Improved Control of Non-insulin-dependent Diabetes Mellitus by Combined Halofenate and Chlorpropamide Therapy

Abstract

Combined halofenate-chlorpropamide was evaluated for the treatment of NIDDM. Four subjects treated with 500 mg/day chlorpropamide were given 500-1000 mg halofenate daily for 48 wk or longer. Fasting plasma glucose fell from 210 +/- 16 (+/- SEM) (11.67 +/- 0.89 mM) to 107 +/- 10 mg/dl (+/- SEM) (5.94 +/- 0.55 mM), P less than 0.005. Twelve additional subjects were entered into a 16-wk double-blind study testing chlorpropamide plus either placebo or halofenate. In the halofenate group, the mean fasting glucose fell from 227 +/- 27 (+/- SEM) (12.61 +/- 1.50 mM) and reached 107 +/- 19 mg/dl (+/- SEM) (5.94 +/- 1.06 mM) during the fourth month, whereas the placebo groups showed a decrease from 242 +/- 22 (+/- SEM) to 208 +/- 29 mg/dl (+/- SEM) (P less than 0.005). In addition, halofenate reduced the height of postprandial glycemic excursions by lowering fasting plasma glucose. When halofenate was used as the only therapy, reduction in fasting plasma glucose was small [179 +/- 12 reduced to 142 +/- 8 mg/dl (+/- SEM); 9.94 +/- 0.67 mM and 7.89 +/- 0.44 mM], P less than 0.05.

Insulin absorption: a major factor in apparent insulin resistance and the control of type 2 diabetes mellitus

“…Anecdotal information from the Texas Diabetes Institute suggests that U500 insulin has a time-course action similar to that of NPH. In agreement with Cusi et al [40], we also note that normalization of fasting morning glucose concentration results in significantly better control of glucose levels throughout the day [47]. It is also relevant that Garvey et al [48] noted that 150 U of regular insulin administered by continuous subcutaneous infusion was necessary to normalize fasting plasma glucose in type 2 diabetic patients.…”

Halofenate Is a Selective Peroxisome Proliferator–Activated Receptor γ Modulator With Antidiabetic Activity

“…While the precise mechanism of halofenate's potentiation of the glycemic effect of sulfonylureas was not understood, it was originally hypothesized that halofenate, being highly plasma protein bound, might dislodge oral hypoglycemic compounds from serum binding proteins, thus increasing their efficacy (8). However, significant decreases in glucose were also observed with halofenate monotherapy (5) showing that halofenate could function independently of sulfonylureas. In analyzing these historical data, we noted that halofenate lowered glucose levels in diabetic, but not normoglycemic, subjects and that the time course of the beneficial glycemic effects was similar to that of the insulin-sensitizing thiazolidinediones (TZDs), which possesses glucose-and insulin-lowering properties mediated via activation of peroxisome proliferator-activated receptor (PPAR)-␥ (9).…”