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Semaglutide injection bests canagliflozin, liraglutide in head-to-head type 2 diabetes trials
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Favorable results from separate SUSTAIN trials pitting the GLP-1 receptor agonist semaglutide against the SGLT2 inhibitor canagliflozin and against the popular GLP-1 receptor agonist liraglutide were presented and simultaneously published in journals.
In both studies, adults with type 2 diabetes randomly assigned a once-weekly regimen of 1 mg semaglutide injection (Ozempic, Novo Nordisk) experienced greater HbA1c and body weight reductions vs. those assigned the comparator regimen.
Comparing drug classes
In SUSTAIN 8, Ildiko Lingvay, MD, associate professor of internal medicine at University of Texas Southwestern Medical Center, and colleagues randomly assigned 788 adults (mean age, 56.6 years; 46% women) with type 2 diabetes uncontrolled with metformin equally to weekly semaglutide injection or daily 300 mg oral canagliflozin (Invokana, Janssen).
“Because of the effectiveness of these two drug classes, they are now recommended as second-line treatment options after metformin and lifestyle modifications for patients with a wide variety of characteristics in our practice,” Lingvay said during a presentation. “Despite this wide endorsement of the use of these two classes, there are very few head-to-head comparative trials evaluating one class vs. the other.”
At 52 weeks, the semaglutide group experienced a mean 1.5% decrease from baseline in HbA1c vs. 1% for the canagliflozin group (P < .0001). Among the semaglutide group, 66% had an HbA1c below 7% and 53% below 6.5% vs. 45% and 24%, respectively, for the canagliflozin group (P < .0001 for both).
Mean weight loss from baseline at 52 weeks was 5.3 kg with semaglutide vs. 4.2 kg with canagliflozin (P = .0029), and 22% of those in the semaglutide group lost at least 10% of their body weight vs. 9% of the canagliflozin group (P < .0001). In addition, 7% of those taking semaglutide vs. 1% of those taking canagliflozin lost 15% of their body weight (P = .0004) based on post hoc analysis.
In contrast, the canagliflozin group experienced greater mean decreases in blood pressure than the semaglutide group: 5.5 mm Hg vs. 3.5 mm Hg in systolic and 3 mm Hg vs. 1 mm Hg in diastolic BP (P = .045 and P < .0001, respectively).
Adverse event rates were similar between the groups, although the researchers noted gastrointestinal events with semaglutide and more infections and infestations in the canagliflozin group.
In a commentary accompanying the article, André J. Scheen, MD, PhD, of the division of diabetes, nutrition and metabolic disorders in the department of medicine and the division of clinical pharmacology, center for interdisciplinary research on medicines at the University of Liège in Belgium, wrote that these findings do not necessarily mean that GLP-1 receptor agonists should always be preferred to SGLT2 inhibitors. He noted that the higher cost and injection delivery of GLP-1 receptor agonists can make that class a less appealing choice for some patients. He also noted that SUSTAIN 8 does not address cardiovascular and renal effects of the two drug classes.
Comparing GLP-1 receptor agonists
In SUSTAIN 10, Matthew S. Capehorn, BMedSci, MBChB, clinical manager of the Rotherham Institute for Obesity (RIO) and partner at Clifton Medical Centre in the U.K., and colleagues randomly assigned 577 adults (mean age, 59.5 years; 43.3% women; mean HbA1c, 8.2%; mean body weight, 96.9 kg) with type 2 diabetes uncontrolled on other oral medications equally to semaglutide or 1.2 mg liraglutide (Victoza, Novo Nordisk) for 30 weeks.
“I personally see this as a very valuable study in the context of real-world practice,” Capehorn told Endocrine Today. “We have previously had other studies within the SUSTAIN program that have compared semaglutide against other competitor drugs, but we cannot get away from the fact that one of the most commonly prescribed GLP-1 analogues across Europe is liraglutide — and the most commonly prescribed dose, whether for reasons of reimbursement or perceived cost-effectiveness, is 1.2 mg once daily — and so we needed evidence to help clinicians to consider using this newer agent rather than stick with those that are tried and tested.”
At 30 weeks, the semaglutide group experienced a mean 1.7% decrease in HbA1c vs. 1% for the liraglutide group. Among the semaglutide group, 80% had an HbA1c below 7% and 58% below 6.5% vs. 46% and 25%, respectively, of the liraglutide group. Of those taking semaglutide, 83% had an HbA1c decrease of at least 1% vs. 48% of those taking liraglutide (P < .0001 for all).
Mean weight loss from baseline at 30 weeks was 5.8 kg with semaglutide vs. 1.9 kg with liraglutide, and 73% of those taking semaglutide lost at least 3% of their body weight vs. 34% of those taking liraglutide. In addition, 56% of the semaglutide group lost at least 5% of their body weight and 19% lost at least 10% vs. 18% and 4%, respectively, of those taking liraglutide (P < .0001 for all).
At 30 weeks, 76% of the semaglutide group had not gained weight and reached an HbA1c below 7% vs. 37% of the liraglutide group. Additionally, among those who had at least a 1% decrease in HbA1c, 62% of the semaglutide group vs. 21% of the liraglutide group had at least a 3% weight loss; 50% had at least a 5% weight loss with semaglutide vs. 12% with liraglutide; and 17% had at least a 10% weight loss with semaglutide vs. 4% with liraglutide (P < .0001 for all).
Adverse events were similar between the groups, according to the researchers.
“It seems clear that, in practice, clinicians may have the dilemma as to whether to continue to prescribe 1.2 mg once-daily liraglutide or consider 1 mg once-weekly semaglutide,” Capehorn said. “SUSTAIN 10 offers the evidence for clinicians facing this prescribing dilemma. Semaglutide is superior to liraglutide for HbA1c and body weight reduction, and with a similar overall safety profile, accepting slightly more initial gastrointestinal side effects. Given the cost of semaglutide, it seems a clear choice that prescribers should consider once-weekly semaglutide over once-daily liraglutide.” – by Phil Neuffer
- References:
- Capehorn MS. OP 53.
- Capehorn MS, et al. Diabetes Metab. 2019;doi:10.1016/j.diabet.2019.101117.
- Lingvay I, et al. Abstract 52. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 16-20, 2019; Barcelona, Spain.
- Lingvay I, et al. Lancet Diabetes Endocrinol. 2019;doi:10.1016/S2213-8587(19)30311-0.
- Scheen AJ. Lancet Diabetes Endocrinol. 2019;doi:10.1016/S2213-8587(19)30310-9.
Disclosures: The studies were funded by Novo Nordisk. Capehorn reports he has received advisory board support, research support and/or speaker fees from Abbott, Boehringer, GlaxoSmithKline, Ingelheim/Lilly, Janssen, Leo, Merck Sharp & Dohme, Novartis and Novo Nordisk. Lingvay reports she has received consultant fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Intarcia, Johnson & Johnson, Mannkind, Novo Nordisk, Sanofi, TARGET PharmaSolutions and Valeritas, and research grants from Novo Nordisk, Gan & Lee, GI Dynamics, Merck, Mylan, Novartis and Pfizer. Scheen reports no relevant financial disclosures. Please see the studies for all other authors’ relevant financial disclosures.