Effects Of Oral Semaglutide Research Articles

Effect of oral semaglutide on energy intake, appetite, control of eating and gastric emptying in adults living with obesity: A randomized controlled trial.

To investigate the effects of once-daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. A clinical pharmacology, double-blind study was conducted in 61 adults with obesity randomized to once-daily oral semaglutide (dose-escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant-reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was -39.2% points (95% confidence interval -59.0%, -19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. In participants with obesity, once-daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption.

1708-P: Effect of Oral Semaglutide in Glycemic Control and Weight Reduction for People with Type 2 Diabetes Mellitus Having a BMI ≥25 kg/m2—A Six-Month Real-World Study

1708-P: Effect of Oral Semaglutide in Glycemic Control and Weight Reduction for People with Type 2 Diabetes Mellitus Having a BMI ≥25 kg/m2—A Six-Month Real-World Study

Oral semaglutide effectiveness and safety in real world practice; The REVOLUTION study

AimsThis study seeks to provide insights into the practical application and effects of oral semaglutide in Saudi T2DM patients under routine medical supervision. MethodsThe primary outcome measure was the laboratory HbA1c. Secondary measures included fasting blood glucose (FBG), weight, and hypoglycemia. All variables were checked after six months and 12 months of initiation. ResultsThe analysis of this study included 245 uncontrolled (HbA1c > 7 %) T2DM patients. The mean baseline HbA1c was 10.1 % (1.2). HbA1c was reduced by an average of 3.1 % (0.8) and 3.2 % (0.8) at 6 and 12 months, respectively. The frequency of hypoglycemia events in the last three months before semaglutide was initiated was 4.4 (1.1). The frequency of hypoglycemia events in the last three months was 2.2 (0.8) and 0.7 (0.4) at 6-month and 12-month follow-up visits, respectively. The percent reduction in body mass index (BMI) was an average of 13.0 % (1.4) and 19.7 % (3.4) at six months and 12 months, respectively. Lipid profile and blood pressure were improved at six months and 12 months. ConclusionsOral semaglutide provided substantial glycemic and weight-loss benefits in adult individuals with T2DM.

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.

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

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

Oral semaglutide improves body composition and preserves lean mass in patients with type 2 diabetes: a 26-week prospective real-life study.

Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy. Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared. A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed. Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D.

Audit on the effect of oral Semaglutide on HbA1c and Weight reduction in type 2 diabetes

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

Effects of oral semaglutide on the lipid profile of patients with type 2 diabetes mellitus and obesity: Are they mediated by body weight loss?

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

Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial.

To describe the design of the SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) and the baseline clinical data of its participants. In SOUL, the effects of oral semaglutide, the first oral glucagon-like peptide-1 receptor agonist, on the risk of cardiovascular (CV) events in individuals with type 2 diabetes and established atherosclerotic CV disease (ASCVD) and/or chronic kidney disease (CKD) will be assessed. SOUL is a randomized, double-blind, parallel-group, placebo-controlled CV outcomes trial comparing oral semaglutide (14 mg once daily) with placebo, both in addition to standard of care, in individuals aged ≥50 years with type 2 diabetes and evidence of ASCVD (coronary artery disease [CAD], cerebrovascular disease, symptomatic peripheral arterial disease [PAD]) and/or CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 ). The primary outcome is time from randomization to first occurrence of a major adverse CV event (MACE; a composite of CV death, nonfatal myocardial infarction or nonfatal stroke). This event-driven trial will continue until 1225 first adjudication-confirmed MACEs have occurred. Enrolment has been completed. Overall, 9650 participants were enrolled between June 17, 2019 and March 24, 2021 (men 71.1%, White ethnicity 68.9%, mean age 66.1 years, diabetes duration 15.4 years, body mass index 31.1 kg/m2 , glycated haemoglobin 63.5 mmol/mol [8.0%]). The most frequently used antihyperglycaemic medications at baseline were metformin (75.7%), insulin and insulin analogues (50.5%), sulphonylureas (29.1%), sodium-glucose cotransporter-2 inhibitors (26.7%) and dipeptidyl peptidase-4 inhibitors (23.0%). At randomization, 70.7% of participants had CAD, 42.3% had CKD, 21.1% had cerebrovascular disease and 15.7% had symptomatic PAD (categories not mutually exclusive). Prevalent heart failure was reported in 23.0% of participants. SOUL will provide evidence regarding the CV effects of oral semaglutide in individuals with type 2 diabetes and established ASCVD and/or CKD.

The Effect of Oral Semaglutide in Combination with other Hypoglycemic Agents in Patients with Diabesity

The twin epidemic of diabesity is a major concern in current practice. Treatment strategies that benefit weight and glycemia are the need of the hour. Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 inhibitors are known to have a beneficial effect on weight reduction. Further, patients are often noncompliant with injectable medications despite the medications being effective. GLP-1 receptor agonist is one of the high glycemic efficacy therapies that can potentially reduce the risk of cardio-renal diseases. Until recently, GLP-1 receptor agonists were available in an injectable formulation. Semaglutide is the first in this class of drugs available as an oral formulation. Direct and indirect evidence has confirmed the safety and efficacy of semaglutide, including oral formulation. There are no trial data on oral semaglutide in Indian subjects with type 2 diabetes and obesity. We present a series of case reports where semaglutide was added to achieve adequate glycemic control with the added benefit of weight loss. Oral semaglutide was associated with a 1.5% reduction in glycosylated haemoglobin and 3–14 kg weight reduction after 3 months. Large clinical trials must confirm the findings from isolated cases, though the Indian population also responded as reported cases.

Effects of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide on glucose metabolism in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, parallel-group comparison study (the SWITCH-SEMA 2 study)

IntroductionIncretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on...

Effect of Oral Semaglutide on Cardiovascular Parameters and Their Mechanisms in Patients with Type 2 Diabetes: Rationale and Design of the Semaglutide Anti-Atherosclerotic Mechanisms of Action Study (SAMAS).

IntroductionType 2 diabetes (T2D) management has reached a point where not only optimal glycaemic control is necessary, but also additional interventions with proven cardiovascular risk reduction benefit. Subcutaneous semaglutide has been shown to provide cardiovascular protection, but its use may be limited by its injection formulation. To overcome this limitation, an oral semaglutide tablet has been developed, which could potentially be of the same value as its injection counterpart, but in a much wider group of patients with T2D, thereby allowing for broader cardiovascular risk reduction in this vulnerable patient population.MethodsA total of 100 consecutive patients with T2D and a disease duration of up to 10 years, without manifest cardiovascular disease, who are treated with metformin (± sulphonylurea) and optimal cardioprotective therapy, will be recruited in a single-blinded, randomized trial named “Semaglutide Anti-atherosclerotic Mechanisms of Action Study (SAMAS).” After 1:1 randomization, patients will receive either oral semaglutide 14 mg daily or placebo for 1 year. The primary outcome comprises changes in atherosclerosis-related structural and functional characteristics of the arterial wall, namely: reduction of the carotid intima-media thickness, improvement of endothelial function and decrease in arterial stiffness. Secondary outcomes are changes in atherogenic small dense low-density lipoproteins, glucose control (HbA1c) and inflammatory markers (hsCRP). Possible correlations between primary endpoints and changes in lipids, HbA1c and high-sensitivity C-reactive protein will be sought.DiscussionThis is the first study to investigate the direct and indirect anti-atherosclerotic mechanisms of oral semaglutide. The results are expected to confirm the position of oral semaglutide in the multifactorial management of T2D with an emphasis on cardiovascular disease prevention.Trial RegistrationClinicalTrials.gov Identifier: NCT05147896.

Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial

ABSTRACT Background Oral semaglutide comprises the glucagon-like peptide-1 analog, semaglutide, and sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Levothyroxine has similar dosing conditions to oral semaglutide. This trial investigated if oral semaglutide co-administered with levothyroxine affects thyroxine (T4) exposure and if multiple placebo tablets co-administered with oral semaglutide affect semaglutide exposure. Research design and methods In this one-sequence crossover trial, 45 healthy subjects received levothyroxine (600 μg single-dose) alone, or with concomitant SNAC 300 mg or concomitant oral semaglutide 14 mg at steady-state. Subjects also received oral semaglutide 14 mg at steady-state alone or with five placebo tablets once-daily for 5 weeks. Results A 33% increase in total T4 exposure was observed with levothyroxine/oral semaglutide vs levothyroxine alone, but baseline-corrected maximum concentration (C max) was unaffected. SNAC alone did not affect total T4 exposure, whereas C max was slightly decreased. A 34% decrease in semaglutide exposure was observed when oral semaglutide was co-administered with placebo tablets, and C max also decreased. Conclusions Levothyroxine pharmacokinetics were influenced by co-administration with oral semaglutide. Monitoring of thyroid parameters should be considered when treating patients with both oral semaglutide and levothyroxine. Oral semaglutide exposure was influenced by co-administration with multiple tablets, which is addressed in the dosing guidance.

56 - Effect of Oral Semaglutide With or Without Background SGLT2i in Patients With T2D: Subgroup Analysis of PIONEER 4

56 - Effect of Oral Semaglutide With or Without Background SGLT2i in Patients With T2D: Subgroup Analysis of PIONEER 4

927-P: Effect of Oral Semaglutide with or without Background SGLT2i in Patients with T2D: Subgroup Analysis of PIONEER 4

Glucagon-like peptide-1 receptor agonists (GLP-1RA) and SGLT2 inhibitors (SGLTi) are widely used to treat type 2 diabetes (T2D) but trial data on their combined use are limited. We report the first data on oral semaglutide in combination with SGLT2i. This was a post-hoc subgroup analysis of the 52-week, double-blind, double-dummy PIONEER 4 trial (NCT02863419), in which patients with T2D uncontrolled on metformin with or without SGLT2i were randomized 2:2:1 to once-daily oral semaglutide 14 mg, subcutaneous (s.c.) liraglutide 1.8 mg or placebo. Glycated hemoglobin (HbA1c) and body weight (BW) data presented are for the trial product estimand (on-trial product without rescue medication). In total, 183 (26%) of 711 patients were receiving SGLT2i treatment at baseline which continued throughout the trial. Subgroups of patients receiving SGLT2i had a lower percentage of females, slightly longer mean T2D duration and higher BW. Changes in HbA1c and BW were similar in patients receiving oral semaglutide or s.c. liraglutide with or without SGLT2i. Occurrence of most gastrointestinal adverse events was similar in patients on GLP-1RA with and without SGLT2i. In conclusion, improvements in HbA1c and BW after one year as well as safety profile were similar in patients on GLP-1RA with or without background SGLT2i. Disclosure R.E. Pratley: Other Relationship; Self; AstraZeneca, Eli Lilly and Company, GlaxoSmithKline plc., Glytec, Janssen Scientific Affairs, LLC., Lexicon Pharmaceuticals, Inc., Ligand Pharmaceuticals Incorporated, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. R. Bauer: Employee; Self; Novo Nordisk A/S. S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck &amp; Co., Inc., vTv Therapeutics. K. Khunti: Advisory Panel; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Board Member; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Consultant; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier. Speaker’s Bureau; Self; Amgen, AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Menarini Group, Merck Sharp &amp; Dohme Corp., Napp Pharmaceuticals, Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi-Aventis, Servier. E.B. Kreiner: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P.N. Laursen: Employee; Self; Novo Nordisk A/S. J.J. Meier: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Funding Novo Nordisk A/S

932-P: Efficacy and Safety of Oral Semaglutide by Baseline Age in the PIONEER Clinical Trial Program

In an exploratory analysis of 7 global phase 3a trials (PIONEER 1-5, 7, and 8) we evaluated the effect of age at baseline on efficacy (&amp;lt;45, ≥45-&amp;lt;65, or ≥65 years) and safety (&amp;lt;65 or ≥65 years) for oral semaglutide (3, 7, 14 mg once daily) vs. comparators in patients with type 2 diabetes. Efficacy endpoints were change from baseline in HbA1c and body weight. Across all trials, there were 582, 3392, and 1683 patients aged &amp;lt;45, ≥45-&amp;lt;65, and ≥65 years, respectively. Baseline HbA1c was similar across age groups, whereas baseline body weight tended to be higher in younger patients. Overall, reductions in HbA1c were comparable across age groups for all trials and were generally larger with oral semaglutide than comparators, irrespective of age (Table). Body weight reductions were greater for oral semaglutide vs. comparators but without association between age and reductions in body weight. In general, proportions of patients with adverse advents (AEs) and AEs leading to treatment discontinuation were greater in the ≥65 vs. the &amp;lt;65 age group for oral semaglutide and comparators (Table). To conclude, the greater effects of oral semaglutide vs. comparators on HbA1c and body weight were seen for patients regardless of age group in the global PIONEER trials. For the &amp;lt;65 and ≥65 age groups, the safety profile of oral semaglutide was in line with other GLP-1RAs. Overall, there was a generally higher discontinuation rate in older patients. Disclosure V.R. Aroda: Consultant; Self; Duke, Novo Nordisk Inc., Sanofi. Employee; Spouse/Partner; Merck &amp; Co., Inc. Research Support; Self; Applied Therapeutics, Fractyl Laboratories, Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; IMNE, Medscape. R. Bauer: Employee; Self; Novo Nordisk A/S. C.L. Hertz: Employee; Self; Novo Nordisk A/S. E. Montanya: Advisory Panel; Self; Sanofi. Consultant; Self; Novartis Pharmaceuticals Corporation. Employee; Spouse/Partner; Almirall. Speaker’s Bureau; Self; AstraZeneca, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S. R. Sørrig: Employee; Self; Novo Nordisk A/S. M.L. Warren: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk Inc., Sanofi. Research Support; Self; Eli Lilly and Company, Gan &amp; Lee Pharmaceuticals, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. B. Cariou: Advisory Panel; Self; Bristol-Myers Squibb, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; GENFIT. Research Support; Self; Amgen, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Abbott, AstraZeneca. Funding Novo Nordisk A/S

PDB9 THE COMPARATIVE EFFICACY OF ORAL SEMAGLUTIDE FOR THE TREATMENT OF TYPE 2 DIABETES MELLITUS (T2DM): A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (NMA)

To evaluate the efficacy of the oral GLP-1 receptor agonist semaglutide compared to liraglutide (an injectable GLP-1 receptor agonist), empagliflozin (an SGLT-2 inhibitor), sitagliptin (a DPP-4 inhibitor), and no treatment beyond ongoing background antihyperglycemic treatment in adults with T2DM. We performed a systematic literature search in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials through October 2019 to identify trials of oral semaglutide and our active comparators measuring intermediate outcomes (e.g., HbA1c) or key measures of benefit (e.g., cardiovascular outcomes). We also included trials measuring key benefits of injectable semaglutide to inform the effects of semaglutide as a molecule. Data informing the comparison of semaglutide and our comparators on key benefits were synthesized in fixed effects Bayesian NMAs. We included 12 randomized controlled trials (RCTs)—eight from the Phase III PIONEER program and four cardiovascular outcomes trials (CVOTs) of our active comparators and injectable semaglutide. Results from the PIONEER trials showed oral semaglutide reduced HbA1c and body weight at follow-up (26-78 weeks) more than placebo, sitagliptin, and liraglutide and reduced HbA1c but had similar effects on body weight compared to empagliflozin. Results from our NMA on findings from the CVOTs showed semaglutide (oral and injectable) reduced the risk of major cardiovascular events more than placebo (hazard ratio [HR]: 0.76; 95% credible interval [95% CrI]: 0.63-0.93) and sitagliptin (HR: 0.77; 95% CrI: 0.61-0.96); no significant differences were found between semagltuide and liraglutide or empagliflozin. Additionally, NMA results showed empagliflozin reduced the risk of hospitalization for heart failure more than semaglutide (HR: 0.63; 95% CrI: 0.42-0.95). Oral semaglutide produced significant reductions in HbA1c and body weight compared to placebo, sitagliptin, and liraglutide and significant reductions in HbA1c compared to empagliflozin. The effect of oral semaglutide on key benefits could only be assessed by indirect comparisons that are potentially susceptible to effect modification.

SAT-140 A Drug-Drug Interaction Trial of Oral Semaglutide with Levothyroxine and Multiple Coadministered Tablets

Introduction: Oral semaglutide contains the GLP-1 analog semaglutide co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). Aims: This trial investigated (A) the effect of oral semaglutide and SNAC alone on the pharmacokinetics (PK) of levothyroxine (thyroxine), a frequently used oral medication with similar dosing instructions to oral semaglutide, and (B) the effect of multiple co-administered tablets on oral semaglutide PK. Methods: This was a 2-part, open-label, one-sequence crossover trial in 45 healthy subjects. Part A comprised three periods during which subjects received single-dose thyroxine 600 μg alone, with SNAC 300 mg, and with oral semaglutide 14 mg at steady-state. Primary endpoint was area under the total thyroxine (T4) serum concentration-time curve (0-48 h) after thyroxine, baseline-corrected for endogenous total T4 (bcAUC0-48h,T4). No effect of oral semaglutide or SNAC alone was declared if the 90% CI for the treatment ratio (thyroxine ± oral semaglutide or SNAC) was entirely within the pre-defined interval (0.80-1.25). In part B, oral semaglutide 14 mg at steady-state was co-administered with 5 placebo tablets (used as model tablets) once-daily for 5 weeks. Primary endpoint was area under the semaglutide plasma concentration-time curve during a 0-24 h dosing interval at steady state (AUC0-24h); no effect was confirmed if the 90% CI for the treatment ratio (oral semaglutide ± placebo) was entirely within the pre-defined interval (0.7000-1.4286). Safety and tolerability were also assessed. Results: In part A, co-administration of steady-state oral semaglutide with thyroxine resulted in a 33% increase in bcAUC0-48h,T4; the 90% CI for the treatment ratio was not within the no effect interval. Oral semaglutide had no effect on baseline-corrected maximum total T4 concentration (bcCmax,T4). Co-administration of SNAC alone did not increase exposure of total T4. In part B, co-administration of multiple tablets with steady-state oral semaglutide resulted in decreased semaglutide AUC0-24 (34%) and Cmax (32%); part of the treatment ratio 90% CIs were not within the no effect interval for both endpoints. The safety profile was as expected for GLP-1 receptor agonists with gastrointestinal adverse events the most frequent. Conclusion: PK of thyroxine were influenced by co-administration of steady-state oral semaglutide. However, no change in clinical practice is required as close monitoring of co-administered thyroxine is already part of medical guidance. No obvious effect was seen with SNAC alone so increased thyroxine exposure may be due to the known gastric emptying delaying effect of the GLP-1 component. Absorption of oral semaglutide is affected by co-administration with multiple tablets (5), which is addressed in clinical dosing guidance.

Oral Semaglutide Does Not Affect the Bioavailability of the Combined Oral Contraceptive Ethinylestradiol/Levonorgestrel

Semaglutide is a glucagon-like peptide (GLP-1) analog co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), to allow oral administration. The effect of oral semaglutide on the pharmacokinetics (PK) of the combined oral contraceptive (OC) ethinylestradiol (EE; 0.03 mg)/levonorgestrel (LN; 0.15 mg) was assessed in an open-label, one sequence crossover trial. Healthy post-menopausal females (n=25) received 8 days of OC alone and 8 days of OC with oral semaglutide (dose escalated to steady state at week 6: 1 week at 3 mg dose, 1 week at 7 mg dose, 4 weeks at 14 mg dose). Primary endpoints were the areas under the plasma concentration−time curve for EE and LN during a dosing interval (0−24 h) at steady state (AUC0−24h,SS). Secondary endpoints included other PK parameters, safety and tolerability. Total exposure of EE and LN were similar for OC alone vs. OC with oral semaglutide, and oral semaglutide did not affect the maximum plasma exposure (Cmax,SS) of EE or LN. AUC0−24h,SS and Cmax,SS ratios for EE and LN were within the predefined no effect interval (0.8−1.25) (Figure). Adverse events with oral semaglutide were consistent with previous trials and expected GLP-1 receptor agonist class effects. These data indicate that oral semaglutide did not affect the bioavailability of the combined OC. Disclosure A. Bôrsting Jordy: Employee; Self; Novo Nordisk A/S. A. Breitschaft: None. E. Christiansen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S. C. Granhall: Employee; Self; Novo Nordisk A/S. C.W. Hansen: Employee; Self; Novo Nordisk A/S. A. Houshmand-Oregaard: Employee; Self; Novo Nordisk A/S. T.A. Baekdal: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S.