A1C Reduction Research Articles

THU244 Clinical Factors Affecting Dapagliflozin Response For Glycemic Control And Body Weight Reduction: Post-hoc Analysis Of BEYOND Study

Abstract Disclosure: K. Ahn: None. J. Ji Eun: None. J. In-Kyung: None. Background: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, ameliorates hyperglycemia and obesity by inhibiting renal glucose reabsorption. However, significant heterogeneity exists in glucose-lowering efficacy and the magnitude of the weight loss among patients with type 2 diabetes. Herein, we aimed to evaluate the clinical factors affecting response to dapagliflozin treatment. Methods: We performed a post-hoc analysis of the BEYOND (Effects of Dapagliflozin Compared with Glimepiride on Body Composition in Patients with Type 2 Diabetes Inadequately Controlled with Metformin) randomized, double-blind, parallel-group trial. Patients were randomly assigned (1:1) to receive the addition of either dapagliflozin 10 mg per day or glimepiride 1∼2 mg per day to background metformin therapy for 52 weeks. Changes in HbA1c and body weight from baseline during the observation period were assessed for all patients. Responder to dapagliflozin was defined by >1% reduction in A1c and >3% reduction in body weight at week 52. Then, we classified the total subjects into 4 groups: non-responder of both A1c reduction and body weight reduction, responders of A1c reduction but non-responder of body weight reduction, non-responder of A1c reduction but responders of body weight reduction, and responders of both A1c reduction and body weight reduction. Results: Among 56 patients in a dapagliflozin arm, 55.4% (N = 31) and 57.1% (N = 32) experienced clinical responses as indicated by reductions in HbA1c and in body weight reduction, respectively. Younger age and higher HbA1c level at baseline were significantly associated with a greater HbA1c reduction, and a higher estimated glomerular filtration rate (eGFR) was significantly associated with a greater body weight reduction. However, there was no association between the change in HbA1c and the change in body weight (r = −0.133, P = 0.328). Responders of both A1c reduction and body weight reduction were most common (32.1%), non-responders of A1c reduction but responders of body weight reduction were second-most (25.0%), responders of A1c reduction but non-responders of body weight reduction were 23.2%, and non-responders of both A1c reduction and body weight reduction were 19.6%. Subjects with higher fasting plasma glucose (FPG) and HbA1c in addition to lower eGFR at baseline had a greater reduction in HbA1c, but less reduction in body weight. Conversely, those with lower FPG and HbA1c in addition to higher eGFR at baseline had a greater reduction in body weight, but less reduction in HbA1c level. Conclusion: Patients with type 2 diabetes actually exhibit a heterogeneous response to dapagliflozin treatment. Glucose-lowering efficacy of dapagliflozin was associated with worse baseline glycemic status, and body weight reduction was associated with baseline higher eGFR. Presentation: Thursday, June 15, 2023

THU255 Tirzepatide-induced Weight Loss In A Type 2 Diabetic Taking Oral Contraceptives

Abstract Disclosure: A. Arunachalam: None. A. Nguyen: None. N.L. Shah: None. Obesity is a global health challenge which can lead to type 2 diabetes, hypertension, cardiovascular disease, and decreased life expectancy. In addition to lifestyle intervention, pharmacotherapy to sustain weight loss has remained limited due to effectiveness, cost, and adverse effects. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like-peptide-1 receptor agonist currently approved for type 2 diabetes treatment. Tirzepatide-induced weight loss may provide new options for treatment of obesity. We report a 32-year-old female with a history of T2DM and PCOS originally on metformin who was started on semaglutide 0.25 mg, which was uptitrated to 0.5mg weekly for 6 months. She lost 25 lbs with no side effects. Semaglutide and OCPs were discontinued due to fertility with her weight and hemoglobin A1C rebounding off medication. She was started on tirzepatide 2.5mg weekly. At that time, she weighed 223 lbs with a hemoglobin A1C 8.2%. She was counseled to resume OCPs and improve glucose control and weight reduction prior to attempting to conceive. Once increased tirzepatide dosing to 5mg weekly, she endorsed severe nausea and intermittent epigastric abdominal pain on day of injection. She attempted to increase dose to 7.5mg weekly, but dose was reduced due to complaints of constipation and worsened abdominal pain requiring bowel regimen. She remained on tirzepatide for a total of 4 months prior to becoming pregnant while on oral contraceptives. Her weight decreased from 223 to 212 lbs with reduction in hemoglobin A1C from 8.2% to 6.1%. While initially studied for use in type 2 diabetes, tirzepatide was found to induce clinically significant weight reduction. The recent SURMOUNT-1 trial, which studied the effects of tirzepatide in non-diabetics, demonstrated that once-weekly tirzepatide at three different doses demonstrated substantial and sustained weight reduction in patients with obesity. In trials involving patients with once-weekly injectable semaglutide, the mean reduction in hemoglobin A1C was 1.8 percentage points and reduction in mean body weight was 6.5 kg. In the SURPASS-2 trial, reductions in body weight were greater with tirzepatide when compared to semaglutide with mean estimated treatment difference −1.9kg, -3.6kg, and -5.5 kg respectively based on dosing of 5mg, 10mg, and 15mg. The adverse events most commonly reported in patients on tirzepatide include nausea, vomiting, and diarrhea, which occurred most commonly during dose-escalation. Mounjaro is known to reduce the efficacy of oral contraceptive pills due to delayed gastric emptying. This delay is largest after the first dose so recommended to switch from oral to non-oral contraceptives for the first four weeks when tirzepatide is initiated. It is important to counsel patients on the decreased efficacy of oral contraceptives while on tirzepatide. <!--EndFragment--> Presentation: Thursday, June 15, 2023

SAT105 Frequent Monitoring Of Blood Glucose Levels Via A Remote Patient Monitoring System Helps Improve Glycemic Control

Abstract Disclosure: I. Sachmechi: None. M. Amini: None. S. Salam: None. R. Khan: None. A. Spitznogle: None. T. Belen: None. Objective: This study aims to evaluate the effectiveness of the Vivovitals telehealth platform on improving glycemic control and reducing A1C in patients with uncontrolled type II diabetes mellitus by providing more accessible and frequent patient care under the monitoring by their physician. Methods: This 12-week, prospective, pragmatic, single-center, double-arm study assessed the impact of the Vivovitals diabetes platform on glycemic control among 78 adults ≥ 18 years of age, with A1C ≥ 7.5% (58 mmol/mol) at baseline. The participants were randomized into two groups. The control group received standard care, while the intervention group was assisted to install the application on their smartphones and connect it to a Bluetooth Glucometer, and access to an online data portal. Blood glucose measurements were transmitted to the provider daily. Patients were contacted twice weekly regardless of their blood sugar measurements and additional call was made if blood glucose levels were <70 mg/dL or >180 mg/dL and modifications were made to diet and medication. The control group was allowed to call the provider if they have questions regarding their blood sugar levels or their medications. The two groups were compared at baseline and 12 weeks using nonparametric tests with p<0.05 considered statistically significant. Results: The mean A1C in the intervention group (n=39) was 9.53 (81 mmol/mol) +1.68 at baseline. Post-trial, mean A1C decreased to 7.99 (64 mmol/mol) + 1.40 (p < 0.001). In comparison, the mean A1C in the control group (n=39) was 9.63 (64 mmol/mol) + 1.47 at baseline with little change in post-trial mean A1C averaging 9.16 (77 mmol/mol) + 1.51 (p = 0.87). Discussion: In this study, patients who utilized the Vivovitals platform saw a significant decrease in A1C at an average of 1.56% compared to the non-significant 0.47% A1C reduction in the control group participants. We believe the A1C-reducing effect in the intervention group was due to the more frequent interactions with the physician and subsequent medication adjustments based on the data provided. The Vivovitals platform allows an affordable closer monitoring of blood glucose levels, identification of the direction of glycemic trends, and earlier intervention. While not explored in this study, it is reasonable to believe that the use of the Vivovitals diabetes platform could reduce Emergency Department visits and inpatient hospitalizations for hypoglycemia or hyperglycemia as the clinician can intervene before a patient becomes symptomatic. Conclusion: We conclude that the Vivovitals platform may help to reduce A1C in adults with uncontrolled type 2 diabetes mellitus in conjunction with lifestyle modifications and anti-diabetic medications. Presentation: Saturday, June 17, 2023

THU295 The Role Of Imatinib In Pediatric Diabetes

Abstract Disclosure: K. Lavelle: None. C. Chamberlain: None. M.S. Anderson: None. M.S. German: None. A. Nip: None. S.E. Gitelman: None. Background: A growing body of evidence suggests that imatinib may attenuate or even reverse diabetes in both mice and adults. In children, however, this has not been reported yet. Clinical Case: A 14-year-old previously healthy Black male presented to the hospital with a 2-week history of polydipsia, polyuria, and weight loss. He had no family history of diabetes. On admission, he was underweight (weight 45th percentile, Z=-0.11; BMI 1st percentile, Z=-2.33) and was found to be in DKA (serum pH 7.15 [7.31-7.47], glucose 560mg/dL [65-99 mg/dL], HCO3 9.7 mEq/L [20-28 mEq/L], urine ketones 4+, Hgb A1c 12.3%, C-peptide <0.2 ng/mL [1.1-4.4 ng/mL]) as well as COVID-19 positive and G6PD deficient with hyperleukocytosis (WBC 137.8 TH/mm3 [5-10 TH/mm3]). He was requiring 0.6u/kg/day insulin upon discharge and went home on glargine 10 units daily, aspart insulin-to-carbohydrate ratio 1u:10g at breakfast, 1:12 at lunch, and 1:15 at dinner with insulin sensitivity factor 1u:50 mg/dL. After discharge, autoantibodies (GAD-65, IA-2, IAA, ZnT8) returned negative. Oncologic testing returned positive for myeloid neoplasm, and he was readmitted for initiation of imatinib 400mg/day 2 months post-discharge. Over the next 3 months, his Hgb A1c decreased from 6.3% to 4.9%. The following month, he had gained weight (weight 83rd percentile, Z=0.95; BMI 61st percentile, Z=0.27) and was requiring only 0.2u/kg/day insulin on a non-restricted diet. His Hgb A1c was down to 4.6% without hypoglycemia 6 months after starting imatinib. Conclusion: Imatinib is a tyrosine kinase inhibitor first approved for treatment of chronic myeloid leukemia. In vivo studies have demonstrated that it targets anti-diabetic pathways as well: imatinib inhibits c-Abl in pancreatic beta cells, thereby blunting endoplasmic reticulum stress responses and reducing apoptosis. It also inhibits platelet-derived growth factor receptors, thereby increasing adiponectin and improving insulin sensitivity. Mouse studies have shown prevention of Type 1 diabetes (T1D) and reversal of both T1D and Type 2 diabetes with imatinib. A phase 2 trial in adults with new onset T1D treated with imatinib for 6 months showed preservation of beta cell function out to 12 months (Gitelman et al, Lancet Diabetes 2021). While receiving imatinib, participants also saw lower Hgb A1c, less insulin use, higher adiponectin and lower proinsulin:C-peptide, and improved beta cell glucose sensitivity when compared to the placebo group. This case suggests that imatinib might similarly benefit children, as our patient experienced a 1.7-point reduction in Hgb A1c% and a 67% reduction in insulin requirement on therapy. It is the first case to describe imatinib use in an adolescent with diabetes and poses two important questions: what is the etiology of diabetes in this patient, and how might imatinib impact the natural course of disease? Further studies are underway to clarify these issues. Presentation: Thursday, June 15, 2023

Carbohydrate counting implementation on pediatric type 1 diabetes mellitus: systematic review and meta-analysis.

Type 1 diabetes mellitus, which is the most common type of diabetes among children, is not curable but can be managed well without a negative effect on quality of life. One of the treatments of type 1 diabetes mellitus is carbohydrate counting. This systematic review and meta-analysis sought to evaluate the efficacy of carbohydrate counting with regard to hemoglobin A1c (HbA1c) reduction in children with type 1 diabetes mellitus. Nine studies were assessed, with the primary outcome being glycemic control (HbA1c changes). We searched the following electronic databases: ProQuest, PubMed, Scopus, and ScienceDirect. The quality of studies included was assessed using the risk of bias for randomized control trials and the JBI Critical Appraisal Checklist for observational and cross-sectional studies. Quantitative analyses were made and extrapolated into a forest plot. A total of 1,693 articles were identified. Four reviewers independently screened titles and abstracts. Of the 36 articles screened, 34 articles were found to be eligible. Of these, 25 studies were excluded because of unsuitable outcomes and study designs. Nine articles were included in the final analysis. Meta-analysis showed that there was a reduction in HbA1c in the carbohydrate counting group as compared to the control group. The cumulative effect of carbohydrate counting on HbA1c was a mean difference of -0.55 (95% confidence interval, -0.81 to -0.28, P<0.001). All of the studies exhibited similar results with the mean difference reduction favoring the interventional group. However, the heterogeneity analysis revealed an I2 value of 88%, implying high heterogeneity in the meta-analysis. The meta-analysis showed evidence favoring the use of carbohydrate counting in the management of type 1 diabetes mellitus.

Digital Twin-Enabled Personalized Nutrition Improves Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes: Results of a 1-Year Randomized Controlled Study

ObjectivePostprandial hyperglycemia drives insulin resistance and inflammation, leading to metabolic dysfunction-associated fatty liver disease (MAFLD). Prediction of postprandial glycemic responses by digital twin (DT) technology can fashion a personalized nutrition, activity, and sleep to treat type 2 diabetes (T2D) and MAFLD. This study examines the effects of DT-enabled personalized nutrition, activity, and sleep on glycemic status, surrogate markers of MAFLD, and magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with T2D. MethodsIn an open-label randomized trial (2:1), 319 people with T2D were eligible to intervention (DT) or standard care (SC). DT patients followed personalized meal plans with foods suggested by artificial intelligence with least predicted postprandial glycemic response. The primary end point was to compare change in hemoglobin A1c (HbA1c) and medicine reduction between the DT and SC groups. Key secondary end points included remission to compare liver function test scores and visceral adiposity using MRI. ResultsHbA1C was significantly better for DT than for SC (−2.9 [1.8] vs −0.3 [1.2]; P < .001) at 1 year with 72.7% remission of T2D. In patients with abnormal baseline values, significant improvements were seen in DT vs SC patients from baseline to 1 year in nonalcoholic fatty liver disease liver fat score (mean [SD]; −2.5 [2.0] vs −0.1 [1.5]; P < .001) and nonalcoholic fatty liver disease fibrosis score (−1.20 [0.9] vs −0.1 [1.0]; P < .001), respectively. Improvements are seen with DT compared with SC in other liver fat, fibrosis score, and %liver fat by MRI-PDFF. ConclusionAt 1 year, DT-enabled personalized treatment significantly improved hyperglycemia and surrogate markers of MAFLD and MRI-PDFF.

Effects of continuous positive airway pressure therapy on glucose metabolism in patients with obstructive sleep apnoea and type 2 diabetes: a systematic review and meta-analysis.

Obstructive sleep apnoea is a highly prevalent chronic disorder and has been shown to be associated with disturbed glucose metabolism and type 2 diabetes. However, the evidence from individual clinical trials on the effect of continuous positive airway pressure (CPAP) treatment on glycaemic control in patients with co-existing obstructive sleep apnoea and type 2 diabetes remains controversial. A systematic review of randomised controlled trials assessing the effect of CPAP on glycaemic control in patients with obstructive sleep apnoea and type 2 diabetes was conducted using the databases MEDLINE, Embase, Cochrane and Scopus up to December 2022. Meta-analysis using a random-effect model was performed for outcomes that were reported in at least two randomised controlled trials. From 3031 records screened, 11 RCTs with a total of 964 patients were included for analysis. CPAP treatment led to a significant reduction in haemoglobin A1c (HbA1c) (mean difference -0.24%, 95% CI -0.43- -0.06%, p=0.001) compared to inactive control groups. Meta-regression showed a significant association between reduction in HbA1c and hours of nightly CPAP usage. CPAP therapy seems to significantly improve HbA1c and thus long-term glycaemic control in patients with type 2 diabetes and obstructive sleep apnoea. The amount of improvement is dependent on the hours of usage of CPAP and thus optimal adherence to CPAP should be a primary goal in these patients.

Evaluating the Clinical Effect of Personal Continuous Glucose Monitoring in a Diverse Population With Type 2 Diabetes.

Objective: To determine the clinical effect of personal continuous glucose monitoring (CGM) in a diverse population with type 2 diabetes (T2D). Research Design and Methods: A report was created from the electronic health record identifying adults prescribed CGM at an urban family medicine clinic between January 1, 2019, and February 23, 2022. An "index date" was identified as the start of CGM. The closest hemoglobin A1c (A1c) 6 months or more after the index date was identified as the "follow-up date." The primary outcome of this study was to compare the percentage of individuals meeting the MN Community Measure (MNCM) D5 HbA1c goal of <8% at the follow-up date versus the index date. Results: Seventy-two patients were identified after the exclusion criteria were applied. Approximately one-third of patients required utilization of an interpreter and 76% of patients were of a racial or ethnic minority. The mean HbA1c prior to CGM use was 9.8%, with 16.7% of the population meeting the MNCM D5 A1c goal of <8%. At the follow-up date, the mean A1c was 8.4% (mean difference -1.4%; p < 0.001), with 41.7% of the population meeting goal (mean difference +25%; p < 0.001). Subgroup analyses affirm that the results of the primary outcome were sustained despite insulin use status. Conclusion: A diverse population with T2D had a significant reduction in A1c and was more likely to meet the MNCM D5 A1c goal of <8% after an average of 6 months using personal CGM.

Physiologic hormone administration improves HbA1C in Native Americans with type 2 diabetes: A retrospective study and review of insulin secretion and action.

Insulin is secreted in pulses from pancreatic beta-cells, and these oscillations maintain fasting plasma glucose levels within a narrow normal range. Within islets, beta-cells exhibit tight synchronization of regular oscillations. This control circuit is disrupted in type 2 diabetes, and irregularities in pulse frequency and amplitude occur. The prevalence of type 2 diabetes is three times higher in American Indian and Native Alaskans compared to Whites, and their genetic ancestry is associated with low beta-cell function. Obesity in this population compounds their vulnerability to adverse outcomes. The purpose of this article is to review insulin secretion and action and its interaction with race. We also present the results from a 6-month retrospective chart review of metabolic outcomes following intravenous physiologic hormone administration to 10 Native Americans. We found reductions in hemoglobin A1C (baseline: 9.03% ± 2.08%, 6months: 7.03% ± 0.73%, p = 0.008), fasting glucose (baseline: 176.0 ± 42.85 mg/dL, 6months: 137.11 ± 17.05 mg/dL, p = 0.02), homeostatic model assessment of insulin resistance (baseline: 10.39 ± 4.66, 6months: 7.74 ± 4.22, p = 0.008), and triglycerides (baseline: 212.20 ± 101.44, 6months: 165.50 ± 76.48 mg/dL, p = 0.02). Physiologic hormone administration may improve components of the metabolic syndrome. The therapy warrants investigation in randomized controlled trials.

Behavioral Sleep Interventions and Cardiovascular Risk Factors: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chronic sleep disturbance has been consistently associated with cardiovascular disease. We sought to determine whether behavioral interventions to improve sleep have been associated with improvements in 4 common cardiovascular disease risk factors: hypertension, diabetes mellitus (DM), obesity, and smoking. Randomized controlled trials evaluating the prospective effect of behavioral sleep interventions on ( a ) blood pressure in participants with hypertension/prehypertension, ( b ) glycemic control in participants with DM/pre-DM, ( c ) anthropometrics in participants who were overweight/obese, and ( d ) smoking status in smokers were eligible. Where feasible, we undertook random-effects meta-analyses of standardized mean differences in cardiovascular disease risk factor change. Overall, 3 trials met the inclusion criteria for blood pressure, 4 for glycemic control, 9 for overweight/obesity, and 2 for smoking. On meta-analysis, interventions with sleep as the sole behavioral target were associated with a significant reduction in hemoglobin A 1c % (-0.84; 95% confidence interval [CI], -1.34 to -0.34), but not a significant reduction in systolic blood pressure (-0.18; 95% CI, -0.55 to 0.20) versus controls. In addition, any interventions with sleep as a behavioral target were associated with significant reductions in hemoglobin A 1c % (-0.71; 95% CI, -1.01 to -0.42) and weight (-0.78; 95% CI, -1.11 to -0.45), but not systolic blood pressure (-0.72; 95% CI, -1.82 to 0.37). Trials evaluating smoking status were not amenable to meta-analysis. Behavioral interventions to improve sleep were associated with improved glycemic control in patients with DM. It is also possible that these interventions improve weight in individuals who were overweight/obese. A low number of trials and small sample sizes indicate that further large, well-designed randomized controlled trials of interventions are warranted.

Effectiveness of self-management interventions for long-term conditions in people experiencing socio-economic deprivation in high-income countries: a systematic review and meta-analysis.

Long-term conditions (LTCs) are prevalent in socio-economically deprived populations. Self-management interventions can improve health outcomes, but socio-economically deprived groups have lower participation in them, with potentially lower effectiveness. This review explored whether self-management interventions delivered to people experiencing socio-economic deprivation improve outcomes. We searched databases up to November 2022 for randomized trials. We screened, extracted data and assessed the quality of these studies using Cochrane Risk of Bias 2 (RoB2). We narratively synthesized all studies and performed a meta-analysis on eligible articles. We assessed the certainty of evidence using GRADE for articles included in the meta-analysis. The 51 studies included in this review had mixed findings. For the diabetes meta-analysis, there was a statistically significant pooled reduction in haemoglobin A1c (-0.29%). We had moderate certainty in the evidence. Thirty-eight of the study interventions had specific tailoring for socio-economically deprived populations, including adaptions for low literacy and financial incentives. Each intervention had an average of four self-management components. Self-management interventions for socio-economically deprived populations show promise, though more evidence is needed. Our review suggests that the number of self-management components may not be important. With the increasing emphasis on self-management, to avoid exacerbating health inequalities, interventions should include tailoring for socio-economically deprived individuals.

Predictors of Responsiveness to GLP-1 Receptor Agonists in Insulin-Treated Patients with Type 2 Diabetes.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are potent antihyperglycemic agents with beneficial effects on weight, cardiovascular, and renal outcomes. Physicians lack guidance as to which patients with insulin-requiring type 2 diabetes will respond best to GLP-1 RAs with respect to glycemic control, insulin dose reduction, and weight loss. This study evaluated the efficacy of GLP-1 RAs in patients with type 2 diabetes on insulin and patient factors that may predict a beneficial clinical response. Adults with type 2 diabetes treated with insulin who had a GLP-1 RA added to their regimen were evaluated retrospectively. Baseline parameters and outcomes at 3, 6, and 12 months were collected. Among the 81 patients included, there was a mean reduction in hemoglobin A1C of 0.94% (SD, 0.26; p = 0.0007), 0.40% (SD, 0.21; p = 0.0636), and 0.58% (SD, 0.23, p = 0.0154) at 3, 6, and 12 months, respectively, following the addition of a GLP-1 RA. There was also a reduction in body weight noted at each time point. Baseline characteristics including BMI, duration of diabetes, and insulin requirement did not significantly affect A1C reduction when GLP-1 RA was added. At 3 months, patients with a random C-peptide that was normal (≥0.8 ng/ml) were significantly more likely to have discontinued insulin than those with random C-peptide that was low (<0.8 ng/ml) (11 of 23 vs. 0 of 7 patients, p = 0.029). The addition of a GLP-1 RA reduced HbA1C, weight, and insulin requirements in this cohort of patients with type 2 diabetes on insulin. BMI, baseline insulin dose, and diabetes duration did not predict response. A C-peptide level ≥ 0.8 ng/ml predicted a beneficial response after 3 months of therapy.

The ACTIVATE Digital Health Pilot Program for Diabetes and Hypertension in an Underserved and Rural Community.

Community health centers and patients in rural and agricultural communities struggle to address diabetes and hypertension in the face of health disparities and technology barriers. The stark reality of these digital health disparities were highlighted during the coronavirus disease 2019 pandemic. The objective of the ACTIVATE (Accountability, Coordination, and Telehealth in the Valley to Achieve Transformation and Equity) project was to codesign a platform for remote patient monitoring and program for chronic illness management that would address these disparities and offer a solution that fit the needs and context of the community. ACTIVATE was a digital health intervention implemented in three phases: community codesign, feasibility assessment, and a pilot phase. Pre- and postintervention outcomes included regularly collected hemoglobin A1c (A1c) for participants with diabetes and blood pressure for those with hypertension. Participants were adult patients with uncontrolled diabetes and/or hypertension (n = 50). Most were White and Hispanic or Latino (84%) with Spanish as a primary language (69%), and the mean age was 55. There was substantial adoption and use of the technology: over 10,000 glucose and blood pressure measures were transmitted using connected remote monitoring devices over a 6-month period. Participants with diabetes achieved a mean reduction in A1c of 3.28 percentage points (standard deviation [SD]: 2.81) at 3 months and 4.19 percentage points (SD: 2.69) at 6 months. The vast majority of patients achieved an A1c in the target range for control (7.0-8.0%). Participants with hypertension achieved reductions in systolic blood pressure of 14.81 mm Hg (SD: 21.40) at 3 months and 13.55 mm Hg (SD: 23.31) at 6 months, with smaller reductions in diastolic blood pressure. The majority of participants also reached target blood pressure (less than 130/80). The ACTIVATE pilot demonstrated that a codesigned solution for remote patient monitoring and chronic illness management delivered by community health centers can overcome digital divide barriers and show positive health outcomes for rural and agricultural residents.

Implementing Effective Care Through Utilization of Diabetes-Focused "Right Care" Visits in a Suburban Primary Care Setting.

Background: Diabetes is the seventh leading cause of death in the United States and the leading cause of lower limb amputations, adult-onset blindness, and renal failure. It is estimated that 34.2 million Americans have a diabetes diagnosis, and the prevalence of this condition has continually increased over the last two decades. This study includes patients at a large, suburban primary care practice in southwest Ohio who were considered to have uncontrolled diabetes based on their last Hemoglobin A1c of greater than 9%. Compliance with recommended annual screenings among this population was 15%. Objectives: The aim of this project was to improve glycemic control and increase the number of patients who received the recommended annual screenings through the implementation of nurse practitioner-driven, diabetes-focused "Right Care" visits.C Methods: This quality improvement pilot study consisted of interventions implemented over the four plan-do-study-act cycles. Each cycle included a test of change that was identified based on data from previous cycles to ensure continuous improvement throughout project implementation. Four interventions were evaluated including the utilization of a diabetes registry, implementation of a "Right Care" checklist during "Right Care" visits, use of a patient engagement tool with a focus on individualizing diabetes medication regimens, and implementation of a team-engagement plan. Results: Average Hemoglobin A1c reduction was 2.4% post-"Right Care" visit. Compliance with the annual screening bundle increased to 44% over 8 weeks. Utilization of the patient/provider relationship increased visit compliance by 18%, and the team engagement plan decreased work-related stress by 12%. Conclusions: The implementation of "Right Care" visits led to improved glycemic control and increased compliance with the recommended annual screenings among patients with an A1c greater than 9%. The patient engagement tool identified key factors related to diabetes medication adherence and team engagement decreased work-related stress and improved annual fundoscopic exam screening compliance. Implications for Nursing: Nurse practitioner-led "Right Care" visits utilize the knowledge and skills of advanced practice registered nurses to improve glycemic control in patients with uncontrolled diabetes.

Analytical Method Development by HPLC to Evaluate the Stress Degradation Stability Profile of Ertugliflozin

Diabetes is a chronic disease in which the body does not make or properly utilize the insulin, a hormone that is required to convert blood sugar, starches, and other food into energy by circulate the glucose from blood into the body cells”. People are going on making new drugs and new formulations of the existing drugs within very short period of time. To get the regulatory permission for marketing, company has to submit required data including the analysis reports as to prove that their drug product is of required quality for its intended use. T2DM, the predominant type of diabetes accounting for &gt;90% of all diabetes cases, is a progressive disease involving parallel defects of glucose metabolism in multiple tissues. Common risk factors for T2DM include increasing age, smoking, being overweight or obese, physical inactivity and poor nutrition. Ertugliflozin is an oral, selective inhibitor of sodium glucose co-transporter-2 (SGLT2) which inhibits renal glucose reabsorption and results in urinary glucose excretion (UGE) and reductions in plasma glucose and haemoglobin A1c (A1C) in patients with type 2 diabetes mellitus (T2DM).The present developed analytical method was developed using 0.1% Formic acid in water: 0.1% Formic acid in ACN as the mobile phase. The developed method was found to be sensitive and time and cost effective with the reduced the use of organic chemicals in the mobile phase. Improved stability-indicating RP-HPLC method was developed for the estimation of ertugliflozin. Retention times compared to the best method reported. The developed method could be suitable for routine analysis of the drugs in bulk and tablet formulation after complete validation as per ICH guideline.

179-OR: Improved A1C and TIR with Once-Weekly Insulin Icodec vs. Insulin Glargine U100 in Insulin-Naïve T2D—ONWARDS 1

Long-term efficacy and safety of once-weekly insulin icodec (icodec) vs insulin glargine U100 (IGlar), both with non-insulin glucose-lowering agents, including SGLT2i and GLP‑1 RA, were assessed in this randomized, open-label, treat-to-target phase 3a trial (52-week + 26-week extension) in insulin-naïve adults with T2D (NCT04460885). Participants (n=984) were randomized 1:1 to icodec or IGlar. Prespecified primary analysis at week 52 showed A1C reduction from a baseline (BL) of 8.5% to 6.9% with icodec vs 8.4% to 7.1% with IGlar (estimated treatment difference [ETD]: −0.19%-points [95% CI: −0.36, −0.03]), confirming non‑inferiority (p&amp;lt;0.0001) and superiority (p=0.0210) of icodec. Time spent in target glycemic range (TIR, from week 48-52) was significantly improved to 72% (icodec) vs 67% (IGlar), confirming superiority; ETD 4.27%-points (95% CI: 1.92; 6.62, p=0.0004). There were no significant differences in mean weekly insulin dose (week 50-52), or in body weight change from BL. Level 2 or 3 hypoglycemia rates (BL to week 52) were low in both groups, with numerically higher rates with icodec. A higher proportion achieved A1C &amp;lt;7% without level 2 or 3 hypoglycemia with icodec vs IGlar (52.6% vs 42.6%, p=0.0028). In totality, glycemic control (A1C, TIR, A1C &amp;lt;7% without hypoglycemia) was significantly improved by once-weekly icodec vs daily glargine U100 with low rates of hypoglycemia in both arms. Disclosure J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, Inc. S.C.Bain: Advisory Panel; Novo Nordisk, Sanofi, Lilly, Boehringer Ingelheim Inc., AstraZeneca. A.Gowda: Employee; Novo Nordisk A/S. H.Horio: Employee; Novo Nordisk. E.Jodar: Other Relationship; Amgen Inc., AstraZeneca, Eli Lilly and Company, FAES, Novo Nordisk, UCB, Inc., Speaker's Bureau; Merck &amp; Co., Inc., Asofarma, ZP Pharmaceuticals. L.Lang lehrskov: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp &amp; Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. R.Trevisan: Advisory Panel; Novo Nordisk, AstraZeneca, Eli Lilly and Company, Other Relationship; Boehringer Ingelheim Inc., Sanofi. O.Mosenzon: Advisory Panel; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Bayer Inc., Employee; BOL Pharma, Research Support; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Speaker's Bureau; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Sanofi. Funding Novo Nordisk A/S

1809-PUB: Painful Diabetic Neuropathy—Patients Treated with High-Frequency (10 kHz) Spinal Cord Stimulation (SCS) Experience Significant Reductions in A1C and Weight

Objective: Up to 9 million Americans have painful diabetic neuropathy (PDN), which can be debilitating. For PDN patients, 10 kHz SCS has been shown to provide mean pain relief of 77% at 24 months (24M), and here we report secondary, novel potential benefits for A1C and body weight. Methods: Subjects received a 10 kHz SCS implant plus medical management for their pain and diabetes. Subjects were followed for 24M post-implantation. Key inclusion criteria were: PDN ≥12M refractory to medications, lower limb pain ≥5cm (10cm VAS), and A1C ≤10%. For T2D subjects, changes in weight were evaluated for all subjects and cohorts with pre-implant BMI ≥30 and ≥35, and changes in A1C were evaluated for cohorts with pre-implant A1C ≥7.0% and ≥8.0%. Results: For cohorts evaluated, A1C and weight generally decreased with time (Fig. 1). For subjects with pre-implant A1C ≥8.0%, the mean A1C reduction was 0.52% at 6M (p=0.064) and 1.04% at 24M (p=0.007). For all subjects, the mean weight reduction was 1.8 kg at 12M (p=0.058) and 3.1 kg at 24M (p=0.003). For subjects with pre-implant BMI ≥35, the mean weight reduction was 5.4 kg at 24M (p=0.005). Conclusions: Previously reported pain relief and sensory improvement, coupled with reductions in A1C and weight reported here, further demonstrate the benefits of 10 kHz SCS treatment in the comprehensive care of T2D patients with PDN. Disclosure D.C.Klonoff: Consultant; EOFlow Co., Ltd., Fractyl Health, Inc., Integrity, Lifecare, Inc., Rockley Photonics, Thirdwayv Inc. B.L.Levy: Advisory Panel; Nevro Corp., CeQur SA, Consultant; Nevro Corp., CeQur SA, Digma Medical. M.Jaasma: Consultant; Bone Health Technologies, Inc., Employee; Nevro Corp., Bone Health Technologies, Inc. M.Bharara: Employee; Nevro Corp. C.E.Nasr: Advisory Panel; Siemens, Horizon Therapeutics plc. D.L.Caraway: Employee; Nevro Corp. E.Petersen: Consultant; Abbott, Biotronik, Medtronic, Nalu, Nevro Corp., Presidio Medical, Saluda Medical, Vertos Medical Inc., Research Support; Nalu, Nevro Corp. D.G.Armstrong: Research Support; Medaxis LLC. Funding Nevro Corp.

Evaluation of outpatient health services in diabetes mellitus in a middle-income setting: a retrospective cohort study involving secondary care

In Brazil, it is necessary to assess the different levels of health care in diabetes mellitus (DM) in order to integrate them. In this retrospective cohort study, we analyzed 1,122 medical records of patients with DM from specialized services with interdisciplinary health teams (IHT) in the city of Ourinhos, São Paulo state, Brazil, to assess the impact of secondary care on glycemic control in patients with DM in those places and to compare baseline and follow-up DM care indicators concerning clinical evaluation and drug treatment regimens in the aforementioned health services. The study covered consultations carried out from September/2013 to September/2017. Data were collected from initial and final appointments in medical records and revealed an increase of 31.21% in insulin introduction and of 73.53% in regimens with three or more non-insulin antidiabetic (NIA) medications. Among the 570 patients with at least two glycated hemoglobin (A1C) measurements in the aforementioned review, 146 did not require any therapeutic adjustment between initial and final appointments, 123 required a subtle adjustment, 95, a moderate adjustment, and 206, an intense adjustment. There was a noticeably higher A1C reduction between initial and final appointments when patients who required an intense drug adjustment were compared to those who did not need any different NIA drug (p-value &lt; 0.0001). In addition to optimizing drug treatment, essential exams in DM were performed with higher frequency, with an increase of 63% in ophthalmology evaluation performed during secondary care approach and 60.65% more individuals being screened for diabetic chronic kidney disease. IHT secondary care considered in this study, therefore, not only improved glycemic control of patients with DM, especially by optimization of NIA regimens and timely prescription of insulin, but also increased the screening for microvascular complications.

178-OR: Better Glycemic Control with Once-Weekly Insulin Icodec vs. Once-Daily Insulin Degludec in Insulin-Naïve Type 2 Diabetes (ONWARDS 3)

Efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin degludec (degludec) in insulin-naïve adults with T2D were examined in ONWARDS 3 (NCT04795531), a 26-week, randomized, double blind, double dummy, treat-to-target, phase 3a trial. Participants (n=588) were randomized 1:1 to icodec or degludec. Key outcomes are shown in the table. The primary endpoint was A1C change from baseline (BL) to week 26. Estimated mean A1C change was greater with icodec (−1.57%; BL: 8.55%) vs degludec (−1.36%; BL: 8.48%); estimated treatment difference −0.21%-points (95% CI −0.34, −0.08), confirming non-inferiority (p&amp;lt;0.0001) and superiority (p=0.0016). Level 2 or 3 hypoglycemia rates were numerically but not statistically significantly higher with icodec vs degludec in the on-treatment period. Odds of achieving A1C &amp;lt;7% without level 2 or 3 hypoglycemia were statistically significantly higher with icodec vs degludec. There were no significant differences in weekly insulin dose from week 24 to 26 or body weight change from BL to week 26 between arms. No unexpected safety findings were observed. Overall, once-weekly icodec demonstrated superior A1C reduction vs once-daily degludec with low level 2 or 3 hypoglycemia rates in both arms. Icodec may facilitate insulin treatment acceptance and adherence by reducing basal insulin injections from ≥365 to 52 per year. Disclosure I.Lingvay: Advisory Panel; Novo Nordisk A/S, Lilly Diabetes, Boehringer-Ingelheim, Sanofi, Consultant; Carmot Therapeutics, Inc., Merck Sharp &amp; Dohme Corp., Janssen Scientific Affairs, LLC, Pfizer Inc., Intercept, Intarcia, Valeritas, TargetRWE, Shionogi, Zealand Pharma, Structure, Bayer, Research Support; Novo Nordisk A/S, Boehringer-Ingelheim. M.Asong: Employee; Novo Nordisk. C.Desouza: Advisory Panel; Novo Nordisk A/S, Bayer Inc., Consultant; Asahi Kasei Corporation, Research Support; Eli Lilly and Company. P.Gourdy: Advisory Panel; Novo Nordisk, Eli Lilly and Company, Sanofi, Bayer Inc., Merck Sharp &amp; Dohme Corp., Novartis, Intercept Pharmaceuticals, Inc., Research Support; Novo Nordisk, Speaker's Bureau; Novo Nordisk, Eli Lilly and Company, Sanofi, Abbott, AstraZeneca, Boehringer-Ingelheim. S.Kar: None. A.G.Vianna: Advisory Panel; AstraZeneca, Board Member; Abbott Diabetes, Novo Nordisk, Medtronic, Research Support; Novo Nordisk, Anji Pharmaceuticals, Lilly, Speaker's Bureau; AstraZeneca, Novo Nordisk, Medtronic. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. S.M.Vinther: Employee; Novo Nordisk. Y.Mu: Speaker's Bureau; Abbott Diabetes, Boehringer Ingelheim Inc., Novo Nordisk (China), Sanifit. Funding Novo Nordisk A/S

837-P: Improved Outcomes across Socioeconomically Advantaged and Disadvantaged Communities—A Real-World Study

Socioeconomic conditions of one's community have been attributed to disparities in diabetes outcomes and management practices. Among a random sample (n=19955) of people with type 2 diabetes receiving care at a nationwide telemedicine clinic utilizing a carbohydrate restricted nutritional approach and continuous remote care model (CR-CRCM), we explored A1c and medication utilization by area deprivation index quintile (Q). Upon enrollment, patients residing in more disadvantaged areas (Q4, Q5) had higher A1c compared to the least disadvantaged area (Q1; 7.8% vs 7.7%, p&amp;lt;0.01), and insulin (INS) and sulfonylureas (SU), but not other medication classes, were prescribed to a greater proportion of patients living in Q5 (25% INS, 23% SU) compared to Q1 (18% INS, 18% SU) and Q2 (21% INS, 19% SU) after accounting for differences in age, sex, baseline BMI, baseline INS use (when appropriate), and race and ethnicity (p&amp;lt;0.05). After one year in clinic, no differences in the prescription of medication classes between Q were observed, except for INS, where greater use remained only in Q5 than Q1 (14% vs 10%, p=0.011); among those remaining on INS, dose was reduced by 49-58% across all Q (p&amp;lt;0.001). Differences in SU use were no longer present; 77-83% fewer SU were prescribed across Q. Differences in A1c between Q4 (6.6%) and Q5 (6.7%) vs Q1 (6.5%) remained (p&amp;lt;0.001), though all groups achieved significant reductions in A1c of 1.1-1.2% (all p&amp;lt;0.001) concurrent with reduced prescription of all diabetes medication (from 1.7-1.8 to 1.1-1.2 medication classes per person). Across all levels of socioeconomic disadvantage, patients achieved clinically and statistically meaningful reductions in A1c and medication. Higher rates of SU use among patients residing in more disadvantaged areas were mitigated through a CR-CRCM to improve glycemia. Further, these data suggest a CR-CRCM may overcome financial barriers to optimal diabetes management through reduced need for medication. Disclosure A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp.