Effect Of Semaglutide Research Articles

FRI-469 - Prevalence of, and effect of semaglutide on, features of non-alcoholic steatohepatitis in patients with obesity with and without type 2 diabetes: analysis of data from two randomised placebo-controlled trials using SomaSignal tests

FRI-469 - Prevalence of, and effect of semaglutide on, features of non-alcoholic steatohepatitis in patients with obesity with and without type 2 diabetes: analysis of data from two randomised placebo-controlled trials using SomaSignal tests

THE EFFECT OF SEMAGLUTIDE ON BLOOD PRESSURE IN PATIENTS WITHOUT DIABETES: A SYSTEMATIC REVIEW AND META-ANALYSIS

Objective: The interplay of hypertension and obesity is well described. Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). The aim of this review is to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. Design and method: This systematic review was performed in line with the 2020 PRISMA statement. Relevant studies were identified via a search of MEDLINE, EMBASE, Cochrane Library, CINAHL and Web of Science. Studies were screened to include randomised controlled trials of semaglutide versus a placebo in adults without diabetes. Continuation of anti-hypertensive treatment was a secondary outcome. Pooled and sensitivity analyses were performed and risk of bias was assessed. Results: 611 potential studies were found by the search and 6 RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in SBP was -4.83 mmHg (95% CI -5.65 to -4.02) while that for DBP was -2.45 mmHg (95% CI -3.65 to -1.24). Only two studies (STEP 1, 4) reported change in anti-hypertensive medications. In STEP 1, 34.3% of those on anti-hypertensive medications, and receiving the intervention, either decreased or stopped these drugs, versus 16% in the placebo group. Equivalent figures were 25.5% and 11.9% for STEP 4. Critical appraisal revealed all included studies to be of a high methodological quality. Conclusions: The magnitude of BP reduction evident following semaglutide treatment in normotensive populations with obesity and without diabetes is clinically significant. The effect of semaglutide in those with obesity and hypertension is yet to be determined. Targeting excess body weight may be a novel therapeutic strategy for patients with difficult to control hypertension.

Effect of semaglutide on weight, hba1c and liver enzymes in type 2 diabetes patients

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effects of Semaglutide on Metabolic Syndrome Parameters in Non-Diabetics: A Meta-analysis of Randomized Controlled Trials

Effects of Semaglutide on Metabolic Syndrome Parameters in Non-Diabetics: A Meta-analysis of Randomized Controlled Trials

Effects of semaglutide and empagliflozin on oxygenation, vascular autoregulation, and central thickness of the retina in people with type 2 diabetes: A prespecified secondary analysis of a randomised clinical trial

AimsSemaglutide and empagliflozin have shown cardiovascular protection. In SUSTAIN-6, semaglutide was associated with an increased risk of diabetic retinopathy. We investigated whether changes in retinal oxygenation, retinal vascular autoregulation, and central retinal thickness are altered by semaglutide, empagliflozin or the combination. MethodsThis study was a prespecified, secondary outcome from a randomised, 32 weeks partly placebo-controlled, partly open-label, clinical trial on the effects of semaglutide and empagliflozin on arterial stiffness and kidney oxygenation. A total of 120 participants with type 2 diabetes, established or high risk of cardiovascular disease and age ≥50 years were randomised into four parallel groups (semaglutide, empagliflozin, the combination or tablet placebo, n = 30 for each group). We primarily hypothesized that semaglutide would increase venular oxygenation. ResultsWe found no changes in retinal arteriolar, venular or venular-arteriolar oxygenation nor in retinal vessel diameter regardless of treatment group.Semaglutide increased central retinal thickness compared to placebo with ~1 % (3.8 μm 95 % CI [0.9;6.7], p = 0.009) with no changes in the empagliflozin or combination group. ConclusionNeither semaglutide, empagliflozin nor the combination alters markers of retinal function. The effect of semaglutide on central retinal thickness was small, but the clinical significance is uncertain.

Current and emerging medications for the management of obesity in adults.

Current and emerging medications for the management of obesity in adults.

Effects of Semaglutide and Empagliflozin on Inflammatory Markers in Patients with Type 2 Diabetes.

Low-grade inflammation is associated with complications of type 2 diabetes. Glucagon-like peptide-1 receptor agonists and sodium-glucose transporter-2 inhibitors have shown cardioprotective effects that are independent of their glucose-lowering effects. Cardio-protection could be mediated by the anti-inflammatory effects of these medications, but there is currently limited evidence to support this hypothesis. We conducted a prospective clinical study in patients with type 2 diabetes requiring treatment intensification. Ten patients were assigned to receive empagliflozin 10 mg and 10 patients to receive s/c semaglutide (titrated to 1 mg once a week) in a non-randomised manner. All parameters were measured at baseline and after 3 months. Fasting plasma glucose and glycated haemoglobin improved significantly in both treatment groups, with no between-group differences. Body weight and body mass index reduced significantly more in the semaglutide group, whereas waist circumference decreased only in the empagliflozin group. There was a trend for high-sensitivity CRP reduction in both treatment groups that did not reach statistical significance. Interleukin-6 and the neutrophil-to-lymphocyte ratio did not change in either group. Ferritin and uric acid decreased significantly only in the empagliflozin group, and ceruloplasmin decreased significantly only in the semaglutide group. Though there were clinically meaningful improvements in diabetes control in both treatment arms, we could detect only minor changes in some inflammatory markers.

Two-year effect of semaglutide 2.4mg on control of eating in adults with overweight/obesity: STEP 5.

This study evaluatedthe effect of once-weekly semaglutide 2.4mg on 2-year control of eating. In STEP 5, adults with overweight/obesity were randomized 1:1 to semaglutide 2.4mg or placebo, plus lifestyle modification, for 104 weeks. A 19-item Control of Eating Questionnaire was administered at weeks 0, 20, 52, and 104 in a subgroup of participants. P values were not controlled for multiplicity. In participants completing the Control of Eating Questionnaire (semaglutide, n=88; placebo, n=86), mean body weight changes were -14.8% (semaglutide) and -2.4% (placebo). Scores significantly improved with semaglutide versus placebo for Craving Control and Craving for Savory domains at weeks 20, 52, and 104 (p < 0.01); for Positive Mood and Craving for Sweet domains at weeks 20 and 52 (p < 0.05); and for hunger and fullness at week 20 (p < 0.001). Improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 with semaglutide. At 104 weeks, scores for desire to eat salty and spicy food, cravings for dairy and starchy foods, difficulty in resisting cravings, and control of eating were significantly reduced with semaglutide versus placebo (all p < 0.05). In adults with overweight/obesity, semaglutide 2.4mg improved short- and longer-term control of eating associated with substantial weight loss.

The Effect of Semaglutide on Blood Pressure in Patients without Diabetes: A Systematic Review and Meta-Analysis.

(1) Background: Recent advances in the pharmacological treatment of obesity with glucagon-like peptide-1 receptor agonists (GLP-1 RA) highlight the potential to target excess body weight to improve blood pressure (BP). This review aimed to determine the BP reduction in trials of semaglutide for weight reduction in patients without diabetes. (2) Methods: Relevant studies were identified via a search of research databases. Studies were screened to include randomized controlled trials (RCTs) of semaglutide versus a placebo in adults. Pooled and sensitivity analyses were performed, and risk of bias was assessed. (3) Results: six RCTs, with 4744 participants, were included in the final analysis. At baseline, the cohorts in these studies had a mean BP in the normotensive range. The mean difference in systolic BP was -4.83 mmHg (95% CI: -5.65 to -4.02), while that for diastolic BP was -2.45 mmHg (95% CI: -3.65 to -1.24). All included studies were of a high methodological quality. (4) Conclusions: A clinically significant reduction in BP was evident following semaglutide treatment in normotensive populations without diabetes. The effect of semaglutide in those with obesity and hypertension is as yet undetermined. Targeting excess body weight may be a novel therapeutic strategy for these patients.

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity

AimThis work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments. MethodsThis study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. ResultsThe sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m2 and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. ConclusionThese results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options.

Semaglutide treatment for obesity in teenagers: a plain language summary of the STEP TEENS research study.

What is this summary about? This is a plain language summary of the STEP TEENS research study, which was originally published in the New England Journal of Medicine. As more teenagers are living with obesity than ever before, researchers are searching for new treatments. This was the first study looking at how well the medicine semaglutide works as a treatment for obesity in teenagers. What were the results? In this study, researchers looked at the effect of semaglutide on body mass index (BMI) and weight loss compared to a dummy medicine (placebo). A 17% decrease in BMI was reported for teenagers treated with semaglutide compared with placebo. For weight loss, an 18 kg decrease was seen when comparing semaglutide with placebo. Researchers found that there were more teenagers who had weight loss of 5%, 10%, 15%, and 20% or more in the group given semaglutide compared with the group given placebo. Improvements were also seen with semaglutide treatment for some risk factors for other diseases caused by obesity. Semaglutide was generally well tolerated by the teenagers with obesity in this study, and serious medication side effects did not happen very often. What do the results mean? The results from this study showed that there were no safety issues with semaglutide in teenagers with obesity, and that semaglutide can be used to help them lose weight. Clinical Trial Registration: NCT04102189 (ClinicalTrials.gov).

Evoke and evoke+: design of two large‐scale, double‐blind, placebo‐controlled, phase 3 studies evaluating the neuroprotective effects of semaglutide in early Alzheimer’s disease

AbstractBackgroundPreclinical, clinical, and real‐world evidence suggest benefits in Alzheimer’s disease (AD)‐related symptoms and reduced risk of dementia in type 2 diabetes following treatment with glucagon‐like peptide 1 receptor agonists (GLP‐1RA; Figure 1). The phase 3 evoke and evoke+ trials (NCT04777396 and NCT04777409, respectively) will assess the efficacy and safety of the oral GLP‐1RA semaglutide versus placebo in participants with early AD. Here, we present the design of these trials.Methodevoke and evoke+ are two randomized, double‐blind, placebo‐controlled trials (Figure 2) recruiting across 38 countries, with 2 further countries pending (Figure 3). In each trial, a planned 1,840 amyloid‐positive participants (aged 55 to 85 years) with mild cognitive impairment (MCI) due to AD (Clinical Dementia Rating [CDR] global = 0.5) or mild AD dementia (CDR global = 1.0) will be randomized (1:1) to oral semaglutide 14 mg once‐daily (escalated via 3‐ and 7‐mg doses over 8 weeks) or placebo for 156 weeks. Participants may use approved AD treatments if on a stable dose ≥3 months before screening. Other key inclusion criteria are: Mini‐Mental State Examination score ≥22 and Repeatable Battery for the Assessment of Neuropsychological Status delayed memory index score ≤85. The key difference between the trials is the inclusion of ≥20% of participants with significant small vessel co‐pathology in evoke+. The primary endpoint is change in the CDR – Sum of Boxes score from baseline to week 104. Confirmatory secondary endpoints are change in Alzheimer’s Disease Cooperative Study‐Activities of Daily Living‐MCI score, and time to progression to dementia among participants with MCI at baseline. Exploratory endpoints include effects on neurodegeneration and neuroinflammation assessed by changes in plasma and cerebrospinal fluid biomarkers. After week 104, participants will continue their original randomized, double‐blind, placebo‐controlled treatment for a 52‐week extension phase followed by a 5‐week follow‐up, allowing assessment of the long‐term effects of semaglutide. A full list of endpoints is provided in Figure 4.ResultThe evoke and evoke+ read‐outs are expected in 2025.Conclusionevoke and evoke+ will be the first large‐scale phase 3 trials (Ntotal = 3,680) to investigate the hypothesized neuroprotective disease‐modifying effect of semaglutide in early AD.

Effects of semaglutide on vascular structure and proteomics in high-fat diet-induced obese mice.

Obesity is a chronic metabolic disease caused by a combination of genetic and environmental factors. To determine whether semaglutide could improve aortic injury in obese C57BL/6J mice, and further explore its molecular mechanism of action using proteomics. 24 C57BL/6J male mice were randomly divided into normal diet group (NCD group), high-fat diet group (HFD group) and high-fat diet + semaglutide group (Sema group, semaglutide (30 nmol/kg/d) for 12 weeks). The serum samples were collected from mice to detect blood glucose, insulin and blood lipid concentrations. Aortic stiffness was detected by Doppler pulse wave velocity (PWV). Changes in vascular structure were detected by HE, masson, EVG staining and electron microscopy. The aorta-related protein expression profiles were detected by proteomic techniques, and proteins with potential molecular mechanisms were identified. Semaglutide could reduce body weight, the concentrations of blood glucose, total cholesterol (TC), triglycerides (TG), lipoprotein cholesterol (LDL-C), and reduce the aortic PWV and ameliorate vascular damage in obese mice. The results of proteomic analysis showed there were 537 up-regulated differentially expressed proteins (DEPs) and 322 down-regulated DEPs in NCD/HFD group, 251 up-regulated DEPs and 237 down-regulated proteins in HFD/Sema group. There were a total of 25 meaningful overlapping DEPs in the NCD/HFD and HFD/Sema groups. GO enrichment analysis of overlapping DEPs found that these differential proteins were mainly located in the signaling pathways of the extracellular matrix. The most obvious changes of extracellular matrix associated proteins in the three experimental groups were Coll5a1, Lama4, Sparc. Semaglutide may protect vascular structure and improve endothelial permeability by reducing the levels of Coll5a1, Lama4, Sparc in extracellular matrix, so as to improve vascular function and achieve vascular protection.

The Effect of Semaglutide on Kidney Function: Post Hoc Analysis of Three Randomized Controlled Trials in Non-Alcoholic Fatty Liver Disease

The Effect of Semaglutide on Kidney Function: Post Hoc Analysis of Three Randomized Controlled Trials in Non-Alcoholic Fatty Liver Disease

Effect of semaglutide on lipoprotein subfractions and chemerin levels in type 2 diabetic patients

Background and Aims : There are strong associations between obesity, cardiovascular complications, and lipid abnormalities in type 2 diabetes (T2DM). Once-weekly administration of semaglutide lowers the blood glucose level in a glucose-dependent manner and has a beneficial effect on lipid levels. Small and dense LDL particles play a pivotal role in the development of atherosclerosis and cardiovascular diseases. Chemerin, a previously described adipokine, is associated with insulin resistance associated with obesity and lipoprotein abnormalities.

Effects of semaglutide on cardiovascular risk factors and eating behaviors in type 2 diabetes

AimsAim of the present study was to evaluate the impact of once-weekly semaglutide on different end-points indicative of metabolic control, cardiovascular risk, dietary behavior, and treatment satisfaction in T2DM.MethodsThis was a retrospective observational study conducted in a diabetes clinic. Changes in HbA1c, fasting blood glucose (FBG), weight, blood pressure, lipid profile, and number of antihypertensive drugs at 32 weeks (T1) after the first prescription of semaglutide (T0) were analyzed. Furthermore, at T1 patients were asked to fill-in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Control of Eating Questionnaire (COEQ).ResultsOverall, 104 patients were identified (mean age 63.6 ± 10.4 years, 58.7% men, diabetes duration 12.7 ± 8.7 years). After 32 weeks of treatment with semaglutide, HbA1c levels were reduced by 1.38%, FBG by − 56.53 mg/dl, weight by 6.03 kg. Systolic and diastolic blood pressure, total, HDL-, LDL-, and non –HDL cholesterol, and triglycerides significantly improved. The number of glucose-lowering and antihypertensive drugs also decreased. At T1, DTSQ score was 32.23 ± 1.44, whereas COEQ indicated low levels of hunger and good control of eating.ConclusionsThe study documented benefits of semaglutide on metabolic control and multiple CV risk factors, simplification of therapeutic schemes and high satisfaction with diabetes treatment, and eating behaviors indicative of healthy diet and reduced food intake.

Population pharmacokinetic of paracetamol and atorvastatin with co-administration of semaglutide.

Semaglutide is a glucagon‐like‐peptide‐1 (GLP‐1) analogue marketed for once‐weekly subcutaneous administration for type 2 diabetes mellitus. Like other long‐acting GLP‐1 analogues, semaglutide reduces gastric emptying and, potentially, alters the rate of absorption of orally co‐administered drugs. The objective of the current analysis was to evaluate the effects on the gastric emptying rate caused by semaglutide on pharmacokinetic model parameters of paracetamol and atorvastatin in healthy subjects. Non‐linear mixed effect modeling was used to estimate population pharmacokinetic model parameters of paracetamol and atorvastatin after single doses with or without semaglutide. The absorption rate (ka) of paracetamol decreased by 53% when co‐administered with semaglutide. For atorvastatin, ka and transit compartment rate (ktr) decreased by 72% and 91%, respectively. Thus, gastric emptying, measured as T50, i.e., drug disappearance from the absorption compartments, showed an additional 5‐min delay for paracetamol and a 67‐min delay for atorvastatin when co‐administered with semaglutide. Semaglutide affected pharmacokinetic model parameters of paracetamol and atorvastatin, and minor quantitative differences in gastric emptying between placebo vs. semaglutide administration were observed. However, these effects of semaglutide were considered not to be of clinical relevance.

756-P: The Effect of Semaglutide on Alanine Aminotransferase (ALT) Levels: Results from the Association of British Clinical Diabetologists (ABCD) Audit

Obesity and type 2 diabetes are important drivers for the development of nonalcoholic fatty liver disease (NAFLD) . Glucagon-like peptide-1 receptor agonists (GLP1RAs) are efficacious for these conditions, but their potential as treatments for NAFLD remains unclear. As serum ALT concentration is routinely measured in clinical care, we evaluated the impact of the GLP1RA, semaglutide, on ALT in those at risk of NAFLD. Methods: Data submitted to the ABCD semaglutide audit (launched in 2019) were analysed. Change in ALT from baseline was assessed and corrected for change in covariates and concomitant medications using a multiple linear regression in Stata 16 . Baseline ALT levels were used to perform a stratified analysis as follows: normal (ALT 0-29U/L) , mildly elevated (30-59 U/L) and significantly elevated (≥60U/L) . Missing data were multiply imputed. Results: Data for 1,623 individuals (50.2% men) were included with baseline (mean±SD) : age 58.9±11.0 years, HbA1c9.4±1.7%, weight 104.6±2.8kg, BMI 37.1±7.4kg/m2 and median (IQR) diabetes duration 10.9 years (6-15.4) and ALT 26U/L (19-36) . Median (IQR) follow-up was 8.2 months (5-12) . At follow-up, changes in HbA1c and weight were -1.2% (95%CI -1.0, -1.3; p&amp;lt;0.001) and -2.4kg (95%CI -1.7, -3.1; p&amp;lt;0.001) respectively. No significant change in ALT was seen across the entire cohort (p=0.172) . However, ALT rose in the normal group (+14.6U/L; 95%CI 10.4, 18.8; p&amp;lt;0.001) and fell in the significantly elevated group (-16.2U/L; 95%CI -11.8, -20.5; p&amp;lt;0.001) . No change was noted in the mildly elevated group (p=0.33) . The differences between groups were statistically significant (p&amp;lt;0.0001) . Conclusion: Among patients with significantly raised ALT, semaglutide was associated with ALT reduction, but this finding may result from regression to the mean. Measurement in parallel of further biomarkers of liver fibrosis will be required to assess the potential of semaglutide as a NAFLD therapy. Disclosure T.S.J. Crabtree: Other Relationship; Abbott Diabetes, Novo Nordisk, Sanofi. D.K. Sennik: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi. D. Barnes: None. S. Sivappriyan: None. K. Adamson: None. S.M. Phillips: None. A. Evans: None. N. Larsen: None. A. Panesar: None. I.W. Gallen: None. I.R. Idris: None. R.E. Ryder: None. Funding The ABCD audit is support by an unrestricted grant from NovoNordisk

1413-P: Semaglutide 2.4 mg Improved Glucose Metabolism and Reverted Prediabetes to Normoglycemia in Adults with Overweight/Obesity vs. Liraglutide 3.0 mg (STEP 8)

The STEP 8 trial randomized 338 adults with overweight/obesity to weekly semaglutide 2.4 mg or placebo (PBO) , or daily liraglutide 3.0 mg or PBO, plus lifestyle intervention for 68 wks (3:1:3:1) ; PBO data not shown. Body weight (BW) change was greater with semaglutide vs. liraglutide (-15.8% vs. -6.4%, respectively; p&amp;lt;0.0001) . This exploratory analysis assessed effects on glucose metabolism and glycemic status (normoglycemia; prediabetes; T2D) at wk 68 in participants (pts) with prediabetes at baseline (BL; 43 semaglutide/45 liraglutide; mean HbA1c 5.9/5.8%; fasting plasma glucose [FPG] 102/100 mg/dL; HOMA-IR 4.9/3.7; BW 104/1kg) . Analyses were not adjusted for multiplicity. At wk 68, 89.5% of pts were normoglycemic with semaglutide vs. 64.9% with liraglutide (p=0.01) (Figure) ; in these pts, 76.5% had weight loss ≥10% with semaglutide vs. 33.3% with liraglutide. One pt in each group developed T2D (Figure) . From BL to wk 68, semaglutide led to greater reductions vs. liraglutide in HbA1c (difference: -0.22 %; p=0.0002) , FPG (difference: -6.2 mg/dL; p=0.02) , and HOMA-IR (relative % difference: -28%; p=0.02) . In conclusion, both semaglutide 2.4 mg and liraglutide 3.0 mg had clinically beneficial effects on glucose metabolism and glycemic status in pts with overweight/obesity and prediabetes, though the effect of semaglutide was greater vs. liraglutide. Disclosure J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck &amp; Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. W.Garvey: Other Relationship; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Epitomee, JAZZ Pharmaceuticals, Novo Nordisk, Novo Nordisk, Pfizer Inc., Pfizer Inc. B.Goldman: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. U.Khalid: None. R.Sørrig: Employee; Novo Nordisk A/S. D.Rubino: Advisory Panel; Novo Nordisk, Other Relationship; Endocrine Society, PeerView, WebMD LLC, Research Support; Boehringer Ingelheim International GmbH, Novo Nordisk, Obesinov, SARL, Speaker's Bureau; Novo Nordisk, Stock/Shareholder; Novo Nordisk. Funding Funded by Novo Nordisk A/S

752-P: Study Design and Baseline Profile for Patients with Type 2 Diabetes in the Semaglutide Once-Weekly Randomized Pragmatic Trial (SEPRA)

SEPRA (NCT03596450) is a 2-yr, multicenter, open-label, randomized pragmatic clinical trial comparing the long-term effects of once-weekly subcutaneous semaglutide vs. standard of care (both added to ≤2 oral antidiabetic medications) in US health-insured adults with T2D and physician-determined inadequate glycemic control. SEPRA will assess glycemic control, weight loss, healthcare utilization, and patient-reported outcomes by collecting individual-level data from routine clinical practice and health insurance claims. The primary endpoint is the proportion of patients achieving HbA1c &amp;lt;7.0% at yr 1. The study design was evaluated using the Pragmatic Explanatory Continuum Indicator Summary (PRECIS) -2 assessment; it scored 4-5 in all 9 domains, suggesting a highly pragmatic study. Of 1,278 patients enrolled, 54% were male with mean (± SD) age 57.4 ± 11.1 yrs, BMI 35.7± 8.0 kg/m2, diabetes duration 7.4 ± 6.0 yrs, HbA1c 8.48 ± 1.6%, and mean individualized HbA1c target 6.66 ± 0.5%. Of note, 86.9% of patients had HbA1c &amp;gt;7.0% and most required sizeable reductions in HbA1c to reach the clinician-assigned individualized target. SEPRA will provide real-world evidence on the long-term effectiveness of semaglutide in a population with a broad range of HbA1c levels and other clinical characteristics when used as intensification early on in usual T2D care practice settings. Disclosure V.Willey: Employee; HealthCore Inc. J.B.Buse: Consultant; Alkahest, Anji, AstraZeneca, Boehringer Ingelheim International GmbH, Cirius Therapeutics, Inc., Eli Lilly and Company, Fortress biotech, GentiBio, Glycadia, Glyscend, Janssen Pharmaceuticals, Inc., Mellitus Health, Moderna, Inc., Pendulum Therapeutics, Praetego, LLC, Stability Health, Valo, Zealand Pharma A/S, Other Relationship; Adocia, AstraZeneca, Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics, Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, vTv Therapeutics, Stock/Shareholder; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. B.Harty: None. J.L.Mitchell: None. B.P.Soule: Employee; Bristol-Myers Squibb Company, Novo Nordisk. H.N.Christensen: Employee; Novo Nordisk. M.J.Cziraky: None. S.Skibsted: Employee; Novo Nordisk. Funding Funded by Novo Nordisk Inc