Synopsis: In type 2 diabetics (T2D) with normal renal function, serum phosphorus (P) concentrations have been reported as a strong, independent predictor of cardiovascular disease mortality. Calcium salts, despite their efficacy as a phosphate-lowering treatment in advanced chronic kidney disease (CKD), can enhance vascular calcification, which may be particularly problematic in T2D. Uncontrolled studies and two small, limited duration placebo-controlled trials indicate that niacin compounds lower serum P concentrations in patients with end-stage renal disease (ie, stage 5 CKD, an estimated glomerular filtration rate [eGFR] < 15 ml/min/1.73 m2). Such data are complemented by mechanistic studies indicating that niacin causes direct inhibition of sodium-dependent, active intestinal phosphate transport.
Purpose: We expanded upon these observations by evaluating the impact of extended-release niacin (ERN), given in fixed-dose combination with laropiprant (L), a specific inhbitor of prostaglandin-mediated, niacin-induced flushing, versus placebo (PBO), on serum P concentration in a randomized, 36-week trial of dyslipidemic patients with T2D (baseline creatinine <2 mg/dL).
Methods: Serum P was analyzed in a subset of the total patients (n = 446 ERN-L; n = 339 PBO) whose baseline serum P was >3.5 mg/dL (n = 224 ERN-L; n = 169 PBO), at weeks 0, 4, 8, 12, 18, 24, 30, and 36. Their estimated glomerular filtration rate (eGFR) ranged from 36 to 184, with 62 (15.8%) having an eGFR <60 (ie, CKD ≥ stage 3; 30–59). Patients received one tablet daily of ERN-L (ERN 1 g/L 20 mg) for 4 weeks, and two tablets once daily, thereafter, or matched PBO.
Results: Post-hoc repeated measures analysis in this subgroup demonstrated that ERN-L lowered serum P concentrations by 0.39 mg/dL (95% confidence interval, −0.46, −0.31; P < .001), relative to PBO, expressed as the treatment difference between the week 12 and 36 average changes from baseline (baseline means of 3.98 and 3.97 mg/dL for ERN-L and PBO, respectively).
Conclusions: These data confirm that niacin's P-lowering effects—which may have therapeutic implications for the management of hyperphosphatemia in renal disease—extend across a broad spectrum of renal function (eGFR) in T2D without stage 4 or 5 CKD (an eGFR ≥30).
Figure. Serum phosphorus concentrations by treatment group at baseline (week 0), and weeks 4, 8, 12, 18, 24, 30, and 36, among those with a baseline serum phosphorus of >3.5 mg/dL. ERN-L, extended-release niacin + laropiprant.
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