SUSTAIN 8: Semaglutide bests canagliflozin in head-to-head type 2 diabetes trial
Adults with type 2 diabetes randomly assigned to a GLP-1 receptor agonist experienced a greater reduction in HbA1c and lost more weight than those assigned to an SGLT2 inhibitor in a head-to-head trial of the two drug classes, according to findings presented at the European Association for the Study of Diabetes annual meeting and simultaneously published in The Lancet Diabetes & Endocrinology.
“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,” Ildiko Lingvay, MD, a professor in the department of internal medicine/endocrinology, department of clinical sciences at the University of Texas Southwestern Medical Center in Dallas, 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.”
Lingvay and colleagues analyzed data from the SUSTAIN 8 trial, which included 788 adults (mean age, 56.6 years; 46% women) with type 2 diabetes who were using metformin but still had an HbA1c of 7% to 10.5%. The researchers randomly assigned participants equally to a once per week regimen of 1 mg semaglutide injection (Ozempic, Novo Nordisk) to represent the GLP-1 receptor agonist class or a once per day regimen of 300 mg oral canagliflozin (Invokana, Janssen) to represent the SGLT2 inhibitor class. The 52-week study was made up of 8 weeks of titration and 44 weeks of regular treatment. The researchers were primarily interested in the differences in the effects on HbA1c and body weight between the two groups.
HbA1c and weight loss
Those taking semaglutide experienced a mean 1.5 percentage point decrease in HbA1c after 52 weeks compared with a mean 1 percentage point decrease for those taking canagliflozin (P < .0001). Among those taking semaglutide, 66% had an HbA1c below 7% after treatment while 45% of those taking canagliflozin had an HbA1c below 7% after treatment (P < .0001). In addition, 53% of those taking semaglutide had an HbA1c of 6.5% or less after treatment while 24% of those taking canagliflozin had an HbA1c of 6.5% or less after treatment (P < .0001).
Those taking semaglutide lost an average of 5.3 kg in body weight after 52 weeks compared with a loss of 4.2 kg for those taking canagliflozin (P = .0029). Among those taking semaglutide, 22% lost at least 10% of their baseline body weight vs. 9% of the canagliflozin group (P < .0001). The researchers also noted that 7% of those taking semaglutide and 1% of those taking canagliflozin lost 15% of their baseline body weight (P = .0004) based on post hoc analysis.
In addition, the researchers found that those taking semaglutide experienced a mean 2.3 mmol/mol decrease in fasting plasma glucose vs. a mean 2 mmol/mol decrease for those taking canagliflozin (P = .0094). The semaglutide group also experienced a mean 2.8 mmol/mol decrease in 7-point self-monitoring of blood glucose profile compared with a 2 mmol/mol decrease for those taking canagliflozin (P < .0001) and a mean 0.7 mmol/mol decrease in postprandial SMBG increments vs. a mean 0.4 mmol/mol decrease for those taking canagliflozin (P = .036).
When examining the effects of each medication on blood pressure, the researchers found greater mean decreases for the canagliflozin group: Those taking semaglutide experienced mean decreases of 3.5 mm Hg in systolic and 1 mm Hg in diastolic BP compared with mean decreases of 5.5 mm Hg and 3 mm Hg, respectively, for those taking canagliflozin (P = .045 and P < .0001, respectively).
Those taking semaglutide experienced 1,189 adverse events, with 67% of those considered mild by the researchers. Those taking canagliflozin experienced 1,138 adverse events, with 64% of those considered mild by the researchers. Although these rates were similar, the researchers noted that those taking semaglutide were more susceptible to gastrointestinal events whereas those taking canagliflozin were more susceptible to infections and infestations.
“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes as second-line therapy in patients with type 2 diabetes,” Lingvay said.
In a commentary accompanying the article in The Lancet Diabetes & Endocrinology, André J. Scheen, MD, PhD, of the division of diabetes, nutrition and metabolic disorders in the department of medicine at Centre Hospitalier Universitaire de Liège and of the division of clinical pharmacology, center for interdisciplinary research on medicines at University of Liège in Belgium, wrote that these findings do not necessarily mean that semaglutide and other 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. – by Phil Neuffer
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 study was funded by 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. Please see the study for all other authors’ relevant financial disclosures. Scheen reports no relevant financial disclosures.