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Lipid-lowering drug improves glucose control in type 2 diabetes
Plasma apolipoprotein C-III and triglycerides were reduced with volanesorsen, a second-generation antisense inhibitor of apolipoprotein C-III, according to study findings published in Diabetes Care.
After short-term treatment, patients had improved glucose disposal, insulin sensitivity and integrative markers of diabetes, according to the researchers.
“These results prove volanesorsen to be an effective treatment method for improving insulin sensitivity, but what’s most interesting and perhaps most encouraging, is that this drug also significantly improved patients’ HbA1c levels,” Richard Dunbar, MD, assistant professor of cardiovascular medicine at the Perelman School of Medicine, University of Pennsylvania, said in a press release. “In most cases, it takes many months of therapy to improve HbA1c, so to move the needle so significantly in a fairly short time is very promising. Scientifically, these results provide important proof that profoundly lowering triglycerides improves insulin sensitivity. And clinically, the results go a step further and show that doing so improved the underlying metabolic problems enough to actually improve diabetes.”
Dunbar, Andres Digenio, MD, PhD, vice president of clinical development at Akcea Therapeutics Inc., developer of volanesorsen, and colleagues evaluated 15 adults (mean age, 56.5 years; 73% women) with type 2 diabetes (HbA1c > 7.5%) and hypertriglyceridemia (triglycerides, 200 mg/dL to 500 mg/dL) to determine the effect of volanesorsen on triglyceride levels and insulin resistance. Participants were randomly assigned to volanesorsen 300 mg (n = 10) or placebo (n = 5) for a total of 15 subcutaneous weekly doses.
Compared with placebo, volanesorsen reduced ApoC-III (–87.5%; P = .019) and triglycerides (–69.1%; P = .019) and increased HDL (42.5%; P = .034) from baseline after 13 weeks.
Whole-body insulin sensitivity improved by 57% with volanesorsen compared with placebo. A strong association was found between enhanced insulin sensitivity and plasma ApoC-III (P = .03) and triglyceride (P = .01) suppression.
One week after the last dose, volanesorsen lowered glycated albumin (P = .034) and fructosamine (P = .045) and lowered HbA1c (P = .025) 3 months after the last dose.
“While we were able to determine the effectiveness of this medication in a very specific group of diabetic patients, it will be important to evaluate this drug in a broader diabetic population,” Dunbar said in the release. “The next phase will be to determine clinical success in patients with type 2 diabetes on the whole range of diabetic medications or perhaps with less severe lipid problems. It will also be important to conduct longer studies, as glucose control may improve even further with longer exposures to the drug.” – by Amber Cox
Disclosure: Digenio reports being an employee of Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals. Dunbar reports being an investigator for an ongoing volanesorsen clinical trial. Please see the full study for a list of all other authors’ relevant financial disclosures.