifestyle counseling was not significantly different from baseline to follow-up (71.2% vs. 68.1% (p = 0.077), but BMI was lower by 0.2 kg/m2 at follow up (p = 0.013). At follow-up, more patients were prescribed metformin (13.7% vs. 9.7%, p < 0.001). A higher PreDx score was significantly associated with metformin prescription (p = 0.0003), lifestyle counseling (p = 0.0099), and a lower BMI at follow-up (p = 0.007). ConclusionThe use of a prognostic test in patients perceived to be high risk for diabetes was associated with a modest but significant increase in the prescription of metformin and lifestyle interventions and a reduction in BMI.

The comparative risk of new-onset diabetes after prescription of drugs for cardiovascular risk prevention in primary care: a national cohort study

ObjectiveRecent studies suggest that statins increase the risk of subsequent diabetes with a clear dose response effect. However, patients prescribed statins have a higher background risk of diabetes. This national...

Abnormal Vaginal Bleeding Following Pharmacist Prescribing of Metformin Leads to the Detection of Complex Endometrial Hyperplasia

To describe a case where pharmacist prescribing of metformin therapy resulted in unexplained vaginal bleeding in a patient later diagnosed with complex endometrial hyperplasia. A 57-year-old woman with diagnoses of hypertension and dyslipidemia was assessed by a pharmacist with prescribing authorization for hypertension management. Cardiovascular risk assessment performed by the pharmacist resulted in the detection of metabolic syndrome confirmed by the patient's physician. The pharmacist prescribed metformin 500 mg twice daily for prediabetes and metabolic syndrome, resulting in vaginal bleeding 1 week following initiation of therapy. Bleeding stopped following discontinuation of metformin, and recurred on retrial. The symptoms were dose dependent as bleeding did not occur at a dose of 500 mg once daily, but recurred at a total dose of 1000 mg/d. The patient was referred for physical examination and endometrial ultrasound and sampling, and was found to have complex endometrial hyperplasia. Metformin is widely used for the treatment of polycystic ovary syndrome as it improves ovulation and menstrual cycle regularity. In this case, the patient was not known to have polycystic ovary syndrome but was instead provided metformin for metabolic syndrome and hyperinsulinemia. It is believed that metformin's endocrine effects resulted in the sloughing of this hyperplastic tissue, prompting the pharmacist to refer the patient for medical assessment. This case is unique as it is the first of our knowledge to report a scenario where pharmacist prescribing resulted in facilitated detection of a previously undetected disease, highlighting that an expanded scope of practice for pharmacists can facilitate disease diagnosis when collaboration occurs among health professionals. Female patients initiated on metformin therapy should be aware that any changes to their menstrual cycle following metformin may indicate endometrial disease. Additionally, pharmacist prescribing for chronic disease management, when practiced collaboratively with the patient and their physician, can facilitate disease detection through effective referral and follow-up.

Prescribing of antidiabetic therapies in Ireland: 10-year trends 2003–2012

Over the last decade there have been significant changes in the prescribing of antidiabetic therapies. It is of interest to know about these trends and variations in the Irish population so that future prescribing patterns can be estimated. To examine the trends in prescribed antidiabetic treatments, including variations across age, gender, socioeconomic status and regions in the Irish population over the last 10 years. The Irish national pharmacy claims database was used to identify patients ≥ 16 years dispensed antidiabetic agents (oral or insulin) from January 2003 to December 2012 through the two main community drug schemes for diabetes. The rate of prescribing per 1,000 population was calculated. Logistic regression was used to examine variations in prescribing in patients with diabetes. There was a significant increase in the prescribing of fast and long-acting insulin analogues with a rapid decline in the prescribing of human insulin (p < 0.0001). Increased prescribing of metformin, incretin modulators and fixed oral combination agents was observed (p < 0.0001). Females and older aged patients were more likely to be prescribed human insulin than other insulins. Metformin was less likely while sulphonylureas were more likely to be prescribed in older than younger aged patients. Socioeconomic differences were observed in increased prescribing of the newer and more expensive antidiabetic agents in the non-means tested scheme. Regional variations were observed in the prescribing of both insulin and oral antidiabetic agents. There has been an increase over time in the prescribing of both insulin and oral antidiabetic agents in the Irish population with increasing uptake of newer antidiabetic agents. This has implications for projecting future uptake and expenditure of these agents given the rising level of diabetes in the population.

Annual Medical Costs of Swedish Patients with Type 2 Diabetes Before and After Insulin Initiation.

IntroductionAlthough insulin is one of the most effective interventions for the treatment of type 2 diabetes, its disadvantages incur substantial medical cost. This study was designed to evaluate the medical costs of Swedish type 2 diabetic patients initiating insulin on top of metformin and/or sulfonylurea (SU), and to evaluate if costs before and after insulin initiation differ for patients where insulin is initiated above or below the recommended glycosylated hemoglobin (HbA1c) level (7.5%).MethodsThis was a register-based retrospective cohort study in which patients were identified from the Sörmland county council diabetes register. Patients being prescribed at least one prescription of metformin and/or SU from 2003 to 2010, and later prescribed insulin, were included.ResultsOne hundred patients fulfilled the inclusion criteria and had at least 1 year of follow-up. The mean age was 61 years and 59% of patients were male. Mean time since diagnosis was 4.1 years, and since initiation of insulin was 2.2 years. The mean HbA1c level at index date was 8.0%. Total mean costs for the whole cohort were SEK 17,230 [standard deviation (SD) 17,228] the year before insulin initiation, and SEK 31,656 (SD 24,331) the year after insulin initiation (p < 0.0001). When stratifying by HbA1c level, patients with HbA1c <7.5% had total healthcare costs of SEK 17,678 (SD 12,946) the year before the index date and SEK 35,747 (SD 30,411) the year after (p < 0.0001). Patients with HbA1c levels ≥7.5% had total healthcare costs of SEK 16,918 (SD 19,769) the year before the index date and SEK 28,813 (SD 18,779) the year after (p < 0.0001).ConclusionDespite the small sample size, this study demonstrates that mean annual medical costs almost double the year after patients are initiated on insulin. The costs increased the year after insulin initiation, regardless of the HbA1c level at initiation of insulin, and the largest increase in costs were due to increased filled prescriptions.

Assessment of Serum Creatinine and Kidney Function among Incident Metformin Users

Metformin is considered the first-line antihyperglycemic therapy for type 2 diabetes, but should be used with caution in people with renal insufficiency. Our study objective was to describe the proportion of patients who have an assessment of kidney function (serum creatinine [SCr] and estimated glomerular filtration rate [eGFR]) around the time of initiation of metformin in new users. We used data from the Alberta Kidney Disease Network to identify patients with diabetes (age, ≥66 y) with a new prescription for metformin from November 1, 2002, to March 31, 2008. We assessed whether SCr measurement was completed before and after metformin initiation. The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and categorized into CKD stages. Frequency of metformin use based on SCr measurement and CKD stage was reported using descriptive statistics. A total of 22 051 subjects were identified as new metformin users. Overall, 25.4% (n=5608) had no measurement of SCr or assessment of eGFR before metformin prescription. In addition, of patients with an eGFR measurement, 38.7% (n=8544) of individuals had an eGFR of less than 60 mL/min/1.73 m(2). One quarter of patients started on metformin did not have a SCr measurement completed beforehand. Also, metformin was used commonly among patients with diabetes and CKD, potentially putting these individuals at risk for adverse events.

Preadmission metformin use and mortality among intensive care patients with diabetes: a cohort study

IntroductionMetformin has anti-inflammatory and anti-thrombotic effects that may improve the outcome of critical illness, but clinical data are limited. We examined the impact of preadmission metformin use on mortality among intensive care unit (ICU) patients with type 2 diabetes.MethodsWe conducted this population-based cohort study among all persons admitted to the 17 ICUs in Northern Denmark (population approximately 1.8 million). We focused on all patients with type 2 diabetes who were admitted to the ICUs between January 2005 and December 2011. Through individual-level linkage of population-based medical databases, type 2 diabetes was identified using a previously validated algorithm including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and elevated HbA1c levels. Metformin use was identified by filled prescriptions within 90 days before admission. Covariates included surgery, preadmission morbidity, diabetes duration, and concurrent drug use. We computed 30-day mortality and hazard ratios (HRs) of death using Cox regression adjusted for covariates, both overall and after propensity score matching.ResultsWe included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%) filled a prescription for metformin as monotherapy within 90 days before admission and 1,335 (18.0%) received metformin in combination with other anti-diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users, 17.9% among metformin combination therapy users, and 25.0% among metformin non-users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin combination therapy users, compared to non-users. Propensity-score-matched analyses yielded the same results. The association was evident across most subgroups of medical and surgical ICU patients, but most pronounced in elderly patients and in patients with well-controlled diabetes. Former metformin use was not associated with decreased mortality.ConclusionsPreadmission metformin use was associated with reduced 30-day mortality among medical and surgical intensive care patients with type 2 diabetes.

Pharmacology and safe prescribing of metformin

Metformin is thought to exert its antihyperglycaemic effect through the activation of adenosine monophosphate-activated protein kinase enzyme, which is expressed in many tissues. This results in the lowering of blood glucose level in patients with diabetes. Its positive impact on the macrovascular complications of diabetes, good safety profile and wide patient acceptability has established its position as a first-line diabetes medication. Adverse effects associated with its use are generally mild and usually involve transient gastrointestinal symptoms. Lactic acidosis is rare and can be avoided by strict adherence to prescribing guidelines.

Initial sulfonylurea use and subsequent insulin therapy in older subjects with type 2 diabetes mellitus.

BackgroundIn type 2 diabetes mellitus (T2DM), progressive loss of beta cell function over time requires treatment intensification and eventually initiation of insulin for many patients. Relative to metformin, a greater rate of decline in beta cell function over time has been observed with sulfonylurea treatment. The present study examined the association between initial monotherapy with metformin or sulfonylurea and subsequent initiation of insulin in older subjects with T2DM.MethodsIn a retrospective cohort study using the GE electronic medical record database, eligible subjects with T2DM included those ≥65 years who received their first prescription of sulfonylurea or metformin as initial monotherapy between January 1, 2003 to December 31, 2008. The follow-up period lasted to the end of 2009 or the subject’s latest data available. Insulin initiation was determined by prescription records. Logistic regression analysis evaluated the likelihood of insulin addition. A Cox regression model estimated time to initiation of insulin. Differences in baseline characteristics were controlled for using propensity score matching.ResultsOverall, 12,036 subjects were included in the analysis. Mean age was 75 years and 50% were male. Subjects who initiated with sulfonylurea had a significantly (P < 0.001) higher incidence of insulin addition (2.8% vs. 1.4%) compared to those initiated with metformin within 1 year of follow-up. The likelihood of initiating insulin was higher in subjects initiated with sulfonylurea than with metformin (adjusted odds ratio 1.82, 95% confidence interval [CI] 1.40–2.38; P < 0.001). Sulfonylurea use was also significantly associated with a shorter time to insulin use compared to metformin (adjusted hazards ratio 2.10, 95% CI 1.83–2.39; P < 0.001).ConclusionIn a cohort of older subjects with T2DM initiating antihyperglycemic therapy, new users of sulfonylurea monotherapy were more likely to receive insulin therapy and received it earlier than those starting with metformin.

Use of Computer Alerts to Prevent the Inappropriate Use of Metformin in an Inpatient Setting

Metformin is recommended as initial therapy for most patients with type 2 diabetes mellitus. Its most serious adverse effect, lactic acidosis, is a rare entity with a high mortality rate. Despite well-publicized contraindications, metformin is inappropriately prescribed to many hospitalized patients. To determine the efficacy of computer alerts at reducing inappropriate metformin prescribing. Retrospective chart review of all hospitalized patients who received an order for metformin, before (n = 144) and after (n = 147) an intervention designed to reduce inappropriate administration. This intervention included 2 "hard-stop" computer alerts that prevented prescribing metformin to patients with renal dysfunction and in critical care or postoperative units; and 2 "soft" alerts that fired when no serum creatinine was available or the patient was in an outpatient surgical unit. Charts were reviewed for the presence of contraindications: renal insufficiency, congestive heart failure, recent myocardial infarction, surgery, or intravenous contrast use within 48 hours of metformin administration. In the preintervention group there were 47 violations compared with 13 violations in the postintervention group (P < .001). The greatest improvement was in surgical patients (39 violations vs 11, P < .001). Computer alerts at order entry were effective in decreasing the inappropriate prescribing of metformin in an inpatient setting.

Metformin-Associated Exacerbation of Chronic Pancreatitis: A Possible Adverse Drug-Disease Interaction

Objective: To report a case of metformin-associated exacerbation of chronic pancreatitis and examine this possible drug-disease interaction. Case Summary: A 59-year-old woman with chronic pancreatitis (CP) experienced a severe exacerbation of her characteristic chronic abdominal pain 3 weeks after initiation and titration of metformin therapy; the exacerbation resolved upon discontinuation of metformin. The patient presented to the emergency department experiencing nausea and severe right upper quadrant abdominal pain with radiation to the right flank. Persistent abdominal pain, which had been a primary feature of CP, was previously mild and easily controlled with oral analgesics. Laboratory studies ruled out acute pancreatitis and were significant only for elevated glucose (168 mg/dL). Subsequently, she was given intravenous pain and nausea medications and discharged to home. The pain and nausea shortly returned and continued for 3 more days, at which point she telephoned her gastroenterologist, who advised that she discontinue metformin because of possible adverse reaction. Within a few days of discontinuing metformin, the nausea resolved and abdominal pain gradually returned to baseline level. Discussion: Metformin is not generally known to cause or exacerbate pancreatitis, although cases of acute pancreatitis associated with metformin therapy have been reported in the literature. No cases involving chronic pancreatitis have been reported. Consequently, metformin's prescribing guidelines do not contain precautions or contraindications for patients with chronic pancreatitis. Use of the Naranjo probability scale for assessment of this case revealed that the adverse drug effect was possible, reflecting the symptomatic resolution upon discontinuation while accounting for the lack of causative certainty, previous conclusive case reports, as well as the presence of possible nondrug causes. Conclusions: To our knowledge, this is the first case describing metformin-associated exacerbation of chronic pancreatitis. Although this occurrence may be rare, cautionary consideration, education, and monitoring should accompany initiation of metformin therapy in select patients with chronic pancreatitis.

Geographic variation in pharmacotherapy decisions for U.S. medicare enrollees with diabetes

ObjectivesPrescription rates for diabetic drugs vary considerably across the United States for Medicare beneficiaries. The goal of this study was to determine if non-clinical factors (patient race, ethnicity, gender, income) are associated with regional variation in pharmacotherapy decisions for diabetic patients enrolled in Medicare. MethodsWe performed a spatially-weighted, linear regression analysis of the entire diabetic population enrolled in Medicare Parts A, B, and D for the years 2006 through 2009. Our outcomes of interest were the percentage of diabetic patients being treated with metformin, a sulfonylurea, a thiazolidinedione, or insulin within a hospital referral region (HRR). ResultsPrescription rates for metformin, sulfonylureas, thiazolidinediones, and insulin varied more than two-fold between hospital referral region. Metformin prescription rates were increased in western states while prescription rates for sulfonylureas and insulins were highest in the South and Midwest. In contrast with these other diabetic drug classes, members of the thiazolidinedione drug class were prescribed more frequently in the Central United States (Great Plains, Colorado Rockies, Northern Texas, Oklahoma). Prescription rates for each drug class were increased in hospital referral regions with a lower household income. Referral regions with larger African American populations were associated with higher prescription rates for insulin (p<0.001) and lower prescription rates for metformin (p<0.001). Gender and Hispanic ethnicity were not associated with regional variation in prescription rates for the four major diabetic drug classes. ConclusionsGeographic differences exist in the management of type 2 diabetes for Medicare enrollees. Prescription patterns were associated with household income and African American race. Further studies are necessary to identify local, unidentified factors that might be influencing provider management styles.

Effects of metformin and sulfonylureas on overall and colorectal cancer-specific mortality.

2599 Background: Preclinical studies have suggested a role for metformin in the treatment of colorectal cancer (CRC). Associations between metformin versus sulfonylurea exposure and mortality (all-cause and colorectal cancer specific) are assessed in this population-based study of patients with a diagnosis of stage I-IV CRC. Methods: National Cancer Registry Ireland records were linked to prescription claims data and used to identify a cohort of patients with incident TNM stage I-IV CRC diagnosed 2001-2006. From this cohort, 2 patient groups were identified and compared for outcomes - those who received a prescription for metformin +/- a sulfonylurea (MET) or a prescription for sulfonylurea alone (SUL) in the 90 days pre CRC diagnosis. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) were estimated using Cox proportional hazards models adjusted for age, sex, stage, grade, site, comorbidities, year of diagnosis, and insulin, aspirin or statin exposure. Analyses were repeated stratifying by stage and site. Results: 5,617 patients with stage I-IV CRC were identified, of whom 369 received a prescription for metformin or a sulfonylurea in the 90 days pre diagnosis (median follow-up 1.6 years; MET: n=257; SUL: n=112). In adjusted analyses metformin exposure was associated with a 28% lower risk of all-cause mortality relative to sulfonylurea exposure (HR 0.72, 95% CI 0.53-0.98) and a non-significant 24% reduction in CRC-specific mortality (HR 0.76, 95% CI 0.52-1.13). In analyses stratified by site, in colon cancer, metformin exposure was associated with a significant one-third reduction in all-cause mortality (HR 0.66, 95% CI 0.46-0.95) and a non-significant reduction in site-specific mortality (HR 0.64, 95% CI 0.40-1.02). No mortality benefit was observed for rectal cancer. The association between metformin exposure and reduced mortality was strongest for stage I/II disease (all-cause mortality: HR 0.56, 95% CI 0.32-0.98; CRC-specific mortality: HR 0.48, 95% CI 0.21-1.11). Conclusions: Pre-diagnosis metformin exposure in CRC patients was associated with a significant reduction in mortality relative to sulfonylurea exposure. This benefit was greatest in patients with colon cancer and early stage disease.