Oral Semaglutide Research Articles

Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes

Background and aimsTo assess the safety and efficacy of semaglutide compared with placebo and other anti-hyperglycaemic agents in type 2 diabetes (T2DM). MethodsWe searched PubMed, Scopus, Web of Science, and Cochrane library for relevant randomized controlled trials (RCTs). A network meta-analysis was conducted to compare different doses, durations, and interventions in T2DM. We presented results as mean difference (MD) or relative risk (RR) and 95% confidence interval (CI). ResultsTwenty-six included RCTs studied different doses of subcutaneous (SC) and oral semaglutide, tirzepatide, liraglutide, sitagliptin, canagliflozin, and empagliflozin compared with placebo. Tirzepatide showed the highest efficacy, however, it was comparable to semaglutide. SC semaglutide 1 mg once-weekly showed higher reduction in HbA1c (MD = −1.72, 95% CI [-2.32; −1.12]), and fasting blood glucose (MD = −1.93, 95% CI [-2.81; −1.04]) versus placebo at 30 weeks and other timepoints. Adverse events (ADs) were comparable to placebo with oral and SC semaglutide, oral sitagliptin, SC liraglutide, and oral empagliflozin at most timepoints. However, SC semaglutide 0.8 mg and tirzepatide 10 mg groups had the highest gastrointestinal adverse events. ConclusionTirzepatide, oral and SC semaglutide has a favourable efficacy in treating T2DM. The adverse events were comparable to placebo; however, gastrointestinal adverse events were highly recorded in tirzepatide, oral and SC semaglutide groups.

Effects of Semaglutide on Stroke Subtypes in Type 2 Diabetes: Post Hoc Analysis of the Randomized SUSTAIN 6 and PIONEER 6

Background:GLP-1 RA (glucagon-like peptide-1 receptor agonists), including semaglutide, may reduce stroke risk in people with type 2 diabetes. This post hoc analysis examined the subcutaneous and oral semaglutide effects, versus placebo, on stroke and its subtypes in people with type 2 diabetes at high cardiovascular risk.Methods:SUSTAIN 6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects With Type 2 Diabetes) and PIONEER 6 (Peptide Innovation for Early Diabetes Treatment) were randomized cardiovascular outcome trials of subcutaneous and oral semaglutide in people with type 2 diabetes at high cardiovascular risk, respectively. Time to first stroke and stroke subtypes were analyzed using a Cox proportional hazards model stratified by trial with pooled treatment as a factor. The impact of prior stroke, prior myocardial infarction or stroke, age, sex, systolic blood pressure, estimated glomerular filtration rate, and prior atrial fibrillation on treatment effects was assessed using interaction P values. Risk of major adverse cardiovascular event was analyzed according to prior stroke.Results:A total of 106/6480 participants had a stroke (1.0 event/100 patient-years of observation [PYO]). Semaglutide reduced incidence of any stroke versus placebo (0.8 versus 1.1 events/100 PYO; hazard ratio, 0.68 [95% CI, 0.46–1.00]; P=0.048), driven by significant reductions in risk of small-vessel occlusion (0.3 versus 0.7 events/100 PYO; hazard ratio, 0.51 [95% CI, 0.29–0.89]; P=0.017). Hazard ratios for risk of any stroke with semaglutide versus placebo were 0.60 (95% CI, 0.37–0.99; 0.5 versus 0.9 events/100 PYO) and 0.89 (95% CI, 0.47–1.69; 2.7 versus 3.0 events/100 PYO) in those without and with prior stroke, respectively. Except for prior atrial fibrillation (Pinteraction=0.025), no significant interactions were observed between treatment effects on risk of any stroke and subgroups investigated, or between treatment effects on risk of major adverse cardiovascular event and prior stroke (Pinteraction >0.05 for all).Conclusions:Semaglutide reduced incidence of any first stroke during the trials versus placebo in people with type 2 diabetes at high cardiovascular risk, primarily driven by small-vessel occlusion prevention. Semaglutide treatment, versus placebo, lowered the risk of stroke irrespective of prior stroke at baseline.Registration:URL: https://www.clinicaltrials.gov; Unique identifier: NCT01720446 and NCT02692716.

The Cost-Effectiveness of Oral Semaglutide in Spain: A Long-Term Health Economic Analysis Based on the PIONEER Clinical Trials.

Novel glucagon-like peptide-1 (GLP-1) receptor agonist oral semaglutide has demonstrated greater improvements in glycated hemoglobin (HbA1c) and body weight versus oral medications empagliflozin and sitagliptin, and injectable GLP-1 analog liraglutide, in the PIONEER clinical trial program. Based on these data, the present analysis aimed to evaluate the long-term cost-effectiveness of oral semaglutide versus empagliflozin, sitagliptin and liraglutide in Spain. Outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 3.0% annually. Cohort characteristics and treatment effects were sourced from PIONEER 2 and 4 for the comparisons of oral semaglutide 14mg versus empagliflozin 25mg and liraglutide 1.8mg, respectively, and PIONEER 3 for oral semaglutide 7 and 14mg versus sitagliptin 100mg. Costs were accounted from a healthcare payer perspective in 2020 euros (EUR). Patients were assumed to receive initial therapies until HbA1c exceeded 7.5% and then treatment-intensified to basal insulin. Oral semaglutide 14mg was associated with improvements in quality-adjusted life expectancy of 0.13, 0.19 and 0.06 quality-adjusted life years (QALYs) versus empagliflozin 25mg, sitagliptin 100mg and liraglutide 1.8mg, respectively, with direct costs EUR168 higher versus empagliflozin and EUR236 and 1415 lower versus sitagliptin and liraglutide, respectively. Oral semaglutide 14mg was associated with an incremental cost-effectiveness ratio (ICER) of EUR1339 per QALY gained versus empagliflozin and was considered dominant (clinically superior and cost saving) versus sitagliptin and liraglutide. Additional analyses demonstrated that oral semaglutide 7mg was associated with improvements of 0.11QALYs and increased costs of EUR226 versus sitagliptin and was therefore associated with an ICER of EUR2011 per QALY gained. Oral semaglutide 14mg was dominant versus sitagliptin and liraglutide, and cost-effective versus empagliflozin, for the treatment of type 2 diabetes in Spain.

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

AimsTo evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes.Materials and MethodsChange from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme. Treatment differences were analysed using a mixed model for repeated measurements for continuous variables and a logistic regression model for the binary endpoint. Pooled safety data were analysed descriptively.ResultsChanges from baseline in HbA1c and body weight, and the odds of achieving HbA1c <7.0%, were greater with oral semaglutide 14 mg/flex (n = 1934) and higher or similar with oral semaglutide 7 mg (n = 823) versus comparators (n = 2077) across most subgroups. Changes in HbA1c with oral semaglutide 14 mg/flex were greater for patients with higher baseline HbA1c (HbA1c >9.0%: –1.7% to –2.6%; HbA1c <8.0%: –0.7% to –1.2%). In some trials, Asian patients experienced greater HbA1c reductions with oral semaglutide 14 mg/flex (–1.5% to –1.8%) than other racial groups (–0.6% to –1.6%). The overall incidence of adverse events (AEs) with oral semaglutide was similar to that with comparators and was consistent across subgroups. More gastrointestinal AEs were observed with oral semaglutide, versus comparators, across subgroups.ConclusionsOral semaglutide demonstrated consistently greater HbA1c and body weight reductions across a range of patient characteristics, with greater HbA1c reductions seen at higher baseline HbA1c levels.

Oral Semaglutide: Dosage in Special Situations.

Glucagon-like peptide 1 receptor agonists (GLP1RAs) have recently gained momentum after the introduction of semaglutide, the first oral molecule in their class. In a recent article in this journal by Evans et al., a succinct overview of the utility of semaglutide is highlighted in the context of virtual diabetes care. To take this discussion further, this commentary describes the value and positioning of oral semaglutide in common clinical situations. Its insights assist in pragmatic placement of this drug in clinical practice. Special emphasis is laid on the use of oral semaglutide in persons already on injectable GLP-1RA formulations, those experiencing sudden changes in life style pattern due to religious, social, or professional commitments, individuals seeking help for urgent glycemic control, and those who face sudden change in their concomitant medications or comorbidities.

Insights into the early use of oral semaglutide in routine clinical practice

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

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...

Abstract #1161775: Semaglutide-induced leukocytoclastic vasculitis

Semaglutide is a GLP-1 receptor agonist approved for treatment of type 2 diabetes mellitus. Common side effects include mild and transient gastrointestinal disturbance. It increases the risk of cholelithiasis. No major safety concerns have arisen to date, although definitive conclusions regarding risk of pancreatic and medullary thyroid cancer cannot be drawn at this point. We describe a patient who developed leukocytoclastic vasculitis with oral semaglutide.

Orální semaglutid - Rybelsus®, první agonista GLP-1 receptoru pro perorální použití v klinické praxi

Glucagon like peptide-1 receptor agonists (GLP-1 RA) are potent antidiabetic drugs associated with significant weight loss and minimal risk of hypoglycemia. Semaglutide is a GLP-1 RA with a proven cardiovascular benefit. It is currently also available in oral form, which is especially suitable for the treatment of the initial phase of type 2 diabetes. However, it is also effective at later initiation of therapy, in different diabetic populations. The PIONEER 6 trial demonstrated cardiovascular safety of oral semaglutide, its administration was accompanied by a significant reduction in cardiovascular and overall mortality.

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.

Efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes: A subgroup analysis by baseline variables in the PIONEER 9 and PIONEER 10 trials.

Aims/IntroductionTo assess the impact of baseline characteristics on the efficacy and safety of oral semaglutide in Japanese patients with type 2 diabetes.Materials and MethodsIn the Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) 9 and 10 trials, Japanese patients were randomized to once‐daily oral semaglutide (3, 7, or 14 mg) or a comparator (placebo or once‐daily subcutaneous liraglutide 0.9 mg in PIONEER 9; once‐weekly subcutaneous dulaglutide 0.75 mg in PIONEER 10) for 52 weeks, with 5 weeks of follow up. An exploratory analysis grouped patients in each trial according to baseline glycated hemoglobin (HbA1c; ≤8.0, >8.0–≤9.0, or >9.0%), body mass index (<25, ≥25–<30, or ≥30 kg/m2) and, for PIONEER 10 only, by background medication (sulfonylurea, glinide, thiazolidinedione, α‐glucosidase inhibitor, sodium‐glucose cotransporter 2 inhibitor). Efficacy (changes from baseline to week 26 in HbA1c and bodyweight) and safety were assessed.ResultsSeven hundred and one patients were included (PIONEER 9: N = 243; PIONEER 10: N = 458). In both trials, HbA1c reductions increased as baseline HbA1c increased; there were no other apparent patterns between the variables investigated and HbA1c or bodyweight changes. There was one statistically significant subgroup interaction between baseline HbA1c and estimated treatment differences in bodyweight change for oral semaglutide 14 mg versus placebo in PIONEER 9 (P = 0.0286). Baseline HbA1c, baseline body mass index and background medication did not appear to affect the proportions of patients reporting adverse events.ConclusionsOral semaglutide is effective across a range of baseline subgroups of Japanese patients with type 2 diabetes, with no unexpected safety findings.

Abstract 25: Glycemic variability of oral semaglutide versus empagliflozin: A post hoc analysis of PIONEER 2

Glycemic variability is associated with markers of microvascular and macrovascular complications and impacts quality of life in patients with type 2 diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to both improve HbA1c concentration and reduce glycemic variability in patients with type 2 diabetes. GLP-1RAs increase insulin secretion and suppress glucagon in a glucose-dependent manner, which may partly explain their ability to reduce glycemic variability. However, it is not clear if HbA1c influences the effect of GLP-1RAs on glycemic variability. Oral semaglutide, the first GLP-1RA available as an oral formulation, is effective at reducing HbA1c vs a range of comparators, but its effect on glycemic variability needs to be understood. Therefore, we have assessed the change in glycemic variability and its possible relationship with HbA1c in a 52-week randomized, open-label trial (PIONEER 2) comparing oral semaglutide with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin in patients with type 2 diabetes uncontrolled on metformin. The seven-point self-measured blood glucose profile (7-point SMBG) was assessed at baseline and at weeks 26 and 52 in the PIONEER 2 trial. The standard deviation (SD) of the measurements in the 7-point SMBG profile was used as a measure of glycemic variability. An additional post-hoc mediation analysis was performed to explore the indirect effect of HbA1c concentration on the direct relationship between treatment and glycemic variability (the SD of the 7-point SMBG) at weeks 26 and 52. The results showed that the SD of the 7-point SMBG at baseline for the once-daily oral semaglutide 14 mg (N=411) and empagliflozin 25 mg (N=410) treatment arms was 2.06 and 2.05 mmol/l, respectively. The change from baseline in the SD of the 7-point SMBG in the oral semaglutide and empagliflozin arms was -0.67 and -0.44 mmol/l, respectively, at week 26, and -0.69 and -0.49 mmol/l, respectively, at week 52. The treatment differences (95% CI) for the SD of the 7-point SMBG for oral semaglutide vs empagliflozin at weeks 26 and 52 were -0.23 (-0.33, -0.12; p<0.0001) and -0.20 (-0.31, -0.09; p=0.0003) mmol/l, respectively. The mediation analysis showed that the indirect effect of HbA1c accounted for -0.06 (-0.10, -0.02; p=0.0029) and -0.03 (-0.06, 0.00; p=0.08) mmol/l of the treatment difference for the SD of the 7-point SMBG at weeks 26 and 52, respectively. In conclusion the oral semaglutide significantly reduces glycemic variability, as assessed by the SD of the 7-point SMBG, compared with empagliflozin, and most of this effect was not explained by an indirect effect of HbA1c.Clinical Trial Registration Number: NCT02863328

Semaglutide: A Strategic Weapon for Primary Care

Type 2 diabetes has been a long-standing concern worldwide and in Singapore. Having one of the highest diabetes prevalence rates in Southeast Asia, Singapore has explored various ways of enhancing the management of chronic illnesses, one of which is to treat diabetic patients in primary care settings rather than speciality facilities. Primary care physicians are tasked to manage their diabetic patients’ glycated haemoglobin levels, along with a myriad of related complications including hypoglycaemia, cardiovascular risk, and body weight issues. With the ever-increasing complexity of population health demands, oral semaglutide can be a strategic weapon utilised by primary care doctors to treat type 2 diabetic patients. In terms of glycaemic control and body weight reduction, oral semaglutide has outperformed several other oral anti-diabetic medicines. Moreover, oral semaglutide has a proven cardiovascular safety profile with potential benefits. The development of oral semaglutide, rather than the injectable type, has made it simpler for patients to benefit from semaglutide treatment. Oral semaglutide is a feasible and effective strategy in type 2 diabetes management, for both initiation and intensification needs, and is well positioned to be a game changer in primary care.

Abstract 138: Efficacy of oral semaglutide according to race: An exploratory subgroup analysis of the PIONEER trial program

The global PIONEER program investigated the efficacy and safety of oral semaglutide, a glucagon-like peptide-1 receptor agonist. Patients with type 2 diabetes were randomized to once-daily oral semaglutide (3, 7 or 14 mg, or flexibly dosed [flex]), placebo, or active comparator (empagliflozin 25 mg, sitagliptin 100 mg or liraglutide 1.8 mg). This exploratory subgroup analysis evaluated the effect of race on glycated hemoglobin (HbA1c) and body weight (BW) reductions at the end of treatment (week 26, 52 or 78). Data were analyzed from PIONEER 1-5, 7 and 8 by race (White, Asian, Black/African American). Baseline characteristics were generally similar across subgroups except for BW, which was lower in Asian patients. Generally, greater HbA1c reductions were observed with oral semaglutide 14 mg/flex vs. comparators across subgroups [Table 1]. In PIONEER 1, 4 and 8, there was a significant interaction between treatment and race, with greater HbA reductions and estimated treatment differences in Asian patients than in other subgroups [Table 1]. Overall, BW reductions were greater for oral semaglutide vs. comparators, regardless of subgroup and without significant interactions between treatment and race. Our findings in this exploratory subgroup analysis suggest that, in some PIONEER trials, Asian patients achieve greater HbA reductions than other race groups when treated with oral semaglutide.

A Review of Oral Semaglutide Available Evidence: A New Era of Management of Diabetes with Peptide in a Pill Form.

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have gained an important place in the management of diabetes management because of their exceptional glucose-lowering, weight lowering and cardiovascular (CV) benefits. Despite recommendations by various clinical practice guidelines and benefits, their usage in clinical practice was limited because of being injectable in nature. Oral semaglutide is a novel GLP-1RA with 94% homology to human GLP-1 which is co-formulated with absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), that overcomes the challenges of peptide absorption in the acidic conditions of the stomach. Oral semaglutide has been evaluated in an extensive phase 3 clinical trial programme named Peptide Innovation for Early Diabetes Treatment (PIONEER) which demonstrated its robust glucose and weight lowering effects against other comparators. The evolution of the GLP-1RA class to include an oral pill will facilitate the use of this class of agents much earlier in the diabetes treatment cascade owing to wider acceptance from patients and clinicians alike. The current review discusses the various aspects of oral semaglutide and its place in clinical practice.

Abstract 15: Glycemic and body weight responses to oral semaglutide in the PIONEER trial program

Case: The PIONEER phase 3 program investigated glycemic response and other efficacy endpoints in patients (pts) with type 2 diabetes randomized to the glucagon-like peptide-1 analog oral semaglutide (sema; 3, 7 or 14 mg once daily), placebo (pbo) or an active comparator (empagliflozin [empa] 25 mg, sitagliptin [sita] 100 mg or liraglutide [lira] 1.8 mg once daily). This post-hoc analysis of the PIONEER 1-5 and 8 trials evaluated the response of any reduction in HbA (%) and/or body weight (%), and a clinically relevant composite endpoint of HbA1c reduction ≥1% and body weight loss ≥5%, with oral sema 14 mg vs. comparators at the end of treatment (26-78 weeks). Across trials, any reduction in HbA1c was observed in higher proportions of pts with oral sema (89- 95%) than with pbo (51-64%) or active comparators (82-88%). A simultaneous reduction in both HbA1c and body weight was seen in 72-86% of pts treated with oral sema. The composite of HbA1c reduction ≥1% and body weight loss ≥5% was achieved by 27-41% of pts with oral sema, 1-8% of pts with pbo, 11% with sita 100 mg, 18% with lira 1.8 mg, and 20% with empa 25 mg. Within each trial, the odds of achieving HbA1c reduction of ≥1% and body weight loss of ≥5% with oral sema 14 mg were significantly greater vs. all comparators.

Abstract 34: Time spent in glycemic control after initiating treatment with oral semaglutide versus empagliflozin: An exploratory analysis of the PIONEER 2 trial

A standard objective in the management of T2D is the achievement and maintenance of HbA1C targets, but the duration of time that patients spend within glycemic control targets has not been previously reported for oral semaglutide (sema). In this exploratory analysis, the duration of time that patients were in glycemic control (HbA1C <7.0% and <6.5%) during the 52-week PIONEER 2 trial (NCT02863328) was assessed. Patients with uncontrolled T2D (N=822; HbA1C 7.0─10.5%) were randomized to oral sema 14 mg once daily or empagliflozin (empa) 25 mg once daily. Both drugs underwent dose escalation, with oral sema starting at 3 mg, increasing to 7 mg after 4 weeks, and 14 mg after 8 weeks. Empa was initiated at 10 mg and escalated to 25 mg after 8 weeks. For this analysis, outcomes were evaluated using the on-treatment without rescue medication observation period, in all randomized patients. Baseline characteristics were similar between treatment arms. Mean baseline HbA1C for both arms was 8.1%. A greater proportion of patients receiving oral sema vs. empa achieved HbA1C <7.0% at some point during the study (78% vs. 60%), and for the following lengths of time that HbA1C remained <7%: ≥14 weeks (65% vs. 48%); ≥26 weeks (56% vs. 38%); and ≥38 weeks (46% vs. 28%). During treatment, the overall mean duration of time spent at HbA1C <7.0% and <6.5% was 27 weeks and 16 weeks, respectively, for oral sema, and 19 weeks and 7 weeks for empa. Based on the trial product estimand, the odds of patients achieving HbA1C <7.0% at both week 26 and 52 were significantly greater with oral sema vs. empa (estimated odds ratio 4.12 [95% CI 2.94, 5.76]; p<0.0001). In conclusion, despite an 8-week dose escalation schedule and a mean baseline HbA1C of 8.1%, nearly half of patients receiving oral sema achieved glycemic control (HbA1C <7.0%) for more than 70% of the 52-week treatment duration. These data suggest that patients spend more time in glycemic control during treatment with oral sema vs. empa.

Useful Oral Administration of Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA) as Semaglutide (Rybelsus) for Type 2 Diabetes Mellitus (T2DM)

As recommended pharmacological agents for type 2 diabetes mellitus (T2DM), Glucagon-Like Peptide 1 receptor agonist (GLP-1Ra) is highly evaluated for its various beneficial effects. Among them, semaglutide (Rybelsus) has been in focus for useful oral formation with useful oral hypoglycemic agent (OHA). Administration per os is possible due to the developed technique of absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate. Clinical efficacy was shown by a series of Peptide Innovation for Early Diabetes Treatment (PIONEER) with enough weight reduction and decreased HbA1c. From the results of several PIONEER programs, oral semaglutide 14 mg/day had reduced HbA1c values by approximately 1.0-1.4%.

Usefulness of Empagliflozin Versus Oral Semaglutide for Prevention of Cardiovascular Mortality in Patients With Type 2 Diabetes Mellitus

Empagliflozin and oral semaglutide reduce the incidence of cardiovascular mortality (CVM) in patients with type 2 diabetes mellitus. However, these therapies impose a significant financial burden on healthcare systems. Therefore, we compared the value for money of empagliflozin versus oral semaglutide to prevent CVM. We calculated the cost needed to treat to prevent 1 case of CVM using either drug by multiplying the annualized number needed to treat to prevent 1 event by the annual cost of the therapy. Efficacy estimates were extracted from published randomized controlled trials data. We performed a scenario analysis to mitigate the primary differences between the populations of randomized controlled trials. Drug costs were calculated as 75% of the United States National Average Drug Acquisition Cost listing.The annualized number needed to treat for empagliflozin in EMPA-REG-OUTCOME was 141 (95% confidence interval [CI] 104 to 230) and 141 (95% CI 96 to 879) for oral semaglutide in PIONEER 6. The annual treatment costs are $4,797 for empagliflozin versus $7,133 for oral semaglutide. Therefore, the corresponding costs needed to treat are $676,385 ($498,894-$1,101,039) and $1,005,855 (95% CI $684,837-$6,270,544) respectively. In conclusion, our findings suggest that empagliflozin provides better value for money than oral semaglutide to prevent CVM in patients with type 2 diabetes mellitus at the current United States prices of the interventions.

The long-term cost-effectiveness of oral semaglutide versus empagliflozin and dulaglutide in Portugal

BackgroundOral semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog that has been associated with improvements in glycated hemoglobin (HbA1c) and body weight versus sodium-glucose cotransporter-2 inhibitor empagliflozin and injectable GLP-1 receptor agonist dulaglutide in the PIONEER 2 clinical trial and in a recent network meta-analysis (NMA), respectively. The aim of the present study was to evaluate the long-term cost-effectiveness of oral semaglutide 14 mg versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes from a healthcare payer perspective in Portugal.MethodsIn two separate analyses, outcomes were projected over patients’ lifetimes using the IQVIA CORE Diabetes Model (v9.0), discounted at 4% per annum. Clinical data were sourced from the PIONEER 2 trial and the NMA for the comparisons versus empagliflozin and dulaglutide, respectively. Patients were assumed to receive initial therapies until HbA1c exceeded 7.5%, then treatment-intensified to solely basal insulin therapy. Costs were accounted from a National Healthcare Service perspective in Portugal and expressed in 2021 euros (EUR). Utilities were taken from published sources.ResultsOral semaglutide 14 mg was associated with improvements in life expectancy of 0.10 and 0.03 years, and quality-adjusted life expectancy of 0.11 and 0.03 quality-adjusted life years (QALYs), versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively. Improved clinical outcomes were due to a reduced cumulative incidence and increased time to onset of diabetes-related complications with oral semaglutide. Total costs were projected to be EUR 2548 and EUR 814 higher with oral semaglutide versus empagliflozin and dulaglutide, with higher acquisition costs partially offset by cost savings from avoidance of diabetes-related complications. Oral semaglutide 14 mg was therefore associated with incremental cost-effectiveness ratios of EUR 23,571 and EUR 23,927 per QALY gained versus empagliflozin 25 mg and dulaglutide 1.5 mg, respectively.ConclusionsBased on a willingness-to-pay threshold of EUR 30,000 per QALY gained, oral semaglutide 14 mg was considered cost-effective versus empagliflozin 25 mg and dulaglutide 1.5 mg for the treatment of type 2 diabetes in Portugal.