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The novel investigational sodium-glucose cotransporter 2 inhibitor empagliflozin demonstrated 90 weeks of sustained glycemic control and weight loss in patients with type 2 diabetes. Study researcher Thomas Hach, MD, a senior medical director at Boehringer Ingelheim, spoke withEndocrine Today about the data presented during a late-breaking session here.
“We feel there is an important obligation for us to understand patient benefits: to look at benefit-risks and to really understand which patients will benefit most or where there could possibly be limitations,” Hach said.
In active-control studies, Hach told Endocrine Today that he and colleagues saw comparable efficacy. They conducted a randomized, open-label, 78-week extension study on empagliflozin (Boehringer Ingelheim/Eli Lilly and Company).
They investigated empagliflozin 10 mg (n=81), 25 mg (n=82) or metformin (n=80) as monotherapy, or empagliflozin 10 mg (n=71), 25 mg (n=70) or sitagliptin (n=71; Januvia, Merck) as add-on to metformin in patients with type 2 diabetes who also completed one of two 12-week randomized control trials.
According to 90-week data, adjusted mean changes in HbA1c from baseline were: –0.51% (empagliflozin 10 mg), –0.60% (empagliflozin 25 mg) and –0.64% (metformin); and –0.61% (empagliflozin 10 mg), –0.74% (empagliflozin 25 mg) and –0.45% (sitagliptin).
Further data indicate adjusted mean changes in fasting plasma glucose were: –32.4 mg/dL (empagliflozin 10 mg), –28.1 mg/dL (empagliflozin 25 mg), and –25.9 mg/dL (metformin); –23.3 mg/dL (empagliflozin 10 mg), –31.8 mg/dL (empagliflozin 25 mg), and –11.7 mg/dL (sitagliptin).
Moreover, changes in weight were reported as: –2.1 kg (empagliflozin 10 mg), –1.9 kg (empagliflozin 25 mg), and –0.9 kg (metformin); –2.9 kg (empagliflozin 10 mg), –3.8 k (empagliflozin 25 mg), and –0.6 kg (sitagliptin).
“If I was still in clinical practice, I would look forward to having something new in my armamentarium. Unfortunately, there’s still a huge unmet need in diabetes,” Hach said.
The medication was well tolerated, and the most common adverse events associated with empagliflozin include urinary tract and genital infections. Hach said clinicians should use caution with elderly patients or those with renal impairment because those patients are more susceptible to adverse events.
In March, a new drug application for empagliflozin was submitted to the FDA. Further data will be presented at the American Diabetes Association Scientific Sessions in Chicago next month, Hach said. – by Samantha Costa
For more information:
Ferrannini E. Abstract #1102. Presented at: the AACE Annual Scientific and Clinical Congress; May 1-5, 2013; Phoenix.
Source: Endocrine today
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This study evaluated empagliflozin, an SGLT2 inhibitor, in terms of long-term safety and efficacy in type 2 diabetes patients with vascular disease. There were three arms in this study: empagliflozin 10 mg (n = 2345); empagliflozin 25 mg (n = 2342); and placebo (usual care; n = 2333).
The primary outcomes were CV death, MI, and stroke. The doses showed benefit individually, and, when pooled together, empagliflozin had 14% reduction in the primary outcome (HR, 0.86) and empagliflozin reduced CV death by 38% and total death by 32% in just 3 years. The curves separated early, and they continue to diverge to the end of the study. There was also a 35% reduction in hospitalization for heart failure.
This is the first study of a glucose-lowering medication that has shown a benefit in terms of death rate reduction compared with usual care. There are many theories as to why this might be. For example, the empagliflozin patients did have lower A1cs, reduced blood pressure, and reduced weight and abdominal adiposity. This may have contributed to the benefits; however, such risk factors usually take time to show benefits; yet the curves diverge quickly in this study. Perhaps the SGLT2 is reducing arterial wall stiffness, which, in turn, is reducing sympathetic nerve activation, and thereby reducing albuminuria or glucose variability. As a result, there are fewer ups and downs of glucose and less stress on the heart. No one knows the true answer; but for now, the results speak for themselves.
Guideline writers will have to grapple with how this study will change the order of our recommended treatments and whether this is a drug-specific or a class effect. As more studies are completed in the future, the answers to these questions will become clearer.
For our patients, there is great optimism. On top of statin and ACE/ARB treatments, the total death reduction was 32%. Treating 39 patients would prevent 1 death over a 3-year period. The only real penalty to be paid was a slight increase in yeast infections. There were no bone fractures and no renal failures or complications. However, we must remember that renal function must be good for these medications to work. Almost three-quarters of the patients in this study had eGFR >60 ml/min/1.73m.2
Perhaps empagliflozin will usher in an era when CV protections will be the norm; but, for now, in the right patients, we can postpone death.