February 05, 2018
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SUSTAIN 7: Semaglutide superior to dulaglutide for lowering HbA1c

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Richard Pratley
Richard E. Pratley

Adults with type 2 diabetes assigned semaglutide 0.5 mg or 1 mg had greater reductions in HbA1c and body weight compared with those assigned to dulaglutide 0.75 mg or 1.5 mg, according to an analysis of data from the SUSTAIN 7 clinical trial published in The Lancet Diabetes & Endocrinology.

Richard E. Pratley, MD, Samuel E. Crockett Chair in Diabetes Research, director of research and education at Florida Hospital Diabetes Institute and senior investigator and diabetes program head at the Translational Research Institute for Metabolism and Diabetes in Orlando, Florida, and colleagues evaluated data on adults with type 2 diabetes to determine the effects of semaglutide (Ozempic, Novo Nordisk) at two doses and dulaglutide (Trulicity, Lilly) at two doses on HbA1c and body weight over 40 weeks.

Participants were randomly assigned to subcutaneous semaglutide 0.5 mg (n = 301; mean age, 56 years; 56% men; 77% white; mean HbA1c, 8.3%; mean diabetes duration, 7.7 years), dulaglutide 0.75 mg (n = 299; mean age, 55 years; 54% men; 78% white; mean HbA1c, 7%; mean diabetes duration, 7 years), semaglutide 1 mg (n = 300; mean age, 55 years; 54% men; 81% white; mean HbA1c, 8.2%; mean diabetes duration, 7.3 years) or dulaglutide 1.5 mg (n = 299; mean age, 56 years; 57% men; 74% white; mean HbA1c, 8.2%; mean diabetes duration, 7.6 years) between Jan. 6 and June 22, 2016.

At week 40, the reduction in HbA1c was greater in the semaglutide 0.5-mg group compared with the dulaglutide 0.75-mg group (1.5 percentage points vs. 1.1 percentage points) as well as the semaglutide 1-mg group compared with the dulaglutide 1.5-mg group (1.8 percentage points vs. 1.4 percentage points; P < .0001 for both for noninferiority and superiority). The reduction in mean body weight was also greater in the semaglutide 0.5-mg group compared with the dulaglutide 0.75-mg group (4.6 kg vs. 2.3 kg; P < .0001) as well as the semaglutide 1-mg group compared with the dulaglutide 1.5-mg group (6.5 kg vs. 3 kg; P < .0001).

Participants in both semaglutide groups compared with the dulaglutide groups were more likely to achieve HbA1c less than 7% or HbA1c 6.5% or less at week 40 (P < .0001 for the low-dose comparison; P = .0021 for the high-dose comparison) and achieve weight loss of at least 5% or at least 10% (P < .0001 for all).

Adverse events occurred in 68% of the semaglutide 0.5-mg group, 62% of the dulaglutide 0.75-mg group, 69% of the semaglutide 1-mg group and 74% of the dulaglutide 1.5-mg group. Gastrointestinal disorders were the most frequent adverse events reported.

“This study illustrates that there are important differences within the class of GLP-1 agonists with respect to both glycemic efficacy and weight loss,” Pratley told Endocrine Today. “We now have better treatment options for helping our patients achieve their goals. In a shared decision-making interaction with patients, we can offer a treatment that will more than likely get them an HbA1c goal of less than 7% and at the same time promote significant weight loss. And importantly, these benefits are available with a simple to use, well-tolerated once-weekly injection.”

“While a pre-approved study (SUSTAIN 6) indicated that semaglutide may have a significant cardiovascular benefit, this needs to be confirmed in a robust cardiovascular outcome study,” he said. “The potential benefits of semaglutide in patients with obesity and prediabetes also need to be elucidated.”

In an accompanying commentary, Abd A. Tahrani, MD, MRCP, PhD, a National Institute for Health Research clinician scientist at the University of Birmingham in the United Kingdom, and colleagues wrote that multiple factors in addition to glycemic efficacy should be considered by health care practitioners when choosing glucose-lowering drugs for individual patients with type 2 diabetes.

“Such factors might include the effect on weight, hypoglycemia, cardiovascular risk, diabetes-related complications, tolerability, ease of use, durability of effects, interactions with other drugs, a patient’s age, and renal or hepatic impairment,” they wrote. “Although two head-to-head trials of other weekly GLP-1 agonists have shown glycemia and weight advantages with semaglutide, treatment decisions should allow for differences in trial designs and the generalizability of the findings in a real-life setting.” – by Amber Cox

For more information:

Richard E. Pratley, MD, can be reached at richard.pratley@flhosp.org.

Disclosures: Pratley reports he receives research grants (to his institution) from Novo Nordisk; speaker and consultancy fees (to his institution) from AstraZeneca and Takeda; consultancy fees (to his institution) from Boehringer Ingelheim, Eisai, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceutical Co., Janssen, Ligand Pharmaceuticals, Merck, Novo Nordisk and Pfizer; and research grants from Eli Lilly, Gilead Sciences, Lexicon Pharmaceutical, Ligand Pharmaceuticals, Merck, Novo Nordisk, Sanofi-Aventis U.S. and Takeda. Tahrani reports he receives grants from the National Institute for Health Research U.K.; personal fees and nonfinancial support from AstraZeneca and Boehringer Ingelheim; non-financial support from Eli Lilly; and grants from Novo Nordisk and Sanofi Aventis outside the submitted work. Please see the study and comment for all other authors’ relevant financial disclosures.