Category: GLP-1

GLP-1 Receptor Agonists and SGLT-2 Inhibitors: A Dynamic Duo?

September 23, 2016

First clinical trial to study GLP-1 receptor agonist and SGLT-2 inhibitor combination shows positive results

Experts have speculated that combination GLP-1 receptor agonist and SGLT-2 inhibitor therapy may have synergistic, beneficial effects in the treatment of type 2 diabetes. Now there are data to support this, as results of DURATION-8, the first clinical trial to study the combination as an addition to standard-of-care therapy, were recently announced at the European Association for the Study of Diabetes (EASD) 2016 Annual Meeting and published in the Lancet Diabetes and Endocrinology. Read more

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Another GLP-1 Agonist, Semaglutide, Shows Cardiovascular Benefit in CV Outcomes Trial SUSTAIN 6

The GLP-1 agonist semaglutide is the latest diabetes therapy to show cardiovascular benefit in a CV outcomes trial, demonstrating a reduction in the risk of major adverse cardiovascular events compared with usual care.

SUSTAIN 6 included 3,297 patients with type 2 diabetes on a standard diabetes care regimen randomized to once-weekly semaglutide or placebo for 2.1 years. Among those who received semaglutide, the rate of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was lowered to 6.6% compared with 8.9% in the placebo group receiving usual care. Researcher Dr. Steven Marso of HCA Midwest Health Research Medical Center in Kansas City, MO, commented that this lower risk was largely driven by a significant (39%) decrease in the rate of nonfatal stroke and a nonsignificant (26%) decrease in nonfatal myocardial infarction. No significant difference in the rate of cardiovascular death was observed. Read more

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GLP-1 Receptor Agonist Lixisenatide Approved by US FDA

The GLP-1 receptor agonist lixisenatide has received US FDA approval for the treatment of adults with type 2 diabetes as an adjunct to diet and exercise. Approval was based on 11 clinical trials that evaluated more than 11,000 patients, including a cardiovascular outcomes trial, ELIXA, that showed no increase in adverse cardiovascular events. Efficacy studies showed lixisenatide improved HbA1c when used alone and in combination with other therapies, including sulfonylureas, metformin, pioglitazone, and basal insulin.

Lixisenatide will be available in a disposable prefilled pen.

Reference: Medscape Medical News. GLP-1 agonist lixisenatide okayed for type 2 diabetes in US.

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GLP-1 Agonist Liraglutide Shown to Significantly Reduce the Risk of Major Adverse Cardiovascular Events in LEADER

Results of the cardiovascular outcomes LEADER trial have shown the GLP-1 agonist liraglutide to significantly reduce the risk of major adverse cardiovascular events. The trial, which began in 2010, included 9340 high-risk adults with type 2 diabetes who were randomized to either placebo or liraglutide along with standard treatment. The primary endpoint of LEADER was defined as the composite outcome of the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The superior reduction of major adverse cardiovascular events demonstrated by liraglutide was derived from all three components of the endpoint.

Last year, the SGLT-2 inhibitor empagliflozin was the first glucose-lowering agent to demonstrate cardiovascular risk reduction in a CV outcomes trial. Other CV outcomes trials have shown neutral results with regard to cardiovascular risk reduction or have raised concern about a potentially increased risk for heart failure.

Full data from LEADER are expected to be presented at the American Diabetes Association’s Annual Scientific Sessions in June. For additional commentary on LEADER read more here.

Perspective on these results will also be shared by our expert faculty during “The Shifting Sands of CVD Prevention in Diabetes––A New Outlook for Patient Care,” during The Best of the CMHC Regional Conference Series, in Atlanta on May 7, 2016 and in Chicago on June 18, 2016, and at the 11th Annual CMHC in Boston, October 5-8, 2016.

Medscape. Top-line data show CV benefit for liraglutide in type 2 diabetes.

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Lixisenatide Proves Safety in ELIXA While Liraglutide Shows Greater HbA1c Reduction Compared with SGLT-2 Inhibitors

CV outcomes data from the ELIXA trial have been published in the New England Journal of Medicine for the as-yet FDA unapproved GLP-1 agonist lixisenatide, and have shown no increase or decrease in the rate of major cardiovascular events in patients with acute coronary syndrome. Read more here.

Meanwhile, findings from a recent meta-analysis have shown that among people with type 2 diabetes the GLP-1 agonist liraglutide provided greater HbA1c reductions compared with SGLT-2 inhibitors. Comprising the meta-analysis were 17 randomized controlled trials that included patients with type 2 diabetes inadequately controlled with metformin alone or in combination with sulfonylurea, DPP-4 inhibitors, or thiazolidinedione. Liraglutide was also associated with an improved likelihood of achieving glycemic goals compared with SGLT-2 inhibitors. Read more from a press release on the meta-analysis here.

Pfeffer MA et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med. 2015;373:2247-2257.

Lorenzi M et al. Liraglutide vs SGLT-2 inhibitors in people with type 2 diabetes: a network meta-analysis. Presented at 23rd World Diabetes Congress, Vancouver, BC, Canada; 30 November – 4 December 2015. Abstract number 0226-P.

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GLP-1 Agonist Liraglutide Significantly Decreases CV Risk and Mortality: Full Results From LEADER Presented

The GLP-1 agonist liraglutide has been shown to significantly decrease the risk of major cardiovascular events and death from any cause over a 3-year period: a 13% relative risk reduction, when compared with placebo as add-on therapy, according to results from the LEADER trial presented at the annual meeting of the American Diabetes Association (ADA). Other findings include a 15% reduction in all-cause mortality and a 22% reduction in cardiovascular death during follow-up. Therapy with liraglutide was also associated with a significant 22% reduction in the time to a first renal event, which was a secondary endpoint.

More than 9000 patients were enrolled in LEADER, with more than 4400 assigned to liraglutide plus standard of care and the remaining assigned to placebo plus standard of care. Patients were treated for a median of 3.8 years.

CMHC Chair Robert Eckel, MD, who moderated the ADA press conference during which results were reported, indicated although LEADER is a complicated study, it may have an impact on practice. Speaking about the treatment algorithm when patients don’t reach HbA1c goals on metformin, Dr. Eckel said, “With EMPA-REG, published a year ago, and now with LEADER, we have to think beyond metformin as to what that second drug of choice might be. With LEADER we already have a hint that there may be another drug in this class that appears to be beneficial.”

For more insight and expert perspective, plan to attend the 11th Annual Cardiometabolic Health Congress, taking place this October 5-8, 2016 in Boston, MA, which will further explore the clinical implications of the results of CV outcomes trials including LEADER and EMPA-REG.


Marso et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. June 13, 2016DOI: 10.1056/NEJMoa1603827.

MedPage Today. ADA: Liraglutide reduces risk risk of heart events. June 13, 2016.

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