A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide

Bækdal, Tine A.; Breitschaft, Astrid; Navarria, Andrea; Hansen, Christian K.

doi:10.1080/17425255.2018.1488965

Cited by 40 publications

(42 citation statements)

References 17 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The question of the impact of omeprazole on PK was also assessed, as elevation of bulk stomach pH might have confounded the purported mechanism of SNAC. Using a 5-mg semaglutide dose in patients taking 40 mg of omeprazole over a 10-day period with a follow-up period out to 21 days, overall PK values for both semaglutide and SNAC were unchanged, leading to a conclusion that dose adjustment would be also unnecessary in patients on concomitant omeprazole [74]. The implications of these findings would support the determination that the pH increase created by SNAC in the stomach must be at the semaglutide tablet surface [52] and does not impact bulk stomach pH; otherwise, a large effect of omeprazole on PK would have been expected.…”

Section: C10 and Snac: Pharmacokinetics And Efficacy In Clinical Tmentioning

confidence: 99%

Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10)

et al. 2019

View full text Add to dashboard Cite

Salcaprozate sodium (SNAC) and sodium caprate (C10) are two of the most advanced intestinal permeation enhancers (PEs) that have been tested in clinical trials for oral delivery of macromolecules. Their effects on intestinal epithelia were studied for over 30 years, yet there is still debate over their mechanisms of action. C10 acts via openings of epithelial tight junctions and/or membrane perturbation, while for decades SNAC was thought to increase passive transcellular permeation across small intestinal epithelia based on increased lipophilicity arising from non-covalent macromolecule complexation. More recently, an additional mechanism for SNAC associated with a pH-elevating, monomer-inducing, and pepsin-inhibiting effect in the stomach for oral delivery of semaglutide was advocated. Comparing the two surfactants, we found equivocal evidence for discrete mechanisms at the level of epithelial interactions in the small intestine, especially at the high doses used in vivo. Evidence that one agent is more efficacious compared to the other is not convincing, with tablets containing these PEs inducing single-digit highly variable increases in oral bioavailability of payloads in human trials, although this may be adequate for potent macromolecules. Regarding safety, SNAC has generally regarded as safe (GRAS) status and is Food and Drug Administration (FDA)-approved as a medical food (Eligen®-Vitamin B12, Emisphere, Roseland, NJ, USA), whereas C10 has a long history of use in man, and has food additive status. Evidence for co-absorption of microorganisms in the presence of either SNAC or C10 has not emerged from clinical trials to date, and long-term effects from repeat dosing beyond six months have yet to be assessed. Since there are no obvious scientific reasons to prefer SNAC over C10 in orally delivering a poorly permeable macromolecule, then formulation, manufacturing, and commercial considerations are the key drivers in decision-making.

show abstract

Section: C10 and Snac: Pharmacokinetics And Efficacy In Clinical Tmentioning

confidence: 99%

Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10)

et al. 2019

View full text Add to dashboard Cite

show abstract

“…11 On the other hand, omeprazole, lisinopril, warfarin, metformin, digoxin, ethinyl estradiol/levonorgestrel, rosuvastatin, and furosemide were evaluated for drug-drug interactions, and none of these agents affected semaglutide concentrations. 9,[12][13][14]…”

Section: Drug Interactionsmentioning

confidence: 99%

Oral Semaglutide: First-in-Class Oral GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus

Cowart

2019

Ann Pharmacother

View full text Add to dashboard Cite

Objective:The purpose of this article is to review the pharmacological characteristics and clinical evidence of oral semaglutide for the treatment of type 2 diabetes mellitus (T2DM). Data Sources: A MEDLINE/PubMed search was conducted between January 1, 2005, and September 30, 2019. Search terms included semaglutide, glucagon-like peptide 1 receptor agonist, GLP-1 receptor agonist, and type 2 diabetes. Study Selection and Data Extraction Quantification: The following study designs were included in the analysis: systematic review and/or meta-analyses, clinical trial, or observational study design. Narrative reviews were excluded. Articles were included only if they were published in the English language or evaluated oral semaglutide with regard to pharmacology, pharmacokinetics, safety, and efficacy in humans. Data Synthesis: Oral semaglutide has been Food and Drug Administration approved for the treatment of T2DM as an adjunct to diet and exercise. Oral semaglutide has been shown to result in an absolute hemoglobin A1C reduction between −0.5% and −1.5% and weight reductions between −1 and −4.7 kg. Oral semaglutide has been shown to be noninferior to placebo for cardiovascular (CV) safety although additional CV outcomes trials are ongoing. Adverse effects appear to be similar to those of other glucagon-like peptide-1 receptor agonists and are gastrointestinal in nature. Relevance to Patient Care and Clinical Practice: Oral semaglutide may be appropriate as second- or third-line add-on therapy for patients with T2DM who are not meeting treatment goals on metformin and are overweight and reluctant to use an injectable drug. Conclusions: Oral semaglutide appears safe and effective as monotherapy and add-on pharmacological therapy for the treatment of T2DM.

show abstract

“…taking oral semaglutide prior to other oral medications and waiting at least 30 minutes before taking any other oral medications) [9]. Pharmacokinetic drug-drug interaction studies suggest no clinically relevant interactions or need for dose adjustment for patients receiving commonly used medications including omeprazole, lisinopril, warfarin, digoxin, metformin, furosemide, rosuvastatin, or the combined oral contraceptive ethinylestradiol/levonorgestrel [73][74][75][76]. When oral semaglutide is administered concomitantly with medications that have narrow therapeutic windows or that require clinical monitoring, increased clinical/laboratory monitoring should be considered [9].…”

Section: Considerations For Patients Taking Other Oral Medicationsmentioning

confidence: 99%

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how?

Brunton

Mosenzon

Wright

2020

Postgraduate Medicine

View full text Add to dashboard Cite

Oral semaglutide is the first US Food and Drug Administration-approved oral glucagon-like peptide-1 receptor agonist (GLP-1RA) for the treatment of type 2 diabetes (T2D). Prior articles within this supplement reviewed the PIONEER trial program, which demonstrated that oral semaglutide reduced glycated hemoglobin and body weight when given to patients with uncontrolled T2D on various background therapies, and had a safety profile consistent with subcutaneous GLP-1RAs. This article provides guidance on integrating oral semaglutide into clinical practice in primary care. Patient populations with T2D who may gain benefit from oral semaglutide include those with inadequate glycemic control taking one or more oral glucose-lowering medication (e.g. after metformin), patients for whom weight loss would be beneficial, patients at risk of hypoglycemia, those who would historically have been considered for treatment with asubcutaneous GLP-1RA, and those receiving basal insulin who require treatment intensification. Like other GLP-1RAs, oral semaglutide is contraindicated in those with personal/family history of medullary thyroid carcinoma, and in those with multiple endocrine neoplasia syndrome type 2, as noted in aboxed warning in the prescribing information. Oral semaglutide has not been studied in those with ahistory of pancreatitis, is not recommended in patients with suspected/ confirmed pancreatitis, and is not indicated in type 1 diabetes. When initiating oral semaglutide, gradual dose escalation is recommended to minimize the risk of gastrointestinal adverse events. As food and excess liquid reduce oral semaglutide absorption, patients should swallow the tablet with up to 4 fl oz/120 mL of water on an empty stomach upon waking, and should wait at least 30 minutes before eating, drinking, or taking other oral medications. Those managing patients should be aware of the potential impact of these dosing conditions on concomitant medications. When counseling patients, it is important to discuss these administration instructions, realistic therapeutic expectations, and strategies for mitigation of gastrointestinal events. Oral semaglutide provides a new option for add-on to initial T2D therapy (or later in the treatment paradigm), with the potential to enable more patients to benefit from the improvements in glycemic control, reductions in body weight, and low risk of hypoglycemia afforded by GLP-1RAs.

show abstract

A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide

Abstract: There was a slight non-statistically significant increase in semaglutide exposure when oral semaglutide was administered with omeprazole, but this is not considered clinically relevant and no dose adjustment is likely to be required.

Cited by 40 publications

References 17 publications

Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10)

Intestinal Permeation Enhancers for Oral Delivery of Macromolecules: A Comparison between Salcaprozate Sodium (SNAC) and Sodium Caprate (C10)

Oral Semaglutide: First-in-Class Oral GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes Mellitus

Integrating oral semaglutide into clinical practice in primary care: for whom, when, and how?

Contact Info

Product

Resources

About