In the Journals

Safety, efficacy profiles vary among once-weekly GLP-1 receptor agonists

A recently published systematic evidence review and meta-analysis failed to clarify the most favorable safety and efficacy profile for treating type 2 diabetes with once-weekly glucagon-like peptide-1 receptor agonists.

“Available data suggest differences in cardiometabolic outcomes and safety among once-weekly GLP-1 [receptor agonists],” the researchers wrote.

Francesco Zaccardi, MD, of the Diabetes Research Centre at Leicester General Hospital in the United Kingdom, and colleagues evaluated data from electronic databases and congress abstracts through Sept. 26, 2015, on 34 randomized controlled trials with 24 or more weeks of follow-up. The GLP-1 receptor agonists included Tanzeum (albiglutide, GlaxoSmithKline), Trulicity (dulaglutide, Lilly), Bydureon (extended-release exenatide, AstraZeneca), semaglutide and taspoglutide.

Although all GLP-1 receptor agonists were associated with reductions in HbA1c values, dulaglutide 1.5 mg led to a greater mean reduction compared with dulaglutide 0.75 mg, albiglutide and taspoglutide 10 mg and 20 mg. No difference in mean HbA1c level was found when compared with exenatide.

A comparison of all GLP-1 receptor agonists revealed that exenatide resulted in a greater fasting plasma glucose reduction compared with albiglutide, dulaglutide 0.75 mg and taspoglutide 10 mg; no significant differences were found in comparison with taspoglutide 20 mg and dulaglutide 1.5 mg.

Taspoglutide 20 mg resulted in greater body-weight reductions compared with taspoglutide 10 mg, albiglutide and dulaglutide 0.75 mg; no significant differences were found when compared with dulaglutide 1.5 mg and exenatide. No significant differences were found among the treatments for diastolic blood pressure, total cholesterol or C-reactive protein, whereas small differences were found for LDL, HDL, triglycerides and systolic BP.

Compared with placebo, increased risk for documented or symptomatic hypoglycemia were found for albiglutide (OR = 1.82; 95% CI, 1.05-3.15), taspoglutide 10 mg (OR = 1.94; 95% CI, 1.03-3.62), once-weekly exenatide (OR = 2.08; 95% CI, 1.14-3.82), dulaglutide 0.75 mg (OR = 2.51; 95% CI, 1.39-4.54) and dulaglutide 1.5 mg (OR = 2.69; 95% CI, 1.51-4.82); no significant differences were found for taspoglutide 20 mg compared with placebo.

Compared with the other treatments, taspoglutide 20 mg revealed the greatest risk for nausea. “The results suggested similar effects of these drugs on several cardiometabolic outcomes, such as BP, blood lipids and C-reactive protein, and a modest increase in heart rate with once-weekly exenatide vs. albiglutide (mean difference, 3 beats/min),” the researchers wrote. “Conversely, we found appreciable differences for HbA1c, [FPG] and body weight, with greater reductions for dulaglutide 1.5 mg, once-weekly exenatide and taspoglutide 20 mg compared with albiglutide and other once-weekly GLP-1 [receptor agonists] at lower doses. We also found differences in the risk for nausea, which was highest for taspoglutide 20 mg and 10 mg and dulaglutide 1.5 mg. Conversely, the risk for documented or symptomatic hypoglycemic did not differ among once-weekly GLP-1 [receptor agonists].”

In an accompanying editorial, Victor M. Montori, MD, MSc, and Rene Rodriguez-Gutierrez, MD, both of the department of medicine at the Mayo Clinic in Rochester, Minnesota, wrote that the top priority may be to address the individual’s situation to find the best antihyperglycemic drug class.

“The next priority should be selecting the best drug within that class, but this can be obfuscated by poor-quality evidence, even when summarized, and by marketing claims that hype trivial differences or mechanistic features of unclear value,” they wrote. “In contrast, drug benefit companies and formulary designers, in their efforts to optimize business outcomes, narrow the options by promoting one product while making competing products unaffordable or unavailable. Clinicians and patients must select the most tolerable and least expensive agent that patients can implement.” – by Amber Cox

Disclosure: Zaccardi and Rodriguez-Gutierrez report no relevant financial disclosures. Montori reports being an employee of the Knowledge and Evaluation Research Unit at Mayo Clinic. Please see the full study for a list of all other authors’ relevant financial disclosures.

A recently published systematic evidence review and meta-analysis failed to clarify the most favorable safety and efficacy profile for treating type 2 diabetes with once-weekly glucagon-like peptide-1 receptor agonists.

“Available data suggest differences in cardiometabolic outcomes and safety among once-weekly GLP-1 [receptor agonists],” the researchers wrote.

Francesco Zaccardi, MD, of the Diabetes Research Centre at Leicester General Hospital in the United Kingdom, and colleagues evaluated data from electronic databases and congress abstracts through Sept. 26, 2015, on 34 randomized controlled trials with 24 or more weeks of follow-up. The GLP-1 receptor agonists included Tanzeum (albiglutide, GlaxoSmithKline), Trulicity (dulaglutide, Lilly), Bydureon (extended-release exenatide, AstraZeneca), semaglutide and taspoglutide.

Although all GLP-1 receptor agonists were associated with reductions in HbA1c values, dulaglutide 1.5 mg led to a greater mean reduction compared with dulaglutide 0.75 mg, albiglutide and taspoglutide 10 mg and 20 mg. No difference in mean HbA1c level was found when compared with exenatide.

A comparison of all GLP-1 receptor agonists revealed that exenatide resulted in a greater fasting plasma glucose reduction compared with albiglutide, dulaglutide 0.75 mg and taspoglutide 10 mg; no significant differences were found in comparison with taspoglutide 20 mg and dulaglutide 1.5 mg.

Taspoglutide 20 mg resulted in greater body-weight reductions compared with taspoglutide 10 mg, albiglutide and dulaglutide 0.75 mg; no significant differences were found when compared with dulaglutide 1.5 mg and exenatide. No significant differences were found among the treatments for diastolic blood pressure, total cholesterol or C-reactive protein, whereas small differences were found for LDL, HDL, triglycerides and systolic BP.

Compared with placebo, increased risk for documented or symptomatic hypoglycemia were found for albiglutide (OR = 1.82; 95% CI, 1.05-3.15), taspoglutide 10 mg (OR = 1.94; 95% CI, 1.03-3.62), once-weekly exenatide (OR = 2.08; 95% CI, 1.14-3.82), dulaglutide 0.75 mg (OR = 2.51; 95% CI, 1.39-4.54) and dulaglutide 1.5 mg (OR = 2.69; 95% CI, 1.51-4.82); no significant differences were found for taspoglutide 20 mg compared with placebo.

Compared with the other treatments, taspoglutide 20 mg revealed the greatest risk for nausea. “The results suggested similar effects of these drugs on several cardiometabolic outcomes, such as BP, blood lipids and C-reactive protein, and a modest increase in heart rate with once-weekly exenatide vs. albiglutide (mean difference, 3 beats/min),” the researchers wrote. “Conversely, we found appreciable differences for HbA1c, [FPG] and body weight, with greater reductions for dulaglutide 1.5 mg, once-weekly exenatide and taspoglutide 20 mg compared with albiglutide and other once-weekly GLP-1 [receptor agonists] at lower doses. We also found differences in the risk for nausea, which was highest for taspoglutide 20 mg and 10 mg and dulaglutide 1.5 mg. Conversely, the risk for documented or symptomatic hypoglycemic did not differ among once-weekly GLP-1 [receptor agonists].”

In an accompanying editorial, Victor M. Montori, MD, MSc, and Rene Rodriguez-Gutierrez, MD, both of the department of medicine at the Mayo Clinic in Rochester, Minnesota, wrote that the top priority may be to address the individual’s situation to find the best antihyperglycemic drug class.

“The next priority should be selecting the best drug within that class, but this can be obfuscated by poor-quality evidence, even when summarized, and by marketing claims that hype trivial differences or mechanistic features of unclear value,” they wrote. “In contrast, drug benefit companies and formulary designers, in their efforts to optimize business outcomes, narrow the options by promoting one product while making competing products unaffordable or unavailable. Clinicians and patients must select the most tolerable and least expensive agent that patients can implement.” – by Amber Cox

Disclosure: Zaccardi and Rodriguez-Gutierrez report no relevant financial disclosures. Montori reports being an employee of the Knowledge and Evaluation Research Unit at Mayo Clinic. Please see the full study for a list of all other authors’ relevant financial disclosures.