Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis

Abstract

Introduction The relative efficacy and safety of once-daily oral semaglutide vs. injectable glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in subjects with type 2 diabetes (T2D) inadequately controlled on basal insulin were assessed using network meta-analysis (NMA). Methods A systematic literature review (SLR) was performed to identify randomised controlled trials of GLP-1 RAs in this population. Data at 26 ± 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA 1c ), weight and blood pressure; HbA 1c target levels (< 7.0% and ≤ 6.5%); composite endpoint; incidence of nausea, vomiting or diarrhoea. Comparators of interest were all licensed doses of dulaglutide, exenatide, liraglutide, lixisenatide and once-weekly injectable semaglutide. Results The NMA included seven trials. Once-daily oral semaglutide 14 mg was associated with significantly greater HbA 1c reductions vs. most comparators (treatment differences: − 0.42 to − 1.32%); differences vs. once-weekly injectable semaglutide (0.5 mg and 1 mg doses) were not statistically significant. Once-daily oral semaglutide 14 mg was associated with significantly greater weight reductions vs. exenatide 2 mg and lixisenatide 20 μg (− 2.21 and − 2.39 kg respectively); non-statistically significant weight reductions in favour of once-daily oral semaglutide 14 mg were observed vs. all other comparators except once-weekly injectable semaglutide 1 mg. Similar trends were observed for the proportion of subjects achieving HbA 1c < 7.0% and ≤ 6.5% and the composite endpoint. Once-daily oral semaglutide 14 mg was associated with similar odds of experiencing nausea, vomiting or diarrhoea vs. all comparators. Conclusion Once-daily oral semaglutide 14 mg, as an add-on to basal insulin, is an efficacious treatment for reducing HbA 1c and weight and meeting glycaemic targets at 26 ± 4 weeks. Once-daily oral semaglutide 14 mg also offers the option of an oral treatment with similar or better efficacy and similar tolerability vs. most injectable GLP-1 RAs. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01034-w.

Advances in GLP-1 treatment: focus on oral semaglutide

“…A systematic literature review used a network meta-analysis tool to calculate the relative efficacy and safety of once-daily oral semaglutide 14 mg versus dulaglutide 1.5 mg, twice-daily exenatide 10 μg, once-weekly exenatide 2 mg, once-daily liraglutide 1.8 mg, once-daily lixisenatide 20 μg, and once-weekly injectable semaglutide 0.5 and 1.0 mg (all GLP-1 RA class drugs) using seven clinical trials [ 50 ]. The results showed that oral semaglutide significantly reduced HbA1c levels if compared with dulaglutide (− 0.85%, 95% CI − 1.25 to − 0.45), exenatide [− 0.93%, 95% CI − 1.32 to − 0.54 (dose 10 μg) and − 0.89%, 95% CI − 1.27 to − 0.51 (dose 2 mg)], liraglutide (− 0.42%, 95% CI − 0.78 to − 0.05), and lixisenatide (− 1.32%, 95% CI − 1.74 to − 0.91) [ 50 ]. However, reductions in HbA1c were similar for oral and injectable semaglutide [− 0.32%, 95% CI − 0.72 to 0.08 (dose 0.5 mg) and 0.08%, 95% CI − 0.32 to 0.47 (dose 1.0 mg)] [ 50 ].…”

“…The results showed that oral semaglutide significantly reduced HbA1c levels if compared with dulaglutide (− 0.85%, 95% CI − 1.25 to − 0.45), exenatide [− 0.93%, 95% CI − 1.32 to − 0.54 (dose 10 μg) and − 0.89%, 95% CI − 1.27 to − 0.51 (dose 2 mg)], liraglutide (− 0.42%, 95% CI − 0.78 to − 0.05), and lixisenatide (− 1.32%, 95% CI − 1.74 to − 0.91) [ 50 ]. However, reductions in HbA1c were similar for oral and injectable semaglutide [− 0.32%, 95% CI − 0.72 to 0.08 (dose 0.5 mg) and 0.08%, 95% CI − 0.32 to 0.47 (dose 1.0 mg)] [ 50 ]. Oral semaglutide also significantly reduced weight compared to exenatide 2 mg (− 2.21 kg, 95% CI − 3.45 to − 0.92) and lixisenatide (− 2.39 kg, 95% CI − 3.66 to − 1.14) [ 50 ].…”

“…However, reductions in HbA1c were similar for oral and injectable semaglutide [− 0.32%, 95% CI − 0.72 to 0.08 (dose 0.5 mg) and 0.08%, 95% CI − 0.32 to 0.47 (dose 1.0 mg)] [ 50 ]. Oral semaglutide also significantly reduced weight compared to exenatide 2 mg (− 2.21 kg, 95% CI − 3.45 to − 0.92) and lixisenatide (− 2.39 kg, 95% CI − 3.66 to − 1.14) [ 50 ]. The other comparators were similar to oral semaglutide in bodyweight reduction [ 50 ].…”

“…Oral semaglutide also significantly reduced weight compared to exenatide 2 mg (− 2.21 kg, 95% CI − 3.45 to − 0.92) and lixisenatide (− 2.39 kg, 95% CI − 3.66 to − 1.14) [ 50 ]. The other comparators were similar to oral semaglutide in bodyweight reduction [ 50 ]. According to safety, oral semaglutide provided similar odds of experiencing nausea and diarrhea compared with all other GLP-1 RA comparators [ 50 ].…”

“…The other comparators were similar to oral semaglutide in bodyweight reduction [ 50 ]. According to safety, oral semaglutide provided similar odds of experiencing nausea and diarrhea compared with all other GLP-1 RA comparators [ 50 ]. On the other hand, the chance of vomiting was lower for oral semaglutide compared with dulaglutide [Odds ratios (OR) 0.03, 95% CI 0.01–0.73] and lixisenatide (OR 0.06, 95% CI 0.01–0.82) [ 50 ].…”