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Dyslipidemia, often found in type 2 diabetes mellitus (T2DM) patients, plays an important role in the progression of cardiometabolic syndrome. Two essential nutrients, chromium and biotin, may maintain optimal glycemic control. The authors report here a randomized, double-blind placebo-controlled trial (N=348; chromium picolinate and biotin combination [CPB]: 226, placebo: 122; T2DM participants with hemoglobin A1c [HbA1c] ≥7%) evaluating the effects of CPB on lipid and lipoprotein levels. Participants were randomly assigned (2:1 ratio) to receive either CPB (600 μg chromium as chromium picolinate and 2 mg biotin) or a matching placebo once daily for 90 days. Statistical analyses were conducted in all eligible participants. Subsequent supplemental analyses were performed in T2DM participants with hypercholesterolemia (HC) and in those using stable doses of statins. In the primary analysis, CPB lowered HbA1c (P<.05) and glucose (P<.02) significantly compared with the placebo group. No significant changes were observed in other lipid levels. In participants with HC and T2DM, significant changes in total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and atherogenic index were observed in the CPB group (P<.05). Significant decreases in LDL-C, total cholesterol, HbA1c , and very low-density cholesterol levels (P<.05) were observed in the CPB group taking statins. CPB treatment was well tolerated with no adverse effects, dissimilar from those associated with placebo. These data suggest that intervention with CPB improves cardiometabolic risk factors.