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Thirty-six patients with type 2 diabetes mellitus (T2DM) were randomized 1:1:1 to receive a once-daily oral dose of placebo or 150 or 300 mg of the dual SGLT1/SGLT2 inhibitor LX4211 for 28 days. Relative to placebo, LX4211 enhanced urinary glucose excretion by inhibiting SGLT2-mediated renal glucose reabsorption; markedly and significantly improved multiple measures of glycemic control, including fasting plasma glucose, oral glucose tolerance, and HbA1c; and significantly lowered serum triglycerides. LX4211 also mediated trends for lower weight, lower blood pressure, and higher glucagon-like peptide-1 levels. In a follow-up single-dose study in 12 patients with T2DM, LX4211 (300 mg) significantly increased glucagon-like peptide-1 and peptide YY levels relative to pretreatment values, probably by delaying SGLT1-mediated intestinal glucose absorption. In both studies, LX4211 was well tolerated without evidence of increased gastrointestinal side effects. These data support further study of LX4211-mediated dual SGLT1/SGLT2 inhibition as a novel mechanism of action in the treatment of T2DM.

Both methods are comparable in identifying at-risk patients under NICE recommendations. A high proportion has risk levels that merits primary CHD prevention. Lowering the risk threshold for statin treatment has a small numerical impact on the whole population.

The purpose of this study was to further validate the Walking Impairment Questionnaire (WIQ) as a self-report tool to aid in the clinical identification of walking ability of patients with peripheral artery disease (PAD). 132 patients with PAD and an ankle brachial index (ABI) ≤0.90 were enrolled; 123 provided complete data for the WIQ and standardized graded treadmill test. The WIQ scores were consistent with reported scores in other studies. The absolute claudication distance (ACD) ranged from 42.3 to 1589.2 meters; the peak walking time (PWT) ranged from 68 to 1800 seconds. Adjusted WIQ scores were positively and moderately associated with the log transformed ACD and PWT (r > .53, P < .001). Based on the area under the curve analysis, an overall WIQ score of 42.5 or less identified low performers (sensitivity 0.90, specificity 0.73); the combined subscale score of distance and stair of 75.5 or more identified high performers (sensitivity 0.41, specificity 0.90). We conclude that WIQ cut-offs appropriately classify walking performance in PAD patients, making this a potentially useful clinical tool. Consideration needs to be given to incorporating a standardized WIQ version into practice guidelines and the use of innovative strategies to facilitate clinical uptake.

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