Oral Semaglutide Research Articles

Does a higher dose of oral semaglutide treatment make sense?

Does a higher dose of oral semaglutide treatment make sense?

Real-world clinical evidence of oral semaglutide on metabolic abnormalities in subjects with type 2 diabetes: a multicenter retrospective observational study (the Sapporo-Oral SEMA study).

Oral semaglutide has potent anti-hyperglycemic efficacy in phase III trials. However, the complicated dosing instructions hamper to use this drug; therefore, we evaluated the efficacy and safety of oral semaglutide in subjects with type 2 diabetes in a real-world clinical setting. In this multi-center retrospective observational study, we analyzed subjects with type 2 diabetes newly treated with an oral semaglutide for >6 months at four medical centers located in Sapporo, Japan. The changes in glycated hemoglobin, body weight, and other metabolic parameters were evaluated and any adverse event leading to semaglutide discontinuation were recorded from February 2021 to December 2022. This study was registered with the University Hospital Medical Information Network Center (UMIN000050583). Of 543 subjects who met the inclusion criteria, data for 434 subjects (age 55.5 ± 12.6 years; body mass index 29.6 ± 6.0 kg/m2) were analyzed. After a 6 months of observation period, semaglutide 3 mg, 7 mg, or 14 mg was used by 55 (12.7%), 241 (55.5%), and 138 (31.8%) of subjects, respectively. Both glycated hemoglobin and body weight significantly improved: 7.65 ± 1.11% to 6.88 ± 0.91% (p < 0.001) and 80.2 ± 19.2 kg to 77.6 ± 19.2 kg (p < 0.001), respectively. Efficacy was also confirmed in the subgroup switched from other anti-hyperglycemic agents, including dipeptidyl peptidase-4 inhibitors. In total, 154 subjects had symptomatic gastrointestinal symptoms and 39 (7.2%) were discontinued semaglutide due to the adverse events. None of the participants experienced severe hypoglycemic events. Oral semaglutide in subjects with type 2 diabetes improved glycemic control and body weight in a real-world clinical setting.

Management of Hypertension, Obesity, Lipids, and Diabetes with Glucagon-like Peptide 1 Receptor Agonists

Abstract Hyperglycemia is considered one of the main risk factors for the development of cardiovascular diseases, and the situation becomes worse if the condition is associated with uncontrolled hypertension, dyslipidemia, and overweight or obesity. Since the first glucagon-like peptide 1 receptor agonist (GLP-1RA) being approved in 2005 for type 2 diabetes, the class has successfully developed newer compounds with more pronounced effects on glycemic control and body weight; not to forget the oral peptide in a pill as well; oral semaglutide. To manage hypertension, obesity, lipids, and diabetes, it is ascertained that a holistic approach is required or the class with pleiotropic benefits to treat accompanying metabolic disturbances. Over the years, the place for GLP-1RA therapy has changed with most guidelines recommending GLP-1RA therapy in patients with established or high risk of cardiovascular disease independently of glycemia.

Efficacy and safety of semaglutide combined with metformin in treating T2DM with overweight or obesity: a systematic review and meta-analysis.

To evaluate the efficacy and safety of semaglutide combined with metformin in treating type 2 diabetes mellitus (T2DM) patients who are overweight or obese. We conducted a comprehensive search across multiple databases including Wanfang, CNKI, Chinese Biomedical Literature, VIP, Embase, PubMed, Cochrane Library, and Web of Science. Studies were screened to include randomized controlled trials (RCTs) comparing semaglutide combined with metformin versus metformin alone in T2DM patients with obesity or who are overweight. Primary outcomes included glycemic efficacy and body mass index (BMI). Secondary endpoints included pancreatic function, blood lipids, and incidence of adverse effects. Pooled and sensitivity analyses were performed, and risk of bias was assessed. Ten studies met the inclusion criteria, all involving oral semaglutide. Compared with placebo, semaglutide with metformin significantly reduced fasting blood glucose (SMD: -0.94; 95% CI: -1.53 to -0.35) and 2-hour postprandial glucose (SMD: -0.97; 95% CI: -1.44 to -1.50; P<0.0001). It also lowered HbA1c levels (SMD: -1.13; 95% CI: -1.85 to -0.42; P<0.001) and BMI (SMD: -1.08; 95% CI: -1.47 to -0.69). Improvements were also noted in HOMA-IR and blood lipid levels. However, there were no significant differences in the incidence of adverse reactions, such as hypoglycemia, gastrointestinal reactions, and dizziness and headache between the two groups (all P>0.05). Treatment with semaglutide combined with metformin significantly improved glycemic control, insulin resistance, weight, BMI, and lipid profiles in patients with T2DM who are overweight or obese.

Significant effect of decreased weight and HbA1c by oral semaglutide (Rybelsus) for Type 2 Diabetes (T2D) patient

Significant effect of decreased weight and HbA1c by oral semaglutide (Rybelsus) for Type 2 Diabetes (T2D) patient

A feasibility study of the combination of intranasal insulin with oral semaglutide for cognition in older adults with metabolic syndrome at high dementia risk- Study rationale and design

IntroductionWe present the rationale and design of a double-blind placebo-controlled feasibility trial combining intranasal insulin (INI) with semaglutide, a GLP-1 receptor agonist, to improve cognition in older adults with metabolic syndrome (MetS) and mild cognitive impairment (MCI). Since both INI and dulaglutide have beneficial effects on the cerebrovascular disease (CVD), we anticipate that improved CVD will underlie the hypothesized cognitive benefits. MethodsThis 12-months trial will include 80 older adults aged > 60 with MetS and MCI, randomized to 4 groups: INI/oral semaglutide, intranasal placebo/oral semaglutide, INI/oral placebo, and intranasal placebo/oral placebo. Feasibility of combining INI with semaglutide will be tested by examining the ease of use of INI (20IU, twice/day) with semaglutide (14 once daily), adherence, and safety profile are the efficacy of combination therapy on global cognition and neurobiological markers: cerebral blood flow, cerebral glucose utilization, white matter hyperintensities, Alzheimer’s related blood biomarkers and expression of insulin signaling proteins measured in brain-derived exosomes. Efficacy will be assessed for the intent-to-treat sample. DiscussionThis feasibility study is anticipated to provide the basis for a multi-center large-scale randomized clinical trial (RCT) of the cognitive benefits of the combination of INI with semaglutide in individuals enriched for CVD and at high dementia risk.

Effects of Oral Semaglutide on Renal Function in Diabetic Kidney Disease: A Short-term Clinical Study.

In the SUSTAIN-6 trial, semaglutide reduced the risk of worsening nephropathy in patients with type 2 diabetes. The objective of this retrospective study was to elucidate the effect and safety of oral semaglutide (Rybelsus®) in patients with diabetic kidney disease (DKD). Six patients with DKD received 3 mg/day semaglutide orally. The observation period was 9.0±5.0 months. Changes in estimated glomerular filtration rate (eGFR), urinary protein, fasting blood glucose, and hemoglobin A1c were studied from 6 months before the administration of oral semaglutide until 6 months after administration. The change in eGFR over the 6 months prior to semaglutide administration was -1.2±1.6 ml/min/1.73 m2, showing a trend for a decrease; although not statistically significant, the change at 6 months after oral semaglutide initiation showed improved eGFR (1-50.7±1.8 ml/min/1.73 m2). Proteinuria was not reduced after treatment with oral semaglutide. No significant adverse effects (including retinopathy) were observed in any patient during the study. Despite the small sample size and short observation period, oral semaglutide was found to be a relatively well-tolerated drug for patients with DKD.

Type 2 diabetes mellitus pharmacological remission with dapagliflozin plus oral semaglutide

Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor and semaglutide, a glucagon-like peptide 1 receptor agonist, have both demonstrated efficacy in glycemic control, reducing blood pressure, body weight, risk of renal and heart failure in type 2 diabetes mellitus. In this observational, real-world, study we aimed to investigate the efficacy of the combination therapy with those two agents over glycemic control. We thus obtained the data of 1335 patients with type 2 diabetes followed by 11 Diabetes centers in Lombardia, Italy. A group of 443 patients was treated with dapagliflozin alone, the other group of 892 patients was treated with the combination therapy of dapagliflozin plus oral semaglutide. We analyzed changes in glycated hemoglobin from baseline to 6 months of follow-up, as well as changes in fasting glycemia, body weight, body mass index, systolic and diastolic pressure, heart rate, creatinine, estimated glomerular filtration rate and albuminuria. Both groups of patients showed an improvement of glycometabolic control after 6 months of treatment; indeed, the treatment with dapagliflozin plus oral semaglutide showed a reduction of glycated hemoglobin of 1.2% as compared to the 0.5% reduction observed in the dapagliflozin alone group. Significant changes were observed in body mass index, fasting plasmatic glucose, blood pressure, total cholesterol, LDL and albumin to creatinine ratio, with a high rate (55%) of near-normalization of glycated hemoglobin. Our real world data confirmed the potential of the oral combination therapy dapagliflozin with semaglutide in inducing pharmacological remission of type 2 diabetes mellitus.

The effect of semaglutide on blood pressure in patients with type-2 diabetes: a systematic review and meta-analysis

ObjectiveTo evaluate the blood pressure (BP) lowering ability of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), in individuals with type-2 diabetes (T2D).MethodsRandomized controlled trials (RCTs) comparing subcutaneous or oral semaglutide with placebo or other antihyperglycemic agents (AHAs) in T2D patients were identified by searching PubMed, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library. These screened studies included the outcomes of interest: systolic and/or diastolic BP. Weighted mean differences (WMDs) and 95 % confidence intervals (CIs) were used to present the meta-analysis results. Pooled and sensitivity analyses were performed, and the risk of bias was evaluated.ResultsTwenty-nine RCTs with a total of 26985 participants were recruited in the final analysis. The WMD in change from baseline in systolic BP (SBP) of semaglutide versus placebo or other AHAs was −2.31 mmHg (95% CI: −3.11 to −1.51), while that for diastolic BP (DBP) was 0.09 mmHg (95% CI: −0.16 to 0.33). It also reduced glycated hemoglobin A1c (HbA1c) by 0.75% (95% CI: −0.92 to −0.58) and body weight loss by 2.80 kg (95% CI: −3.51 to −2.08). The reduction in SBP was similar for subcutaneous and oral administration of semaglutide, with −2.36 (95% CI: −3.38 to −1.35) and −2.50 (95% CI: −3.48 to −1.53), respectively.ConclusionsIn T2D, SBP decreased significantly in the semaglutide group compared with placebo or other active controls. According to the efficacy results from this meta-analysis, subcutaneous and oral semaglutide have similar SBP-reducing effects. Therefore, the treatment of T2D patients with subcutaneous semaglutide or oral preparations is beneficial for reducing SBP.

EE15 Cost-Effectiveness Analysis of Oral Semaglutide as the Second-Line and Third-Line Treatment for Type 2 Diabetes Patient

EE15 Cost-Effectiveness Analysis of Oral Semaglutide as the Second-Line and Third-Line Treatment for Type 2 Diabetes Patient

Newer pharmacological interventions directed at gut hormones for obesity.

The objective is to review the newer pharmacological interventions for obesity, specifically single, dual and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and glucagon. There are several approved single or dual incretin agonists which can be administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and other experimental dual or triple incretin agonists. Analogues of amylin, peptide YY and oxyntomodulin, as well as the combination of a GLP1R agonist and GIPR antagonist also are in development. Oral semaglutide (administered daily) is approved for type 2 diabetes mellitus and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying, which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP-1 receptor agonists (e.g., oral danuglipron) will be developed for treating obesity. These pharmacological agents are having significant impact on glycaemic control and obesity and on their co-morbidities.

Greater time spent with HbA1c less than 7.0% with oral semaglutide versus oral comparators: An exploratory analysis of the PIONEER studies.

To assess how long participants with type 2 diabetes spent with HbA1c less than 7.0% and how likely they were to maintain this targetwith oral semaglutide 7 mg versus sitagliptin 100 mg or oral semaglutide 14 mg versus empagliflozin 25 mg, sitagliptin 100 mg or subcutaneous liraglutide 1.8 mg. Analyses used on-treatment data without rescue medication for all randomized participants (semaglutide [approved maintenance doses], n = 1880; comparators [not including placebo], n = 1412). Duration of time with HbA1c less than 7.0% was calculated using an HbA1c time curve. A binary endpoint of achieving HbA1c less than 7.0% at weeks 26 (week 24 for PIONEER 7) and 52 of each trial (and week 78 for PIONEER 3) was analysed. Mean duration of time with HbA1c less than 7.0% was greater with oral semaglutide 7 mg versus sitagliptin in PIONEER 3 (27 vs. 22 weeks) and with oral semaglutide 14 mg versus empagliflozin and sitagliptin (27-34 vs. 19 vs. 22 weeks, respectively), and similar versus subcutaneous liraglutide. A greater proportion of participants achieved and maintained HbA1c less than 7.0% for more than 75% of the trial with oral semaglutide 14 mg versus oral comparators. The odds of achieving HbA1c less than 7.0% at weeks 24/26 and 52/78 were significantly greater with oral semaglutide 14 mg versus oral comparators or subcutaneous liraglutide, and with oral semaglutide 7 mg versus sitagliptin. Oral semaglutide 7 and 14 mg resulted in greater time spent with HbA1c less than 7.0%, and a greater likelihood of achieving and maintaining HbA1c less than 7.0% versus oral comparators.

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience.

To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world clinical practice setting. The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3-5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant. Twenty patients (11 male: 9 female; mean age, 59.9 ± 1.5 years; mean diabetes duration, 8.5 ± 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 ± 0.3% to 8.2 ± 0.2% and 7.8 ± 0.2%, respectively) and fasting plasma glucose (from 11.2 ± 0.5 mmol/L to 9.2 ± 0.7 mmol/L and 8.9 ± 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 ± 2.7 kg to 92.7 ± 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients. Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation.

Effect of Oral Semaglutide on Weight &amp; Cardiac Biomarkers In patients With Hypothyroidism Treated Using Liothyronine+Levothyroxine Combination Therapy

Effect of Oral Semaglutide on Weight &amp; Cardiac Biomarkers In patients With Hypothyroidism Treated Using Liothyronine+Levothyroxine Combination Therapy

Budget impact of introducing oral semaglutide to the public healthcare benefit package in Saudi Arabia

BackgroundThe Kingdom of Saudi Arabia (KSA) has embarked on a Health Sector Transformation Program as part of the Kingdom’s Vision 2030 initiatives with the facilitation of access to healthcare services for the millions in KSA with diabetes an essential part of the Program. Decision-making tools, such as budget impact models, are required to consider the addition of new medications like oral semaglutide that have multifaceted health benefits and address barriers related to therapeutic inertia to reduce diabetes-related complications.ObjectiveTo determine the financial impact of the introduction of oral semaglutide as a treatment option for people with type 2 diabetes mellitus (T2DM) in KSA.MethodsFrom the public payer’s perspective, the budget impact model estimates the costs before and after the introduction of oral semaglutide over a 5-year time horizon. The budget impact of introducing oral semaglutide (primary comparator) compared with three different classes of diabetes medicines: glucagon-like peptide-1 receptor agonists (GLP-1), sodium-glucose transport protein 2 inhibitors (SGLT 2i) and dipeptidyl peptidase 4 inhibitors (DDP-4i) have been calculated based on the projected market shares. The model includes the cost of care through the incorporation of health outcomes that have an impact on the national payer’s budget in Saudi Riyals (SAR).ResultsThe budget impact over the five-year time horizon indicates a medication cost increase (17,424,788 SAR), and cost offsets which include a difference in diabetes management costs (-3,625,287 SAR), CV complications costs (-810,733 SAR) and weight loss savings of 453,936 SAR. The cumulative total cost difference is 12,427,858 SAR (0.66%).ConclusionThe introduction of oral semaglutide 14 mg as a second-line treatment option after metformin is indicated as budget-neutral to slightly budget-inflating for the public pharmaceutical formulary of KSA. The price difference is offset by positive health outcomes and costs. This conclusion was confirmed through a probabilistic sensitivity analysis.

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care.

This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42% < 5years), and a minority (15.6%) had a history of cardiovascular events. Importantly, oral semaglutide was started in subjects with various disease durations and background therapies. Notably, its initiation was accompanied by de-prescription of sulfonylureas, pioglitazone, DPP-4 inhibitors, and insulin. Choice of oral semaglutide was influenced by patient profiles and ongoing glucose-lowering regimens. Factors such as younger age, higher HbA1c, and ongoing SGLT-2 inhibitor therapy drove the choice of oral semaglutide with the aim of improving glycemic control. Projected glycemic effectiveness analysis revealed that oral semaglutide could potentially lead HbA1c to target in > 60% of patients, and more often than sitagliptin or empagliflozin. The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management.

Effect of tirzepatide on glycaemic control and weight loss compared with other glucagon-like peptide-1 receptor agonists in Japanese patients with type 2 diabetes mellitus.

To compare the therapeutic effects of glucose-dependent insulinotropic polypeptide (GIP)/ glucagon-like peptide-1 receptor agonists (GLP-1RAs) or GLP-1RAs in Japanese patients with type 2 diabetes (T2D). We systematically searched PubMed, MEDLINE, EMBASE, and the Cochrane Library up to July 2023. Randomized controlled trials (RCTs) that compared GLP-1RAs or GIP/GLP-1RAs in Japanese patients with T2D were selected. A network meta-analysis was conducted to indirectly compare the treatments, focusing on efficacy in reducing glycated haemoglobin (HbA1c) levels and body weight (BW). A total of 18 RCTs were included in this analysis. Tirzepatide 15 mg showed the most significant reduction in HbA1c levels and BW compared with subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg (HbA1c: mean difference [95% confidence interval] -0.52 [-0.96; -0.08] and - 1.23 [-1.64; -0.81]; BW: -5.07 [-8.28; -1.86] and -6.84 [-8.97; -4.71], respectively). Subcutaneous semaglutide showed a superior reduction in HbA1c compared with oral semaglutide. Both subcutaneous and oral semaglutide were more effective than conventional GLP-1RAs, such as dulaglutide, liraglutide and lixisenatide. Among Japanese patients with T2D, tirzepatide showed the greatest effectiveness in reducing HbA1c levels and inducing weight loss. The study provides evidence to guide GLP-1RA treatment strategies in Japanese patients with T2D.

FRI652 Type 2 Diabetes Management: More GLP1 Agonists And Less Metformin?

Abstract Disclosure: F.J. Lopez Maldonado: None. R.A. Cota: None. Case presentation: A 41-year-old male patient with family history of T2DM in both parents and brother, personal history of mild alcohol consumption and a sedentary job (public accountant), and obesity since age 30 presented to the endocrinology clinic due to failure to lose weight after 1 year of treatment with a nutritionist. During his first visit, the was asymptomatic and had acanthosis nigricans, his blood pressure was measured at 142/92 mmHg, weight was 100.8 kg, waist circumference was 128 cm, and serum glucose was at 280 mg/dL with an HbA1c of 11.9%. Further laboratory tests showed elevated levels of triglycerides (310 mg/dL), LDL (139 mg/dL), AST (96 U/L), and ALT (65 U/L). Two days later, glucose and HbA1c were repeated with similar results. A liver ultrasound was ordered which revealed diffuse hyperechogenicity of the liver and severe fatty liver disease. The ASCVD risk score was 5.4%. The patient was diagnosed with T2DM, obesity, mixed dyslipidemia, and fatty liver disease. The patient received education, nutrition support, exercise, and pharmacotherapy management with stepped-dose oral semaglutide without metformin. The dose was increased monthly starting at 3 mg and reaching the target dose of 14 mg QD. After three months, the patient demonstrated significant improvements in various parameters such as blood pressure (−10/−8 mmHg), weight (−9.8 kg), waist circumference (−25 cm), serum glucose (−179 mg/dL), HbA1C (−5.7%), triglycerides (−154 mg/dL), LDL (−18 mg/dL), AST (−60 U/L), and ALT (−38 U/L), along with an increase in HDL (+6 mg/dL). After approximately 4 months on the target dose the patient showed further improvements in several parameters including ASCVD risk score (2.1%), blood pressure (−20/12 mmHg), weight (−14.8 kg), waist circumference (−30 cm), serum glucose (−183 mg/dL), HbA1C (−6%), LDL (−25 mg/dL), AST (−63 U/L), and ALT (−40 U/L), and HDL (+10 mg/dL), except for triglyceride levels (−130 mg/dL). Follow-up liver ultrasound showed significant improvement in fatty liver disease. Real-world experiences with newly introduced drugs should be reported, as they may have beneficial effects beyond the ones studied. Oral semaglutide, the first oral GLP-1 analog, has been shown to be non-inferior to other subcutaneous GLP-1 analogs. In this case, improvements were observed in glycemic control, weight loss, lipid levels, and a reduction in cardiovascular risk, as well as an improvement in fatty liver disease. Presentation: Friday, June 16, 2023

SAT085 Oral Glucagon-like Peptide-1 Receptor Agonist As Adjuvant Treatment In HNF1A-MODY

Abstract Disclosure: D.T. Broome: Grant Recipient; Self; NIH U54DK118612-04. Research Investigator; Self; Fractyl Laboratories, Novo Nordisk. Maturity-onset diabetes of the young (MODY) is an inherited form of monogenic diabetes caused by a mutation in a single gene. HNF1A-MODY is the most common treatment-requiring form of MODY with a reported frequency of 1.2%1. Early genetic diagnosis leads to more precise treatment, and sulfonylureas have been recognized as first-line treatment in patients with HNF1A-MODY. Although sulfonylurea treatment is often effective early in the disease course, patients often experience sulfonylurea treatment failure. As a result, there has been recent investigation into additional treatment options that are effective. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) have previously been published for use in patients with HNF1A-MODY2,3, and recognized as a potential effective treatment in patients with HNF1A-MODY. Although GLP-1 RAs have been reported for use as injectable agents, there is currently no evidence reporting their effectiveness as oral medications. In this report, we present a novel case of use of oral semaglutide as adjuvant treatment to sulfonylurea in a patient with HNF1A-MODY. A 48-year-old female with a history of diabetes since age 22, later confirmed as HNF1A-MODY at age 45 (Heterozygous HNF1A mutation, c.608G&amp;gt;A (p.Arg203His), NM_000545.5), was glimepiride for 3 years and without micro- or macrovascular complications. She developed a 15-lb weight gain, and her HbA1c increased to 7% (HbA1c gradually increasing from 5.4% to 7.0% over 3 years) despite her taking glimepiride 4 mg twice daily prescribed by her primary care physician. Thereafter, her primary care physician prescribed oral semaglutide 3 mg once daily for 4 weeks, which was titrated to 7 mg once daily. After initiation of oral semaglutide, her glimepiride was reduced to 2 mg once daily, her HbA1c improved to 5.4%, and she lost 30 lbs over a 6-month timeframe. This is the first report demonstrating the benefits of oral GLP-1 RA treatment in a patient with HNF1A-MODY, and this clinical case provides further support of use GLP-1 RA use as adjuvant treatment to sulfonylurea in patients with HNF1A-MODY.

THU283 Oral Semaglutide, Effectiveness, Safety And Tolerability In Real Life: A Short-term Retrospective Observational Study

Abstract Disclosure: O. Moreno-Perez: None. C. Guillen-Morote: None. T. Argüello: None. C. Soriano: None. E. SantaCruz: None. P. Lopez-Mondejar: None. C. Navarro-Hoyas: None. R. Sanchez-Ortiga: None. M. Sanchez-Pacheco: None. I. Modrego-Pardo: None. A.M. Pico: None. Introduction: Oral semaglutide (oSEMA) is the first and only oral aRGLP1 currently available on the market. Given its recent commercialization, there is little real-life evidence on its effectiveness, safety, and tolerability. Primary objective: to evaluate the effectiveness (HbA1c, Weight, Blood Pressure, Albumin Creatinine Ratio (ACR)) safety and tolerability of oSEMA 3-6 months after the start of treatment in the real world clinical practice. Secondary objective: to describe the main indications of oSEMA in real life. Material and methods: short-term retrospective observational study of all patients with oSEMA prescription in two health departments between November 2021 and November 2022. Statistical approach: descriptive analysis (median [IQR]); Wilcoxon test - paired data for evaluate changes in main outcomes and logistic regression to determine associations between provider speciality and short-term non-adherence. Ethics committee approval Ref.: 2022-0386. Results: 170 patients were included in these preliminary data. The median age was 63 [55.0 -70.0] years, with male predominance (60.5%), initial weight of 95 [83-112]kg and BMI 36.03 [31.04-39.34] Kg/m2. Median T2D evolution was 8 [2.0-12.0] years, 27.3% have an established CVD and 14% DKD. Prior therapy for T2D: 11% GLP1 receptor agonists (RA), 25.6% DPP4 inhibitors, 47.1% SGLT-2 inhibitors and 22.7% under insulin therapy. The oSEMA provider specialties were mainly: endocrinology (ENDO) 39.2%, primary physician (PCare) 35.7% and cardiology (CAR) 20.9%. At the time of this analysis, the maintenance dose was 7 mg in 98.4% of patients. The changes in the main clinical outcomes at 3-6 months of follow-up were: HbA1c 7.8 [6.9-8.6]% vs 6.9 [6.2-7.7]%, p= 0.0001; weight 95.5 [81-112] Kg vs 90 [74.5-105.2]Kg, p= 0.0001; ACR (baseline ACR subpopulation &amp;gt; 30) 57 [39. 5- 110.9] mg/g vs. CAC 37.0 [14.5-58.0], p=0.005; SBP 135 [125-150] mmHg vs. SBP 121.5 [109.50-31.00], p= 0.028. Treatment was discontinued in 23.8% of cases (ENDO 14%, PCare 26, CAR 30%). Having the index prescription ordered by ENDO were associated with lower odds of non-adherence (OR 0.48[0.22-1.05], p = 0.06). The most frequent causes of oSEMA discontinuation were the lack of continuity of care after hospitalization (renewal / titration) (10.5%) and digestive intolerance (8.7%). Conclusions: Oral SEMA at medium doses is effective in the short term with 1% reductions in HbA1c, 5% weight loss and a significant reduction in microalbuminuria. Oral SEMA is usually started in obese PLWT2D naïve to aRGLP1, with inadequate metabolic control and without CV disease. No serious adverse events have been recorded. Mistakes in the transition from hospital discharge to primary care were the cause of almost 50% of short-term non-adherence. Presentation: Thursday, June 15, 2023