Type 2 Diabetes Medications Research Articles

General practitioner and nurse experiences of type 2 diabetes management and prescribing in primary care: a qualitative review following the introduction of funded SGLT2i/GLP1RA medications in Aotearoa New Zealand.

To explore the views of general practitioners (GPs) and nurses on type 2 diabetes (T2D) management, including the use of recently funded T2D medications in New Zealand (NZ) and their perceived barriers to providing optimal care. T2D is a significant health concern in NZ, particularly among Māori and Pacific adults. Characterised by prolonged hyperglycaemia, T2D is generally a progressive condition requiring long-term care. Semi-structured interviews were conducted between July and December 2022 with 21 primary care clinicians (10 GPs and 11 nurses/nurse prescribers) from nine different general practice clinics across the Auckland and Waikato regions of NZ. Framework analysis was conducted to identify common themes in clinicians' perceptions and experiences with T2D management. Three themes were identified: health-system factors, new medications, and solution-based approaches. Lack of clinician time, healthcare funding, staff shortages, and burn-out were identified as barriers to T2D management under health-system factors. The two newly funded medications, empagliflozin and dulaglutide, were deemed to be a positive change for T2D care in that they improved patient satisfaction and clinical outcomes, but several clinicians were hesitant to prescribe these medications. Participants suggested that additional education and specialist diabetes support would be helpful to inform optimal medication prescribing and that better use of a multi-disciplinary team (clinical and support staff) could support T2D care by reducing workload, addressing cultural gaps in healthcare delivery, and reducing burnout. An improved primary care work environment, including appropriate professional development to support prescribing of new medications and the value of collaboration with a non-regulated workforce, may be required to facilitate optimal T2D management in primary care. Future research should focus on interventions to increase support for both clinical teams and patients while adopting a culturally appropriate approach to increase patient satisfaction and improve health outcomes.

Patient Out-of-Pocket Costs for Type 2 Diabetes Medications When Aging Into Medicare

For people with type 2 diabetes (T2D), out-of-pocket medication costs may influence medication choice, adherence, and overall diabetes management and progression. Little is known about how these costs change as insured people enter Medicare at age 65 years, when coinsurance in the coverage gap and catastrophic phases of Part D coverage can be increased greatly by use of insulin and newer, branded medications (eg, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 agonists, and sodium-glucose cotransporter 2 inhibitors). To identify whether reaching age 65 years is associated with T2D medication out-of-pocket costs and utilization. This retrospective cohort study (2012-2020) featuring 7 years of follow-up used prescription drug claims data from the TriNetX Diamond Network. Participants included people in the US with diagnosed T2D, and claims for T2D medications were observed both before and after age 65 years. Data analysis was performed from October 2022 to September 2023. Reaching age 65 years, according to participants' year of birth. The primary outcome was patient out-of-pocket costs for T2D drugs per quarter (inflation adjusted to 2020 dollars). Utilization, measured as binary utilization of specific classes, and the number of claims for mutually exclusive classes and combinations of classes were also examined. All outcomes were examined using regression discontinuity design. In claims data for 129 997 individuals with T2D diagnosed at ages 58 to 72 years (mean [SD] age, 65.50 [2.95] years; 801 235 female [50.9%]), reaching age 65 years was associated with an increase of $23.04 (95% CI, $19.86-$26.22) in mean quarterly out-of-pocket costs for T2D drugs, and an increase of $56.36 (95% CI, $51.48-$61.23) at the 95th percentile of spending, after utilization adjustment. Utilization decreased by 5.3% at age 65 years, from 3.40 claims per quarter (95% CI, 3.38-3.42 claims per quarter) to 3.22 claims per quarter (95% CI, 3.21-3.24 claims per quarter), but a shift in composition of utilization, including increased insulin use, was associated with additional increases in patient costs. In this cohort study of individuals with T2D, the increase in spending upon reaching age 65 years (when most people enroll in Medicare) was associated with patient coinsurance in the coverage gap and catastrophic coverage phases of Medicare Part D. The increased patient cost burden at age 65 years and a modest reduction in overall T2D drug utilization suggest that as people with T2D age into Medicare, there is potentially an increase in nonadherence and diabetes complications.

Polygenic subtype identified in ACCORD trial displays a favorable type 2 diabetes phenotype in the UKBiobank population

IntroductionWe previously identified a genetic subtype (C4) of type 2 diabetes (T2D), benefitting from intensive glycemia treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Here, we characterized the population of patients that met the C4 criteria in the UKBiobank cohort.Research design and methodsUsing our polygenic score (PS), we identified C4 individuals in the UKBiobank and tested C4 status with risk of developing T2D, cardiovascular disease (CVD) outcomes, and differences in T2D medications.ResultsC4 individuals were less likely to develop T2D, were slightly older at T2D diagnosis, had lower HbA1c values, and were less likely to be prescribed T2D medications (P < .05). Genetic variants in MAS1 and IGF2R, major components of the C4 PS, were associated with fewer overall T2D prescriptions.ConclusionWe have confirmed C4 individuals are a lower risk subpopulation of patients with T2D.

Weight loss outcomes with semaglutide based on diabetes severity using the individualized metabolic surgery score

Semaglutide demonstrated inferior weight loss responses in patients with type 2 diabetes (T2D) compared to patients with obesity without T2D. The individualized metabolic surgery (IMS) score was validated to predict T2D remission after bariatric surgery. The parameters of the IMS are HbA1c (<7%), insulin use, T2D medications and T2D duration. We aim to assess weight loss outcomes of semaglutide based on IMS score in patients with obesity and T2D. This is a retrospective multicentered cohort study of patients with T2D and BMI≥ 27kg/m2 taking ≥1mg of semaglutide recruited from January 2020 to December 2022. We excluded patients with a history of bariatric surgery or taking other anti-obesity medications. IMS was calculated at baseline and patients weight change was recorded at baseline, 3, 6, 9 and 12 months. IMS was classified as mild (0-24.9 points), moderate (25-94.9 points), and severe (95-180 points). Analysis was performed based on IMS score quartiles and combination of Mild-Moderate vs Severe categories. We performed mixed linear regression models including age, sex, and baseline weight to assess associations between IMS categories with total body weight loss percentage (TBWL%). We included 297 patients (42% female, mean age 62±12 years) in the analysis. At 12 months, there was a stepwise decrease in weight loss outcomes when comparing patients by IMS quartiles (LS mean TBWL%± SE): 8.8±0.8% vs 6.9±0.8% vs 5.7±0.9% vs 5.0±0.8%. In the mixed linear model, patients in the mild-moderate category achieved significantly superior weight loss outcomes (LS mean TBWL± SE:-8.3±0.7%) than patients in the severe category (-5.5±0.6%; difference:-2.9, 95% CI:-5.2 to-0.5, p=0.006) at 12 months. There was no significant difference in glycemic improvement regardless of IMS severity at baseline. In our cohort, lower IMS severity was associated with more weight loss in patients with obesity and T2D. Further studies are needed to understand T2D severity and its effect on semaglutide outcomes. Beyond payment to the research staff by Mayo Clinic, this research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies.

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994-2016) and the NHSII (1995-2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81-1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90-1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74-1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48-0.94), current use (HR = 1.01; 95% CI = 0.80-1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95-1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.

FRI638 Glycemic And Cost Outcomes In Hispanic/Latino People With Type 2 Diabetes Initiating Dulaglutide Or Basal Insulin In The US

Abstract Disclosure: M. Hoog: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. J. Maldonado: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. R. Wangia-Dixon: Employee; Self; Optum Inc. Other; Self; Eli Lilly &amp; Company. R. Halpern: Employee; Self; Optum Inc. Other; Self; Eli Lilly &amp; Company. E. Buysman: Employee; Self; Optum Inc. Other; Self; Eli Lilly &amp; Company. G. Gremel: Employee; Self; Optum Inc. Other; Self; Eli Lilly &amp; Company. A. Huang: Employee; Self; Tigermed. Other; Self; Eli Lilly &amp; Company. M. Konig: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. Hispanic/Latino (H/L) adults in the US have a greater prevalence of type 2 diabetes (T2D) and diabetes-related complications compared to non-H/L adults. Optimal glycemic control remains a challenge in H/L adults with T2D, resulting in poor health outcomes and a substantial comorbidity burden. This study compared glycemic and cost outcomes among H/L adults with T2D who initiated treatment with dulaglutide (DU) or basal insulin (BI). This retrospective cohort study used claims data from the Optum Research Database from July 2014 - March 2022 (commercial and Medicare Advantage). H/L patients with ≥1 pharmacy claim for DU or BI during the identification period (IDP), January 01, 2015 - March 31, 2021, were included. Index date was the date of first claim for DU or BI during the IDP and cohorts were assigned based on index date medication. Patients were required to have continuous enrollment during the 6-month baseline and 12-month follow-up periods; ≥1 claim with baseline T2D diagnosis; ≥1 glycated hemoglobin (HbA1c) test result each in the baseline period and 4-12 months after index date; and no injectable T2D medications at baseline. Cohorts were propensity-score matched on demographic and baseline clinical characteristics. Measures of glycemic control included change in HbA1c from baseline to 12-month follow-up, which was modelled using ordinary least squares regression (OLS) on the matched cohorts, and proportion of patients achieving the HbA1c target of &amp;lt;7.0%. Bootstrap sampling with 5,000 samples was used to compare total costs per 1% change in HbA1c between cohorts. The propensity-score matched cohorts comprised of 2,872 patients with 1,436 patients in each cohort (DU and BI). Most demographic and baseline characteristics were balanced between the cohorts except for age, income, office visit counts, and medical costs. Mean [standard deviation (SD)] age in the DU and BI cohorts was 59.8 [12.8] and 61.4 [12.9] years, respectively. About half of the matched population was male (DU: 54.3%; BI: 51.4%). At 12 months, the mean change from baseline in HbA1c was significantly greater in the DU cohort than BI (DU: -1.4% [1.9]; BI: -0.9% [2.1]; p&amp;lt;0.001) and the total cost per 1% change in HbA1c was significantly lower in the DU cohort than BI (DU: $13,768; BI: $19,128; p&amp;lt;0.001). The proportion of patients achieving HbA1c &amp;lt;7.0% at 12 months was significantly higher among patients initiating DU than BI (DU: 37.9%; BI: 22.1%; p&amp;lt;0. 001). Results from OLS showed that the DU cohort had a larger decrease in HbA1c compared to BI (estimate: -0.57; p&amp;lt;0.001). Patients initiating DU had twice the odds of achieving HbA1c &amp;lt;7.0% compared to BI (odds ratio: 2.19; p&amp;lt;0.001). DU demonstrated better glycemic outcomes and lower costs per 1% HbA1c reduction among H/L adults with T2D compared with those initiating BI. DU may be an effective therapeutic option for this vulnerable population and may help with achieving improved T2D outcomes. Presentation: Friday, June 16, 2023

Association of GLP-1 Receptor Agonists with Chronic Obstructive Pulmonary Disease Exacerbations among Patients with Type 2 Diabetes.

Rationale: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) have worse clinical outcomes compared with patients without metabolic dysregulation. GLP-1 (glucagon-like peptide 1) receptor agonists (GLP-1RAs) reduce asthma exacerbation risk and improve FVC in patients with COPD. Objectives: To determine whether GLP-1RA use is associated with reduced COPD exacerbation rates, and severe and moderate exacerbation risk, compared with other T2D therapies. Methods: A retrospective, observational, electronic health records-based study was conducted using an active comparator, new-user design of 1,642 patients with COPD in a U.S. health system from 2012 to 2022. The COPD cohort was identified using a previously validated machine learning algorithm that includes a natural language processing tool. Exposures were defined as prescriptions for GLP-1RAs (reference group), DPP-4 (dipeptidyl peptidase 4) inhibitors (DPP-4is), SGLT2 (sodium-glucose cotransporter 2) inhibitors, or sulfonylureas. Measurements and Main Results: Unadjusted COPD exacerbation counts were lower in GLP-1RA users. Adjusted exacerbation rates were significantly higher in DPP-4i (incidence rate ratio, 1.48 [95% confidence interval, 1.08-2.04]; P = 0.02) and sulfonylurea (incidence rate ratio, 2.09 [95% confidence interval, 1.62-2.69]; P < 0.0001) users compared with GLP-1RA users. GLP-1RA use was also associated with significantly reduced risk of severe exacerbations compared with DPP-4i and sulfonylurea use, and of moderate exacerbations compared with sulfonylurea use. After adjustment for clinical covariates, moderate exacerbation risk was also lower in GLP-1RA users compared with DPP-4i users. No statistically significant difference in exacerbation outcomes was seen between GLP-1RA and SGLT2 inhibitor users. Conclusions: Prospective studies of COPD exacerbations in patients with comorbid T2D are warranted. Additional research may elucidate the mechanisms underlying these observed associations with T2D medications.

The Association between Medicare Annual Wellness Visits and diabetes outcomes among older adults

AbstractThe rising prevalence of diabetes among older adults is an increasing concern in the United States and is expected to nearly triple within the next 40 years. The purpose of this study was to investigate whether the utilization of Medicare Annual Wellness Visits (AWVs) is associated with changes in type 2 diabetes (T2D) outcomes among older adults Medicare beneficiaries. We conducted an observational retrospective cohort study to compare the T2D outcomes between those who attended AWVs and those who did not from 2017 to 2019. The criteria used for this study include having at least two readings (hemoglobin A1c [A1c] levels, glucose levels, and the number of T2D medications), and for the AWV cohort, the AWVs had to occur between those readings. A total of 508 (2%) Medicare beneficiaries fit our selection criteria. Only 154 (30%) of these patients with T2D participated in AWVs. At baseline, the AWV cohort had lower A1c levels and fewer comorbidities than the non‐AWV cohort. No other statistically significant findings were found. These findings indicate that providers did not utilize AWVs on the more complicated patients, who may need it the most.

1359-P: Gaps in the Use of Evidence-Based Diabetes Medications for NASH

Patients with type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH) are at exceedingly high risk of NASH progression to cirrhosis and end-stage liver disease. T2D medications shown to improve histologic features of NASH, such as GLP-1 receptor agonists and pioglitazone, should be considered for use in all patients with T2D and NASH, unless contraindications exist. However, utilization of T2D medications that benefit NASH are poorly understood. Our objective was to address this gap by examining their use in patients with T2D and NASH engaged with Primary and/or Endocrinology care in the Duke University Healthcare System between 1/1/2019 and 1/1/2021. T2D and NASH were defined by ICD-10 codes, E11.xx and K75.81, respectively and 848 patients were included in the analyses. Mean age of our cohort was 60 (SD 12) years, 62% were female (n=525), 13% (n=110) were Black race and 4.7% (n=40) were Hispanic ethnicity. The mean HbA1c was 7.5% (SD 1.5), and the majority followed with Endocrinology (58.5%, n=496) and used insulin (62.4%, n=529). Only 26.3% (n=223) had an appointment with Duke Hepatology during the study period (either new consultation or follow-up visit). The use of evidence-based T2D medications for NASH was low (34.8%, n=295), with only 31.3% (n=265) and 6.5% (n=55) of patients having been prescribed a GLP-1 receptor agonist or pioglitazone during the study period, respectively. Prescriptions of these medications did not significantly vary by race (Black vs. White unadjusted OR 1.08, 95% CI 0.71, 1.64) or Hispanic ethnicity (unadjusted OR, 1.46, 95% CI 0.77, 2.79). In summary, we observed a large gap between recommended and current use of evidence-based medications for NASH in patients with T2D. Use of pioglitazone was particularly low, despite its low cost and longstanding evidence for use in NASH. Future studies should explore reasons for underuse of these evidence-based T2D medications in NASH, and whether this is changing over time with growing evidence supporting their use in NASH. Disclosure A. Alexopoulos: None. A. Parish: None. M. Olsen: None. B. Batch: Advisory Panel; LLENA (AI). C.A. Moylan: Advisory Panel; Boehringer Ingelheim Inc. Research Support; GlaxoSmithKline plc. M.J. Crowley: None. Funding National Institutes of Health (KL2TR002554)

1054-P: A Physician Survey Focusing on Dose Escalation for Type 2 Diabetes Medications

Objectives: T2D medications often require dose escalation to optimize effectiveness. Physician perceptions of treatment characteristics of type 2 diabetes (T2D) medications have previously been examined, but little is known about perceptions of escalation to the optimal dose. This study examined physicians’ perceptions of dose escalation for medications used to treat T2D. Methods: Data on dose escalation and other factors influencing decision-making for T2D treatment were collected via an online survey of US physicians in 2022. Results: The sample included 501 physicians (348 primary care, 153 endocrinologists). Dose escalation was not frequently considered a primary factor keeping patients’ from reaching treatment goals (mentioned as a factor by only 7.6% of the sample) or a barrier to prescribing T2D medication (16.2%). Factors more likely to keep patients from reaching treatment goals included unhealthy diet (86.6%) and medication adherence (77.4%). The most common reasons that physicians reported for escalating dose levels with their patients are presented in Table 1. Conclusions: Although common with T2D treatments, dose escalation was not perceived to be a significant barrier to prescribing medication or attainment of treatment goals. Multiple factors contribute to the decision to escalate a dose. Disclosure K.Boye: Employee; Eli Lilly and Company. J.Jordan: None. R.Malik: Employee; Eli Lilly and Company. R.A.Cyr: None. L.S.Matza: Research Support; Eli Lilly and Company. Funding Eli Lilly and Company

195-LB: Type 2 Diabetes Data Quality in the All of Us Dataset

Data quality significantly impacts the reproducibility and validity of clinical research. The All of Us Research Program aims to collect biomedical data from one million or more participants, with the goal of enabling discoveries and improving targeted management of diseases like type 2 diabetes (T2D). All of Us data include whole genome sequences (WGS), electronic health records (EHRs), device measurements of physical activity, physical measures, and surveys available for analysis on the Researcher Workbench. The program's Spring 2023 curated data release makes All of Us the world's largest, most diverse genomic dataset of its kind available for broad research use, including 413,457 participants among which 60.4% are female, 44.6% are non-white. To ensure maximum utility of this dataset for T2D researchers, we set out to quantify the data quality among participants who have T2D diagnosis codes in their EHRs. We identified the measurements and laboratory tests (hemoglobin A1C, height, weight, body mass index), medications (Insulin and non-insulin), and procedures commonly used in T2D research. We quantified data fitness using five dimensions of quality: completeness, concordance (i.e., agreement), conformance to data standards, plausibility, and temporality. Among 287,012 participants who shared EHRs, 40,093 (14%) had T2D diagnosis codes where the mean age at first diagnosis was 56. Regarding measurements, 68% had A1C, 89% had height, and 70% had weight recorded in their EHR. For plausibility, 99.7% of weights, 99.9% of heights, and 99.3% of BMI were valid, and 97% of heights and weights have high concordance values. For medications, 99.7% of T2D participants had T2D medications, and 47.6% were prescribed after T2D diagnosis. Of these T2D participants, 69% have WGS or array data available. Our analysis shows that the All of Us dataset offers a valuable and high-quality dataset for T2D phenotyping and diagnosis research. Our quality report and code will be available for replication and reuse by researchers with the upcoming release. Disclosure L. Sulieman: None. J. Giannini: None. E. Dede yildirim: None. Y. Ostchega: None. E. Ochsenfaber: None. L. Berman: None. A. Ramirez: n/a.

248-OR: Diabetes Remission after Gastric Bypass Is Characterized by Upregulation of LXR and Antioxidant-Related Pathways in Jejunum

We have previously shown that intestinal adaptation precedes and relates to metabolic improvement in humans after Roux-en-Y gastric bypass surgery (RYGB). Based on this, we hypothesized that persistence of this adaptation at the one-year postoperative timepoint occurs selectively in patients with persistent postoperative metabolic improvement, versus those without Type 2 diabetes (T2D) remission. RNA-seq was used to determine gene expression in jejunum collected before and 12 months (± 1 month) after RYGB. T2D was defined as HbA1c &amp;gt;6.5% or requiring T2D medications prescribed for prior diagnosis of diabetes. Remission was defined as HbA1c &amp;lt;6.5% off any T2D medications. Nine of 17 patients with T2D failed to achieve remission by 12 months. After sample quality control, jejunal biopsies from 7 patients with T2D without remission (NR), 8 patients with diabetes remission (R) and 13 patients without diabetes (ND) were analyzed via RNA-seq. Significance was defined by an FDR cutoff of 0.05. Unsupervised principal components analysis (PCA) showed no significant differences across PC1 or PC2 among the 3 groups. However, among top pathways expressed in samples from patients with T2D remission (R), LXR/RXR pathway activation was upregulated (pathway z-score= 0.333, p= 4.85E-06) but downregulated in patients without diabetes (ND, z-score= -1.508, p=.01) and in patients without remission (NR, z-score=-1.0, p=2.07E-07). Antioxidant action of vitamin C exhibited a similar pattern of activation uniquely in R and not in NR or ND (R: p=.02, z-score=0.816; NR: p=0.33, z-score=0.816; ND: p=0.03, z-score=-1.0). In summary, although jejunal remodeling may occur in patients without T2D remission, lipogenic (LXR-driven) and antioxidative pathways are uniquely upregulated in biopsies from those with remission. We hypothesize that these processes may underlie mechanisms for T2D improvement after RYGB. Disclosure M.A.Stefater-richards: None. W.F.Gourash: None. A.Courcoulas: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R56DK125816, R01DK108642, K08DK125878)

Therapeutic inertia related to the injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes in UK primary care.

To determine the extent of therapeutic inertia related to the weekly injectable glucagon-like peptide-1 receptor agonists dulaglutide and semaglutide in patients with type 2 diabetes (T2D) in the United Kingdom. Adults with T2D who received their first primary care prescription of dulaglutide or semaglutide between January and July 2019 were identified from the UK Clinical Practice Research Datalink GOLD primary care database. Doses prescribed, glycated haemoglobin (HbA1c), body mass index (BMI) and concomitant T2D medications were assessed at first prescription and at 3, 6 and 9months. Of the patients prescribed dulaglutide (N=748; mean [SD] age 59.0 [11.2] years) and semaglutide (N=437; mean [SD] age 58.4 [10.6] years), 93.0% and 89.0%, respectively, had an HbA1c level ≥7.5%(≥58.46mmol/mol), and 56.4% and 54.9%, respectively, had an HbA1c level ≥9.0%(≥74.86mmol/mol), at first prescription. At 6 to 9 months, 75.0% of those on dulaglutide 0.75 mg and 57.6% of those on semaglutide 0.25 mg or 0.5 mg had an HbA1c level ≥7.5%(≥58.46mmol/mol). At 9 months, 21.9% of the dulaglutide cohort were on the suboptimal dose of 0.75 mg, and 46.1% of the semaglutide cohort were on the suboptimal doses of 0.25 mg or 0.5mg. Multiple examples of therapeutic inertia were identified, including first prescription at HbA1c levels considerably above target and failure to escalate to optimal doses even with evidence of suboptimal metabolic control. A substantial proportion of patients therefore did not achieve optimal HbA1c targets.

Type 2 Diabetes and the Microbiome.

Diabetes represents one of the most significant, and rapidly escalating, global healthcare crises we face today. Diabetes already affects one-tenth of the world's adults-more than 537 million people, numbers that have tripled since 2000 and are estimated to reach 643 million by 2030. Type 2 diabetes (T2D), the most prevalent form, is a complex disease with numerous contributing factors, including genetics, epigenetics, diet, lifestyle, medication use, and socioeconomic factors. In addition, the gut microbiome has emerged as a significant potential contributing factor in T2D development and progression. Gut microbes and their metabolites strongly influence host metabolism and immune function, and are now known to contribute to vitamin biosynthesis, gut hormone production, satiety, maintenance of gut barrier integrity, and protection against pathogens, as well as digestion and nutrient absorption. In turn, gut microbes are influenced by diet and lifestyle factors such as alcohol and medication use, including antibiotic use and the consumption of probiotics and prebiotics. Here we review current evidence regarding changes in microbial populations in T2D and the mechanisms by which gut microbes influence glucose metabolism and insulin resistance, including inflammation, gut permeability, and bile acid production. We also explore the interrelationships between gut microbes and different T2D medications and other interventions, including prebiotics, probiotics, and bariatric surgery. Lastly, we explore the particular role of the small bowel in digestion and metabolism and the importance of studying small bowel microbes directly in our search to find metabolically relevant biomarkers and therapeutic targets for T2D.

Real-world characteristics, modern antidiabetic treatment patterns, and comorbidities of patients with type 2 diabetes in central and Eastern Europe: retrospective cross-sectional and longitudinal evaluations in the CORDIALLY® study

BackgroundGuidelines from 2016 onwards recommend early use of SGLT2i or GLP-1 RA for patients with type 2 diabetes (T2D) and cardiovascular disease (CVD), to reduce CV events and mortality. Many eligible patients are not treated accordingly, although data are lacking for Central and Eastern Europe (CEE).MethodsThe CORDIALLY non-interventional study evaluated the real-world characteristics, modern antidiabetic treatment patterns, and the prevalence of CVD and chronic kidney disease (CKD) in adults with T2D at nonhospital-based practices in CEE. Data were retrospectively collated by medical chart review for patients initiating empagliflozin, another SGLT2i, DPP4i, or GLP-1 RA in autumn 2018. All data were analysed cross-sectionally, except for discontinuations assessed 1 year ± 2 months after initiation.ResultsPatients (N = 4055) were enrolled by diabetologists (56.7%), endocrinologists (40.7%), or cardiologists (2.5%). Empagliflozin (48.5%) was the most prescribed medication among SGLT2i, DPP4i, and GLP-1 RA; > 3 times more patients were prescribed empagliflozin than other SGLT2i (10 times more by cardiologists). Overall, 36.6% of patients had diagnosed CVD. Despite guidelines recommending SGLT2i or GLP-1 RA, 26.8% of patients with CVD received DPP4i. Patients initiating DPP4i were older (mean 66.4 years) than with SGLT2i (62.4 years) or GLP-1 RA (58.3 years). CKD prevalence differed by physician assessment (14.5%) or based on eGFR and UACR (27.9%). Many patients with CKD (≥ 41%) received DPP4i, despite guidelines recommending SGLT2is owing to their renal benefits. 1 year ± 2-months after initiation, 10.0% (7.9–12.3%) of patients had discontinued study medication: 23.7–45.0% due to ‘financial burden of co-payment’, 0–1.9% due to adverse events (no patients discontinued DPP4i due to adverse events). Treatment guidelines were ‘highly relevant’ for a greater proportion of cardiologists (79.4%) and endocrinologists (72.9%) than diabetologists (56.9%), and ≤ 20% of physicians consulted other physicians when choosing and discontinuing treatments.ConclusionsIn CORDIALLY, significant proportions of patients with T2D and CVD/CKD who initiated modern antidiabetic medication in CEE in autumn 2018 were not treated with cardioprotective T2D medications. Use of DPP4i instead of SGLT2i or GLP-1 RA may be related to lack of affordable access, the perceived safety of these medications, lack of adherence to the latest treatment guidelines, and lack of collaboration between physicians. Thus, many patients with T2D and comorbidities may develop preventable complications or die prematurely.Trial registration NCT03807440.

600-P: Examining Beliefs about Type 2 Diabetes Medications: A Multidimensional Approach

Background: Beliefs about type 2 diabetes (T2D) medications predict treatment adherence; yet, factors that influence these beliefs are poorly understood. Further, prior studies reduce the complex interplay between beliefs about treatment necessity and medication-related concerns to a single dimension by using a difference score. This study examined correlates of T2D medication beliefs and modeled the multidimensional associations of beliefs and adherence. Methods: Participants were 812 primarily disadvantaged and ethnic minority adults with T2D (Female = 56.9%; Latino = 86.5%; Mean [SD] Age and A1C = 59.2 [10.8], 9.3 [1.8], respectively) recruited for a self-management trial. Informed by the Common Sense Model and prior research, relations of patient- and illness-related factors with medication beliefs (Horne, Weinman, Hankins, 1999) were examined using linear regression. Confirmatory and exploratory polynomial regression examined associations of medication beliefs and self-reported adherence. Results: Hispanic ethnicity (p &amp;lt; .01) , insulin use (p &amp;lt; .05) , greater number of medications (p &amp;lt; .05) , and lower levels of education (p &amp;lt; .05) were associated with stronger necessity beliefs. Lower income (p &amp;lt; .05) and Hispanic ethnicity (p &amp;lt; .01) were associated with greater concerns. Adherence was lowest among those with strong concerns and weak necessity beliefs. Non-reciprocal effects were also observed, which could not have been assessed using a difference score. Patients with ambivalent beliefs had lower adherence than those with indifferent beliefs. Discussion: Indicators of lower SES were associated with concerns about T2D medications. Increased disease severity and Hispanic ethnicity were associated with stronger necessity beliefs. However, Hispanics also reported more concerns about their medications. Results further support use of polynomial regression to assess medication beliefs and adherence. Addressing concerns, in particular, may enhance T2D medication adherence. Disclosure A.G.Asman: None. L.A.Phillips: None. E.A.Walker: None. L.D.Pappalardo: None. J.S.Gonzalez: Consultant; Virta Health Corp. Funding National Institutes of Health (R18 DK098742) Einstein–Mount Sinai Diabetes Research Center (P30 DK020541) New York Regional Center for Diabetes Translation Research (P30 DK111022) J.S.G. is supported by National Institutes of Health (RDK104845, RDK121298, RDK121896)

1245-P: Outcomes among Veterans with T2D at Time of Departure from Virtual Clinic: A Nationwide, Real World Study

Lifestyle interventions for type 2 diabetes (T2D) typically have poor retention, and drop out is often assumed to indicate treatment failure. A partnership between the Veterans Health Administration and Virta Health allows Veterans with T2D to enroll in Virta's clinic, which provides carbohydrate restricted nutrition therapy via continuous remote care. We sought to assess change in clinical outcomes upon clinic departure using medical record data. Percent change in clinical outcomes on a per patient basis from enrollment to time of departure were assessed with one sample t tests. Among 677 enrolled Veterans, 270 (40.0%) departed the clinic within 2 years (283±184 days in treatment; enrollment: age 58±9y, 13% female, 235±47 lb, 179±86 mg/dl glucose, 2.3±0.9 T2D medications) . Weight was significantly reduced at time of departure in all groups initiating nutrition therapy (p&amp;lt;0.05) , although clinically significant weight loss was only achieved among those who left after one year (Table 1) . Percent change in blood glucose was unchanged (p&amp;gt;0.05) despite lower mean glucose which occurred concurrent with medication deprescription in most groups (p&amp;lt;0.05) . These results show that Veterans initiating therapy experienced clinical improvements prior to clinic departure and return to standard care, particularly in weight after one year of treatment and in reduced need for medication to maintain glycemia. Disclosure B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp.

900-P: Patterns of Drug Utilization for Cardio- and Renal-Protective Antihyperglycemic Agents in a Commercially Insured Population

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter-2 inhibitors (SGLT2i) have cardioprotective and kidney-protective effects in select patients with type-2 diabetes (T2D) . Appropriate use, and cost-effectiveness, is essential to realize these benefits as well as to manage total healthcare spending. Methods: For a commercially insured population (≥18 years old) enrolled in a virtual accountable care organization (Level2) , we examined de-identified administrative claims in a research database for Type-2 diabetes medications from 12/01/20to 11/30/2021. We determined the TCoC for this population, as well as changes in spending and utilization by medication class. Results: Among 7,361 individuals attributed to Level2, 1,735 members (23.6%) had a cardiovascular or renal indication for an GLP-1RA or SGLT2i. In this population, 447 were prescribed a GLP-1RA and 385 were prescribed a SGLT2i, representing 25.8% and 22.2% of those with comorbidity indications for each drug, respectively. Additionally, 1,214 individuals were prescribed a GLP-1RA and 1,214 were prescribed a SGLT2i without cardiovascular or renal indications, representing 35% of these prescriptions combined. Conclusion: In 2019-21, use of GLP-1RA and SGLT2i remained limited to approximately 1 in 4 commercially insured patients with T2D and a cardiovascular or renal indication for their selection. Further, they were commonly used in the absence of cardiovascular or renal indication for these classes of agents. While nondiabetes indications for these drugs (weight-loss and renal disease) have expanded recently (April-June 2021) , those broader indications were not in place for the majority of the study period. In a time of limited resources, guideline-concordant therapy is critical to improving the health of those with indications as well as reducing less-than-appropriate use. Disclosure D.J.Cook: None. A.Defail: Employee; Level2. E.Macfarlane: Employee; Level2. D.Pederson: Employee; Level2.

Adapting Medication for Type 2 Diabetes to a Low Carbohydrate Diet.

Healthcare professionals in the primary care setting need to be competent to safely adapt diabetes medications when patients with Type 2 Diabetes (T2D) alter their diet. Safe prescribing practice is supported through an understanding of the clinical evidence, basic science, and pharmacology of medications. This review article supports clinicians in the practical application of this knowledge to achieve safe practice. Traditional medical training and clinical practice for chronic disease has long revolved around the teaching of intensifying therapy and evidenced based prescribing, a crucial skill when chronic disease progresses. Now that we are witnessing remission of Type 2 Diabetes through nutritional interventions specifically low carbohydrate diets (LCD) we must apply the same effort and thought to de-prescribing as the underlying metabolic condition improves. There is minimal guidance in the literature on how to actively de-prescribe. The American Diabetes Association in their Standards of Medical Care in Diabetes–2021 acknowledges low carbohydrate nutritional therapy (LCD) as a viable option in the management of Type 2 Diabetes (T2D). Thus, the goal of our paper is to help close the gap between the clinical evidence, basic science, and pharmacology of T2D medications to the practical application and teamwork needed to facilitate safe medication reduction in the primary care setting when applied to a LCD. The LCD is an increasingly popular and effective option for managing T2D and can lead to an improvement in the condition, reduced medication burden, and contribute to significant weight loss. Safe initiation of a LCD in patients on medications requires significant monitoring and medication adjustments to decrease and eliminate the risk of hypoglycemia and hypotension. The health care team including clinicians in primary care, nursing, pharmacy and nutrition need to be competent in adjusting diabetes and antihypertensive medications to achieve safe and effective care. The most immediate and important adjustments are to insulin, sulfonylureas, SGLT2 inhibitors, blood pressure medications and diuretics. Interdisciplinary care teams can individualize therapy while following the guidance, which includes monitoring blood glucose and blood pressure closely, decreasing medications that can cause hypoglycaemia and hypotension, evaluating blood glucose and blood pressure data responses regularly, and open access communication with the team. The article is an international consensus document on de-prescribing that was put together by a multidisciplinary team of clinicians.

Heart failure documentation in outpatients with diabetes and volume overload: an observational cohort study from the Diabetes Collaborative Registry

BackgroundHeart failure is a common and devastating complication of type 2 diabetes (T2D). Prompt recognition of heart failure may avert hospitalization, facilitate use of guideline-directed therapies, and impact choice of T2D medications. We sought to determine the rate and factors associated with heart failure documentation in T2D patients with evidence of volume overload requiring loop diuretics.MethodsDCR is an on-going, prospective US registry of outpatient T2D patients from > 5000 cardiology, endocrinology, and primary care clinicians (current analysis used data from 2013–2019). Among T2D patients receiving loop diuretics, we examined the rate of chart documentation of heart failure. We used a 3-level hierarchical logistic regression model (patients nested within physician within practice) to examine factors associated with heart failure diagnosis.ResultsAmong 1,322,640 adults with T2D, 225,125 (17.0%) were receiving a loop diuretic, of whom 91,969 (40.9%) had documentation of heart failure. Male sex, lower body mass index, atrial fibrillation, chronic kidney disease, and coronary artery disease were associated with greater odds of heart failure diagnosis. After accounting for patient factors, patients seen by cardiologists were the most likely to have HF documented followed by PCPs and then endocrinologists.ConclusionsAmong US outpatients with T2D, 17% of patients had evidence of volume overload—defined by loop diuretic prescription—of whom fewer than half had a clinical diagnosis of heart failure. While there may be non-heart failure indications for loop diuretics, our data suggest that a substantial proportion of T2D patients may have unrecognized heart failure and therefore could be missing opportunities for targeted therapies that could alter the clinical course of heart failure.