Two long-acting GLP-1 agonists have differing efficacy, tolerability

Reuters Health Information: Two long-acting GLP-1 agonists have differing efficacy, tolerability

Two long-acting GLP-1 agonists have differing efficacy, tolerability

Last Updated: 2018-02-14

By Reuters Staff

NEW YORK (Reuters Health) - Results of an open-label study provide more evidence of variability in efficacy and tolerability of agents in the long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist class of diabetes medicines.

The SUSTAIN 7 study assessed two once-weekly GLP-1R agonists, semaglutide and dulaglutide, at both low and high approved doses, in about 1,200 patients with type 2 diabetes not well controlled with metformin.

Both drugs showed good glycemic efficacy over the course of 40 weeks, but semaglutide proved superior to dulaglutide at lowering HbA1c and helping patients lose weight.

From baseline, HbA1c was reduced by 1.5 and 1.8 percentage points with semaglutide 0.5 mg and 1.0 mg, respectively, versus 1.1 and 1.4 percentage points with dulaglutide 0.75 and 1.5 mg, respectively (P<0.0001 for both comparisons). In addition, more patients taking semaglutide achieved HbA1c of less than 7.0% without severe or confirmed symptomatic hypoglycemia and no weight gain compared with dulaglutide.

From baseline, mean body weight was reduced by 4.6 kg and 6.5 kg with semaglutide 0.5 mg and 1.0 mg, respectively, compared with 2.3 kg and 3.0 kg with dulaglutide 1.5 mg (P<0.0001 for both).

"Weight loss was observed across all treatment groups; however, the magnitude of weight loss achieved with semaglutide was double the amount achieved with dulaglutide at both dose levels. Accordingly, twice as many semaglutide-treated patients achieved clinically relevant weight loss of more than 5% as did dulaglutide-treated patients," Dr. Richard Pratley from the Translational Research Institute for Metabolism and Diabetes, in Orlando, Florida, and colleagues note in The Lancet Diabetes & Endocrinology, online January 31.

The adverse event profiles of both GLP-1R agonists were largely similar and consistent with those from prior studies. Gastrointestinal problems were the most common adverse events with both agents and the most common reason for treatment discontinuation.

"Although the proportion of premature treatment discontinuation due to occurrence of adverse events was less than 10% in all treatment groups, it was higher for each dose level of semaglutide compared with the respective dose level of dulaglutide," the researchers report.

There was no evidence for increased risk of progression of diabetic retinopathy in SUSTAIN 7, something that was observed in the SUSTAIN 6 study.

In a linked comment, Dr. Abd Tahrani from the University of Birmingham, UK, and colleagues say it's important to note that the SUSTAIN 7 findings "apply to patients who were only on metformin and who were at relatively low cardiovascular risk since patients with renal impairment, established cardiovascular disease, and advanced diabetic retinopathy were excluded. Additionally, much more information as to the relative usefulness within the class of these drugs from real world settings is required to establish their true place in the management of type 2 diabetes."

They also note that differences in efficacy between GLP-1R agonists have been seen in several head-to-head trials "without clear explanations."

"When choosing the next glucose lowering drug for patients with type 2 diabetes, healthcare practitioners need to consider multiple factors in addition to glycemic efficacy to personalize treatment approaches on the basis of individualized treatment targets," they advise. "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."

The SUSTAIN 7 study was funded by Novo Nordisk, which makes semaglutide. Several of the study authors reported relationships with the company.


Lancet Diabetes Endocrinol 2018.

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