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Acipimox added to Farxiga improves beta-cell function in men with type 2 diabetes
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Men with type 2 diabetes who received acipimox as an add-on to 3 weeks of Farxiga therapy saw improved beta-cell function and beta-cell sensitivity to glucose beyond Farxiga alone; however, the addition of the lipolysis inhibitor did not cause further improvement in insulin sensitivity, according to research in The Journal of Clinical Endocrinology & Metabolism.
Aurora Merovci, MD, of the division of diabetes at the University of Texas Health Science Center at San Antonio, and colleagues analyzed data from 14 men with type 2 diabetes (mean age, 50 years; mean BMI, 32.7 kg/m²; mean HbA1c, 8.5%; mean diabetes duration, 6.3 years) treated with metformin (n = 9) or metformin plus sulfonylurea (n = 5). All participants underwent a 2-hour, 75-g oral glucose tolerance test and a 4-hour hyperinsulinemic-euglycemic clamp at baseline. Researchers assigned 10 mg Farxiga (dapagliflozin, AstraZeneca) daily for 3 weeks. At the beginning of week 3, researchers assigned 250 mg acipimox four times daily in addition to dapagliflozin therapy. The OGTT and insulin clamp were repeated on days 13, 14, 21 and 22.
Dapagliflozin lowered the plasma glucose concentration by 35 mg/dL from baseline to week 2 (from 186 mg/dL to 151 mg/dL; P < .01) but did not affect fasting plasma free fatty acid concentration (0.52 mM vs. 0.51 mM). Acipimox further decreased the fasting plasma glucose concentration by 20 mg/dL (P = .01) and decreased fasting plasma free fatty acid concentration by 0.15 mM (P < .05).
Insulin-mediated glucose disposal increased at week 2 compared with baseline (from 4.48 mg/kg/min to 5.3 mg/kg/min; P < .05), but did not increase further after the addition of acipimox, according to researchers. Glucose-stimulated insulin secretion at week 2 also significantly increased compared with baseline, and increased further with the addition of acipimox.
“Surprisingly, acipimox failed to cause a further improvement in insulin sensitivity when added to dapagliflozin in [type 2 diabetes] individuals,” the researchers wrote. “It is possible that the intramyocellular concentration of toxic lipid metabolites declined with dapagliflozin treatment. This could explain why acipimox, when added to dapagliflozin, failed to further increase insulin-stimulated glucose disposal.” – by Regina Schaffer
Disclosure: One of the researchers reports serving on advisory boards, receiving research support and/or speaker’s fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Lexicon, Novo Nordisk and Takeda. The other researchers report no relevant financial disclosures.
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