Oral Antihyperglycemics Research Articles

387-P: High Incidences of Level 3 Severe Hypoglycemia Reported by T2DM Secretagogue-Users (iNPHORM, USA)

In the US, >90% of people with T2DM on oral antihyperglycemics use secretagogues. The present analysis is the first to quantify the real-world, US frequency of Level 3 severe hypoglycaemia (SH) in this population. Longitudinal, prospective data were leveraged from the iNPHORM study. Adults (≥18 years old) with secretagogue-treated T2DM (not on insulin) were recruited from a US-wide, probability-based internet panel. Data on participant characteristics and Level 3 SH occurrence were captured across a screener, baseline and 12 monthly follow-ups. Multivariable negative binomial regression with cluster bootstrapping for repeated measures modelled the annualized rate of SH for individuals completing ≥1 follow-up(s). A repeated lasso regression ‘voting’ procedure selected all risk factors. Multiple imputation addressed missingness. Of the 353 respondents (male: 51.1%; age: 54.6 [SD: 13.2] years; diabetes duration: 10 [IQR: 12] years; retention rate: 84.4%), the incidence proportion of SH over follow-up was 21.8 (95% CI: 17.8-26.3)%, and the rate was 3.8 (95% CI: 2.5-5.7) events per person-year. Our final model included age, continuous/flash glucose monitoring use, corticosteroid use, number of healthcare visits, fear of hypoglycemia, number of past-year SH requiring hospital care, retinopathy, and other diabetes complications. The rate of annualized Level 3 SH statistically increased with younger age, more frequent healthcare visits, greater fear of hypoglycemia, higher number of past-year healthcare-related SH, and presence of retinopathy. Our results indicate disturbingly high incidences of Level 3 SH among secretagogue users. Whenever logical and feasible, clinicians should prioritize one of the many other available antihyperglycemics that confer little to no hypoglycemia risk. Else, other hypoglycemia prevention strategies—risk-tailored to this ubiquitous T2DM population—are urgently warranted. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

Impact of treatment modalities on quality of life and depression in type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is a chronic disease with numerous complications that increase mortality and reduce the quality of life (QoL). The current study compares QoL in T2DM patients treated with insulin to those treated with oral antihyperglycemics (OAHs), as well as the frequency and severity of depression in patients. This prospective cross-sectional study included 200 patients with insulin or OAHs. Triglycerides, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol levels were measured. The Beck Depression Inventory and the SF-36 Quality of Life Questionnaire were used to assess depression symptoms and QoL in response to different treatment modalities. Insulin-treated patients have a longer duration of illness, higher preprandial glycemic levels, lower scores in three of four dimensions of the SF-36 physical component, and a lower score in the SF-36 psychological component's emotional role dimension. Patients on insulin have milder depression symptoms than those with OAHs. Depression symptoms, according to the findings, worsen QoL and glycemic control in insulin-treated patients. According to these findings, any treatment modality's success in T2DM patients primarily depends on psychological support and preventive measures that promote and maintain mental health.

Implementation of the appointment-based model in community pharmacies: An analysis of refills and adherence

BackgroundTraditionally, much of community pharmacy practice relies on patients to request their own medication refills. These refills are often not aligned, which has been shown to decrease adherence and workflow efficiencies. The appointment-based model (ABM) is designed to proactively synchronize refills and schedule patient-pharmacist appointments. ObjectivesTo describe the characteristics of patients enrolled in the ABM; and to compare the number of distinct refill dates, number of refills, and adherence for antihypertensives, oral antihyperglycemics, and statins 6-months and 12-months pre-post ABM implementation. MethodsIn September 2017, the ABM was implemented across independent community pharmacies within a pharmacy banner in Ontario, Canada. In December 2018, a convenience sample of three pharmacies was extracted. Demographic and clinical characteristics were collected on program enrollment (index) date for individual patients and their medication fill histories were used to investigate adherence measures including distinct number of refill dates, number of refills, and proportion of days covered. Descriptive statistics were analyzed using StataCorp. ResultsAnalysis of 131 patients (48.9% male; mean age 70.8 years ± 10.5 SD) filled on average 5.1 ± 2.7 medications with 73 (55.7%) experiencing polypharmacy. Patients had a significant reduction in mean number of refill dates (6.8 ± 3.8 SD six-months pre-enrollment, 4.9 ± 3.1 SD six-months post-enrollment, p < 0.0001). Adherence to chronic medications remained high (PDC ≥95%). ConclusionThe ABM was implemented for a cohort of established users, already highly adherent to their chronic medications. Results demonstrate reduced filling complexity and fewer refill dates while also sustaining the high baseline adherence across all chronic medications studied. Future studies should investigate patient perspectives and potential clinical benefits of the ABM.

Preoperative prescriptions and polypharmacy in elective total hip and knee arthroplasty from 2010 to 2017, a descriptive cohort study.

Evaluation of regular medication is an essential part of the preanesthetic consultation. However, even in elective surgical patients, such as those scheduled for total hip (THA) and knee arthroplasty (TKA), this task may be increasingly complex due to increasing age and number of pharmacologically treated comorbidities. Nevertheless, data on prescribed drugs and polypharmacy in elective surgical patients is sparse. Descriptive study in elective unilateral fast-track THA and TKA between 2010 and 2017 based on data fromthe Centre for fast-track Hip and Knee Replacement Database. Nationwide information on dispensed prescriptions up to 3 months preoperatively was acquired from the Danish National Database of Reimbursed Prescriptions. Drugs were divided into individual subgroups according to the fourth Anatomical Therapeutic Chemical level (ATC4). Primary outcome was changes in the median number of prescribed drugs/year. Secondarily, we investigated the fraction of patients with polypharmacy (≥5 individual ATC4-subgroups), severe polypharmacy (≥10) and specific drugs of relevance at the preanesthetic evaluation. Of 36,934 procedures in 32,515 patients with a median age of 69 years, we found a median of 3 ATC4-subgroups with no time-related changes regardless of year of surgery but increasing in patients ≥65 years (median: 3 [IQR: 2-4]) versus < 65 years (2 [IQR 1-3]; p< .001). In total, 35.1% and 4.2% had polypharmacy or severe polypharmacy. There was a significant declining trend in severe polypharmacy from 2010 to 2017 (p= .003). Drugs of anesthetic relevance were used by 41.1% of all patients, most often ANG-II or ACE inhibitors and betablockers, which were used by 28.0% and 15.7%. Oral antihyperglycemics was used by 7.8% and 2.0% used insulin. Only 4.0% and 2.1% of patients used vitamin-K antagonists and direct oral anticoagulants, respectively. MAO-inhibitors/Lithium salts were used by 0.3%. The combination of ANG-II/ACE inhibitors, a diuretic and NSAID ("triple whammy") was present in 4.3% of all patients. Patients scheduled for elective THA and TKA used a median of 3 prescribed drugs. However, 1/3 of patients qualified as having polypharmacy and 41% used drugs requiring anesthetic consideration when planning for surgery.

Persistently High Glycated Hemoglobin in a Subgroup of Type 2 Diabetic Patients Who Failed Usual Oral Antihyperglycemics and Insulin in C&amp;#244;te d’Ivoire

Persistently High Glycated Hemoglobin in a Subgroup of Type 2 Diabetic Patients Who Failed Usual Oral Antihyperglycemics and Insulin in C&amp;#244;te d’Ivoire

OR03-1 Achievement of HbA1c &amp;lt;6.5% without weight gain and hypoglycemia in people with type 2 diabetes treated with tirzepatide across the phase 3 SURPASS program

Abstract Introduction Tirzepatide, the novel dual GIP/GLP-1 receptor agonist for the treatment of type 2 diabetes, has been shown to reduce HbA1c and weight, with more patients achieving HbA1c ≤6.5%, compared to placebo and active comparators in the phase 3 SURPASS 1-5 studies. This analysis compared the percentage of patients treated with tirzepatide achieving a composite endpoint of HbA1c &amp;lt;6.5% without weight gain and hypoglycemia in these studies. Methods We compared the proportion of participants achieving the composite endpoint between the tirzepatide (5, 10, or 15 mg) and respective comparator groups while patients were on treatment and without rescue medication. Missing data was imputed based on observed data in the same treatment arm from subjects who had their efficacy measure at the endpoint visit assessed after early discontinuation of study drug. End of treatment HbA1c and weight were evaluated at week 40 (SURPASS-1, 2, 5) and week 52 (SURPASS-3, 4). Weight gain was defined as a change from baseline in weight &amp;lt;0.1 kg. Hypoglycemia included blood glucose level &amp;lt;54 mg/dL with symptoms of hypoglycemia or severe hypoglycemia. Results In SURPASS-1, 2, 3, 4, and 5 significantly more patients treated with tirzepatide achieved the composite endpoint compared to placebo or comparator (P≤0.002). As a monotherapy in SURPASS-1, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (75%, 78%, 83%, and 5%, respectively; all P&amp;lt;0.001). As add-on to metformin in SURPASS-2, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than semaglutide (67%, 77%, 83%, and 59%, respectively; P=0.002, P&amp;lt;0.001, P&amp;lt;0.001, respectively). When compared to basal insulin in SURPASS-3, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin degludec (63%, 76%, 82%, and 13%, respectively; all P&amp;lt;0.001). When added to 1-3 oral antihyperglycemics in SURPASS-4, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than insulin glargine (56%, 68%, 75%, and 10%, respectively; all P&amp;lt;0.001). As an add-on to basal insulin in SURPASS-5, significantly more patients treated with tirzepatide 5mg, 10mg, 15mg achieved the composite endpoint than placebo (63%, 70%, 76%, and 8% respectively; all P&amp;lt;0.001). Conclusions Significantly more patients treated with tirzepatide achieved a composite endpoint of HbA1c &amp;lt;6.5% without weight gain or hypoglycemia than those treated with placebo, semaglutide, insulin degludec, or insulin glargine in the phase 3 SURPASS program. Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.

Predicting the Need for Basal-Bolus Insulin in Hospitalized Patients With Hyperglycemia: Is Sliding Scale Sometimes the Answer?

Uncontrolled blood glucose (BG) is associated with increased risk of infection, complications, and mortality in hospitalized patients. American Diabetes Association guidelines currently recommend basal insulin for all hospitalized, non-critically ill patients requiring insulin and state that “use of only a sliding scale insulin regimen in the inpatient hospital setting is strongly discouraged”. In practice, however, sliding scale only is used not infrequently. Here, we challenge the recommendation for universal basal insulin use and leverage machine learning to predict which inpatients would indeed benefit from basal insulin at time of admission.Querying inpatient electronic health record data for hospitalizations between 2008–2020, we identified a cohort of 16,868 unique patients who achieved a day of “good control”, defined as ≥ 3 BGs that were within 100–180 mg/dL without any values outside that range. Inclusion criteria were adult inpatients receiving subcutaneous insulin with BG of 100-180mg/dL on one calendar day. If patients had more than one “good day”, the first day of their most recent hospitalization was chosen. We excluded patients ordered for insulin pumps, insulin infusion, any insulin type that is rarely used (ordered < 25 times), TPN or PPN, or tube feeds. We also excluded patients with missing weights.We aimed to predict which patients would require > 6 units of insulin. We chose this threshold clinically, as patients with a total daily dose (TDD) of insulin < 6 units could reasonably be managed on sliding scale insulin alone. Using the threshold of 6 units, we used an ensemble machine learning method, called SuperLearner, to model a binary classification for high vs. low insulin users. Features included in the algorithm were collected prior to prediction time, including weight, height, age, sex, race, insurance status, A1c categories (normal, high, panic high, and missing), creatinine, diet, steroid use in prior 48 hours, admission BG, summary statistics of BG, numerous counts of relevant lab values in quantiles, history of basal insulin use, and counts of major diagnosis code groups. Prior insulin doses were not considered to better simulate admission insulin dosing.Compared to using only weight in the model, with an area under the receiver operating curve (AUROC) of 0.59, our machine learning algorithm showed excellent predictive ability, with an AUROC of 0.85 (95% CI: 0.84 - 0.87) and area under the precision recall curve (AUPRC) of .65 (95% CI: 0.64 - 0.68) vs 0.29 with the weight-only model. Although it will need to be validated prospectively, our algorithm could be used to emphasize basal-bolus insulin on admission in patients predicted to require more insulin, whereas those predicted to require less could be started on sliding scale insulin or considered for oral anti-hyperglycemics.

Unilateral hemichorea and hemiballismus: Rare complications of non-ketotic hyperglycemia

Hemichorea-hemiballismus is an extremely rare and dramatic complication of non-ketotic hyperglycemia in patients with uncontrolled diabetes mellitus. Here, we present the case of a 65-year-old male, known hypertensive, diabetic with the left eye retinopathy who presented with the chief complaints of sudden onset hemichorea and hemiballismus on the right upper and lower limbs. Magnetic resonance imaging brain reported T1 hyperintense and T2 isointense/hypointense signal in the left putamen with no restricted diffusion – these signal changes. He was started on oral antihyperglycemics and a combination of tetrabenazine, clonazepam, and haloperidol. Mild resolution of symptoms was seen and the patient is on follow-up with advice to control sugar through diet and regular sugar monitoring.

Evaluation of Dipeptidyl Peptidase-IV Inhibitor Use in the Inpatient Setting

Background: The American Diabetes Association recommends discontinuing non-insulin antihyperglycemic therapy during hospitalization and utilizing a basal insulin-containing regimen for patients with type 2 diabetes mellitus (T2DM). Limited research is available on the role of dipeptidyl peptidase-IV (DPP-IV) inhibitors in an inpatient real-world patient population. Objective: To determine the efficacy of DPP-IV inhibitor therapy in hospitalized patients with T2DM. Methods: Adult patients with T2DM and received at least one dose of DPP-IV inhibitor during hospitalization were included. The primary outcome was to determine the mean daily blood glucose (BG) readings in the overall patient population. Secondary outcomes included comparing study groups and evaluating mean daily blood glucose, hospital length of stay (LOS) and incidence of hypoglycemia. Results: One hundred and ninety-two patients were identified: 39 patients (20.3%) received DPP-IV inhibitor monotherapy, 104 (54.2%) received DPP-IV inhibitor plus oral antihyperglycemics and 49 (25.5%) received DPP-IV inhibitor plus insulin. Mean daily BG in the entire study population was 158.7 mg/dL (131-187.5). Mean daily BG was significantly different between groups (117 mg/dL [103.5-132.3] vs. 160.7 mg/dL [133-181.1] vs. 179.4 mg/dL [153.8-216.6]; (P < 0.001). Hypoglycemic events were higher in the DPP-IV inhibitor plus insulin group (2.6% vs. 3.8% vs. 16.3%; P = 0.008). There were no significant differences in hospital LOS (2 days [1-4] vs. 3 days [1-5] vs. 4 days [2-6.5]; P = 0.051). Conclusions: Inpatient DPP-IV inhibitor use was associated with mean daily BG within goal range. Administering DPP-IV inhibitors in the inpatient setting should be considered in hospitalized patients with controlled T2DM.

A Systematic Review on Synthetic Drugs and Phytopharmaceuticals Used to Manage Diabetes.

Diabetes is a multifactorial disease and a major cause for many microvascular and macrovascular complications. The disease will ultimately lead to high rate mortality if it is not managed properly. Treatment of diabetes without any side effects has always remained a major challenge for health care practitioners. The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed. Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was sorted in terms of various approaches that are used for the treatment of diabetes. More than 170 papers including both research and review articles, were included in this review in order to produce a comprehensive and easily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in the management of diabetes is also highlighted. Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination, can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics are a more holistic therapy due to their natural origin and traditional use.

A Cross-Sectional Study of Overtreatment and Deintensification of Antidiabetic and Antihypertensive Medications in Diabetes Mellitus: The TEMD Overtreatment Study.

IntroductionTargeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians’ attitudes to deintensify or intensify treatment.MethodsData from older adults (≥ 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c < 6.5% plus the use of ≥ 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) < 120 mmHg or diastolic BP (DBP) < 65 mmHg plus the use of ≥ 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s).ResultsThe rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. In the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2–3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0–3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14–3.04). There was no independent association of BP undertreatment to the study confounders. The deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP.ConclusionsThe results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM.Trial RegistrationClinicalTrials.gov identifier, NCT 03455101.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00779-0) contains supplementary material, which is available to authorized users.

1031 Social and Medical Determinants of NASH versus NAFLD Using Liver Histology: A Single Center Experience

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is pandemic across the world and has a wide spectrum of presentations. Both NAFLD and its most severe histopathologic subtype, non-alcoholic steatohepatitis (NASH), can progress to cirrhosis, making early diagnosis pivotal. Liver histology is critical for the diagnosis of NASH, however little is known about the association of social and medical factors with its histologic features. We are conducting a retrospective analysis of a large single center database of over 2000 patients with fatty liver disease proven by biopsy. Here we focus on one year of data collected at our institution. METHODS: We reviewed 653 liver biopsies from a one-year period at Methodist Liver Institute to identify subjects with NAFLD and NASH based on the NAFLD Activity Score (NAS). NASH was defined as NAS score = &gt;3. Patients under the age of 18, documented significant alcohol use, and without steatosis were excluded. We then collected data on demographics (age, race, insurance, and median income), comorbid disease (diabetes mellitus, hypertension, hyperlipidemia, metabolic syndrome), and medication use (antihypertensives, oral antihyperglycemics, insulin, statins, opioids), and used univariate statistical analysis to compare subjects with and without NASH. RESULTS: Of 253 biopsies included, 118 had steatosis without NASH and 145 had steatosis with NASH. Subjects with NASH were significantly younger, and more likely to be of Caucasian race than African American race, have Medicaid than commercial insurance, and have diabetes mellitus with use of oral antihyperglycemics. There was no significant difference between NASH and no NASH groups with regards to BMI, hypertension, hyperlipidemia, metabolic syndrome, or use of antihypertensives, statins, insulin, or opioids (Table 1). CONCLUSION: Though histologic confirmation is the gold standard to distinguish NAFLD from NASH, there is a lack of data establishing prognostic factors that may predict the degree of fibrosis. In our analysis having diabetes mellitus or Medicaid instead of commercial insurance correlated with more severe histopathologic disease, suggesting that more aggressive screening and treatment should be promoted in this population. There was no significant difference in socioeconomic factors such as median income or metabolic syndrome. Our study was limited by small size, and data collection is ongoing to determine other factors that may contribute to worsening fibrosis and validate or refute these early findings.

The Effect of Age and Comorbidities on the Association Between the Medicare STAR Oral Antihyperglycemic Adherence Metric and Glycemic Control.

The Medicare STAR program for Medicare Advantage Plans that include drug benefits provides monetary incentives for health plans to achieve good adherence to oral antihyperglycemic (OAH) agents but does not account for differential case mix that could affect the ability of health plans to achieve the required quality metrics. To determine whether OAH adherence varies by age and comorbidities among patients aged 65 years or older and the extent to which adherence affects glycemic control across age and comorbidity strata. We studied 54,480 patients with diabetes aged > 65 years from the Colorado, Northwest, and Northern California regions of Kaiser Permanente who received OAH agents but not insulin in 2010. We calculated adherence using the proportion of days covered (PDC) method. Per the STAR program, hemoglobin A1c < 8% defined good glycemic control. We also defined poor control as A1c > 9%. We used modified Poisson regression to identify predictors of adherence and to determine its effects on A1c across age and comorbidity strata, adjusting for sociodemographics and medication-related variables. The risk of being adherent to OAH declined moderately with an increasing number of comorbidities (risk ratio [RR] = 0.99, 95% CI = 0.98-1.00 for 1 comorbidity and RR = 0.90, 95% CI = 0.88-0.91 for 4 or more comorbidities). Adherence to OAH agents was associated with a 0%-3% increased risk of A1c < 8% across age and comorbidity categories, as well as a large decreased risk (RR = 0.55-0.73) of A1c > 9% for patients aged < 80 years or with < 3 comorbidities. Among patients with diabetes aged > 65 years, having multiple comorbidities affects adherence. Adherence reduces the risk of poor A1c control among patients aged 65-79 years or with 2 or fewer comorbidities. Our results suggest that health plan case mix minimally influenced the Medicare STAR OAH adherence metric, but it may affect glycemic control quality measures, especially if a HEDIS-like measure of poor control were adopted. This study was supported by grant number 1R21DK103146-01A1 from the National Institute of Diabetes and Digestive and Kidney Disorders. Nichols currently receives grant funding from Boehringer-Ingelheim, Sanofi, Amarin Pharma, and Janssen Pharmaceuticals for other unrelated research projects. The other authors declare no conflicts of interest. This study was presented at the American Diabetes Association's 77th Scientific Sessions; June 9-13, 2017; San Diego, CA.

Safety and efficacy assessment of a GLP-1 mimetic: insulin glargine combination for treatment of feline diabetes mellitus

A commonly used therapeutic strategy for type 2 diabetes mellitus (DM) in humans involves the use of synthetic incretin hormone-based therapies including exenatide, a glucagon-like pepetide-1 hormone agonist. Glucagon-like pepetide-1 agonists can be used alone or as an ancillary therapy with other agents, including insulin and oral antihyperglycemics. Little is known about the role of these therapies for DM in cats. Therefore, the primary objective of this study was to evaluate the safety and efficacy of short-acting exenatide combined with insulin, as compared to placebo and insulin for the treatment of DM in cats. Treatment with exenatide was well tolerated; only 2 cats developed side effects requiring dose reduction. Two cats (25%) went into diabetic remission while receiving exenatide and insulin, whereas remission was not reported during placebo treatment. The average change in the daily exogenous insulin dose was significant (β = −0.56 U/kg, 95% confidence interval, −0.96 to −0.15, P = 0.007), and the dose of insulin administered was lower during exenatide treatment. The average weight loss experienced on exenatide was significantly higher than on placebo (β = 0.65 kg, 95% confidence interval, 0.09–1.21, P = 0.02). There was no significant difference in any of the hormone concentrations evaluated for cats on exenatide vs placebo treatments. Overall, the treatment of diabetic cats with insulin and a fixed dose of exenatide was found to be safe. The weight loss and decreased exogenous insulin requirement experienced with exenatide treatment could be a significant benefit for overweight diabetic cats and warrants further evaluation.

Magnitude and Pattern of Placebo Response in Clinical Trials of Oral Antihyperglycemic Agents: Data From the U.S. Food and Drug Administration, 1999-2015.

To evaluate the magnitude of placebo response and treatment response patterns in clinical trials of investigational oral antihyperglycemics over time. We examined the U.S. Food and Drug Administration medical and statistical reviews for 19 oral antihyperglycemic agents (23,438 patients, 50 trials, and 96 treatment arms) approved between 1999 and 2015. Placebo and medication treatment response (HbA1c reduction) and effect sizes were examined over time (year of approval). Exclusively placebo-controlled and augmented/adjunctive placebo-controlled trials were analyzed separately, and differences were compared. Potential effects of trial and patient characteristics were explored. In more recent trials, augmented placebo-controlled arms reduced HbA1c by 0.2% on average and more frequently lowered HbA1c from baseline compared with exclusively placebo-controlled arms (63 vs. 18%; χ2 = 9.93; P = 0.002). In exclusively placebo-controlled trials, placebo response increased significantly over time (β = 0.035; R2 = 0.31; P = 0.0013), reaching ∼0% average change in HbA1c, whereas drug response also increased significantly (β = 0.017; R2 = 0.076; P = 0.0498). In augmented placebo-controlled trials, placebo response (β = 0.33; R2 = 0.407; P < 0.001) showed the same pattern, whereas the growth in drug response was not significant (R2 = 0.031; P = 0.207). Placebo response in both groups increased by 0.5% HbA1c reduction over time, whereas effect sizes remained stable with high success rates (100%; 96 out of 96). Drug response and effect size were not significantly predicted by patient or trial characteristics, but follow-up analysis suggested an inverse relationship of placebo baseline HbA1c with placebo response. Remarkably, placebo-treated patients with diabetes commonly experienced reduction in HbA1c, more markedly in augmented compared with exclusively placebo-controlled treatment arms. Placebo response increased significantly over time without impacting efficacy outcomes. Nonpharmacologic effects measured in the placebo response appear stronger when used with active medication than when implemented in isolation and may be related to the level of HbA1c at baseline.

Type 2 Diabetes Mellitus, Oral Antihyperglycemics, Insulin Use, and Outcomes Among Men Receiving Radiation Therapy for Prostate Cancer

Type 2 Diabetes Mellitus, Oral Antihyperglycemics, Insulin Use, and Outcomes Among Men Receiving Radiation Therapy for Prostate Cancer

Health care system-level factors associated with performance on Medicare STAR adherence metrics in a large, integrated delivery system.

Background:The Centers for Medicare and Medicaid Services provide significant incentives to health plans that score well on Medicare STAR metrics for cardiovascular disease risk factor medication adherence. Information on modifiable health system-level predictors of adherence can help clinicians and health plans develop strategies for improving Medicare STAR scores, and potentially improve cardiovascular disease outcomes.Objective:To examine the association of Medicare STAR adherence metrics with system-level factors.Research Design:A cross-sectional study.Subjects:A total of 129,040 diabetes patients aged 65 years and above in 2010 from 3 Kaiser Permanente regions.Measures:Adherence to antihypertensive, antihyperlipidemic, and oral antihyperglycemic medications in 2010, defined by Medicare STAR as the proportion of days covered ≥80%.Results:After controlling for individual-level factors, the strongest predictor of achieving STAR-defined medication adherence was a mean prescribed medication days’ supply of >90 days (RR=1.61 for antihypertensives, oral antihyperglycemics, and statins; all P<0.001). Using mail order pharmacy to fill medications >50% of the time was independently associated with better adherence with these medications (RR=1.07, 1.06, 1.07; P<0.001); mail order use had an increased positive association among black and Hispanic patients. Medication copayments ≤$10 for 30 days’ supply (RR=1.02, 1.02, 1.02; P<0.01) and annual individual out-of-pocket maximums ≤$2000 (RR=1.02, 1.01, 1.02; P<0.01) were also significantly associated with higher adherence for all 3 therapeutic groupings.Conclusions:Greater medication days’ supply and mail order pharmacy use, and lower copayments and out-of-pocket maximums, are associated with better Medicare STAR adherence. Initiatives to improve adherence should focus on modifiable health system-level barriers to obtaining evidence-based medications.

Type-2 Diabetes and Kidney Stones: Impact of Diabetes Medications and Glycemic Control

To evaluate the impact of diabetic medications and glycemic control on the urine pH, 24-hour urine stone risk profile, and stone composition. We retrospectively reviewed our database searching for type-2 diabetic patients with kidney stones from July 2002 to January 2013. Patients were divided in 2 groups according to their diabetic medications: insulin vs oral antihyperglycemics. Patients were compared based on their urine collections and stone composition. A linear regression was done to assess which variables could predict a low urine pH. In a subgroup analysis, patients on thiazolidinediones (ie, pioglitazone) were compared with patients on other oral antihyperglycemics. We analyzed 1831 type-2 diabetic patients with stone disease; 375 (20.5%) were included in the insulin group and 1456 (79.5%) in the antihyperglycemics group. Linear regression revealed male gender (P = .011) and insulin therapy (P <.001) as protective factors of low urine pH, whereas HbA1c level (P <.001) was inversely related to the urine pH (odds ratio, -0.066; 95% confidence interval, -0.096 to -0.036; P <.001). There were no significant differences in other 24-h urine stone risk parameters or stone composition between the groups. There were also no significant differences in the subgroup analysis. Urine pH is inversely related to HbA1c level. Insulin therapy is associated with higher urine pH than oral antihyperglycemic agents despite higher HbA1c suggesting that insulin may modify urine pH independent of glycemic control.

Management and Control of Patients with Type 2 Diabetes Mellitus in Lebanon Results from the International Diabetes Management Practices Study ( IDMPS )

The IDMPS is a study to identify changes in diabetes treatment practice in several developing countries. This paper focuses on diabetes management and compliance with guidelines in a Middle Eastern country like Lebanon. The cross-sectional data from the 2006 wave of two weeks duration on the Lebanese population along with the longitudinal data of a 9-month follow-up study were collected. A large proportion of Lebanese patients were not adequately controlled or followed up. A slight proportion was managed by diet and exercise alone while most patients were on two or more oral anti-hyperglycemics. Metformin was the most common monotherapy followed by sulfonylureas. 22.6% of Lebanese patients were on insulin, most commonly basal insulin alone followed by premix insulin alone. Blood glucose self-monitoring was more frequently done by insulinized patients and was associated with better glycemic control. Glycemic control was reached in 29.6% of type 2 patients (HbA1c < 7%) with poorest outcome for patients on insulin and was more frequently achieved in patients who had more frequent monitoring of HbA1c levels. For a proper assessment of diabetic control, maintaining adherence to international guidelines needs to be evaluated. Promoting patient education, improving physician knowledge with better implementation of guidelines is recommended.

Design of the liraglutide effect and action in diabetes: Evaluation of cardiovascular outcome results (LEADER) trial

Diabetes is a multisystem disorder associated with a nearly twofold excess risk for a broad range of adverse cardiovascular outcomes including coronary heart disease, stroke, and cardiovascular death. Liraglutide is a human glucagon-like peptide receptor analog approved for use in patients with type 2 diabetes mellitus (T2DM). To formally assess the cardiovascular safety of liraglutide, the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial was commenced in 2010. LEADER is a phase 3B, multicenter, international, randomized, double-blind, placebo-controlled clinical trial with long-term follow-up. Patients with T2DM at high risk for cardiovascular disease (CVD) who were either drug naive or treated with oral antihyperglycemic agents or selected insulin regimens (human NPH, long-acting analog, or premixed) alone or in combination with oral antihyperglycemics were eligible for inclusion. Randomized patients are being followed for up to 5 years. The primary end point is the time from randomization to a composite outcome consisting of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. LEADER commenced in September 2010, and enrollment concluded in April 2012. There were 9,340 patients enrolled at 410 sites in 32 countries. The mean age of patients was 64.3 ± 7.2 years, 64.3% were men, and mean body mass index was 32.5 ± 6.3 kg/m2. There were 7,592 (81.3%) patients with prior CVD and 1,748 (18.7%) who were high risk but without prior CVD. It is expected that LEADER will provide conclusive data regarding the cardiovascular safety of liraglutide relative to the current standard of usual care for a global population of patients with T2DM.