Differential changes in serum uric acid concentrations in sibutramine promoted weight loss in diabetes: results from four weeks of the lead-in period of the SCOUT trial

Charlotte Andersson, Peter Weeke, Bente Brendorp, Lars Køber, Emil L Fosbøl, Arya M Sharma, Nick Finer, Ian D Caterson, Richard A Rode, Philip T James, Christian Torp-Pedersen, Charlotte Andersson, Peter Weeke, Bente Brendorp, Lars Køber, Emil L Fosbøl, Arya M Sharma, Nick Finer, Ian D Caterson, Richard A Rode, Philip T James, Christian Torp-Pedersen

Abstract

Background and aims: Elevated levels of serum uric acid are associated with an increased risk of cardiovascular morbidity and mortality. The response of uric acid to weight loss therapy (lifestyle plus sibutramine) in an overweight and obese cardiovascular high risk population was studied.

Methods and results: Data from a four week single-blind lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) study were analyzed. 2584 patients (24%) had diabetes mellitus (DM) only, 1748 (16%) had cardiovascular disease (CVD) only and 6397 (60%) had both DM + CVD. Uric acid concentrations (mean +/- standard deviation) at screening were significantly higher among patients with CVD compared to patients without CVD (p < 0.0001): 369 +/- 86 mumol/L, 374 +/- 98 mumol/L and 342 +/- 87 mumol/L in CVD only, CVD+DM and DM only groups, respectively. During treatment uric acid decreased significantly more in patients without DM (p < 0.0001): -15.0 mumol/L (95% confidence interval -17.7;-12.4), -4.6 mumol/L (-6.2;-3.0), and -6.6 mumol/L (-8.7;-4.5) in CVD only, CVD+DM, and DM only groups, respectively. In patients who failed to lose weight, sibutramine induced lower uric acid levels, but greater weight loss and diabetes were associated with smaller falls in blood uric acid levels; decreasing fasting and urinary glucose concentrations in diabetes were associated with increases in uric acid levels.

Conclusion: A four week daily intake of sibutramine and life style changes was associated with significant reductions in mean uric acid levels. Changes in renal glucose load in diabetes seem to counteract a potential uricosuric effect of sibutramine.

Trial registration: The trial is registered at ClinicalTrial.gov number: NCT00234832.

Figures

Figure 1
Figure 1
Four week change in uric acid concentration, stratified for the presence of only diabetes mellitus (DM), only cardiovascular disease (CVD) or both (p-value for changes <0.0001 in respectively group). Error bars illustrate 95% confidence interval.
Figure 2
Figure 2
Mean change in uric acid concentration, according to four week weight change (left) and four week mean change in fasting serum glucose (FSG, right) in patients with diabetes. "Numbers" refers to the numbers of patients with available values on the uric acid change in the respective group. The mean uric acid concentration change was found to differ in both the groups of weight change and the groups of FSG change (p < 0.0001 in both analyses). Error bars illustrate 95% confidence interval.
Figure 3
Figure 3
Mean change in uric acid concentration, according to four week weight change (left) and four week mean change in fasting serum glucose (FSG, right) in patients without diabetes. "Numbers" refers to the numbers of patients with available values on the uric acid change in the respective group. No difference was found in mean uric acid concentration change between the weight change groups (p = 0.3). The mean uric acid concentration change was found to differ over the groups of FSG change (p = 0.0004). Error bars illustrate the 95% confidence interval.
Figure 4
Figure 4
Mean change in uric acid concentration for patients with diabetes, according to four week change in urinary glucose, estimated by dip stick. The dip stick scale ranged between "negative", "trace", "1+", "2+" and "3+" for glucose content. FSG = fasting serum glucose. Error bars illustrate 95% confidence interval. Variables in table are presented as means (± standard deviation). Analysis for patients without diabetes was not performed, since 99% of the patients had a negative dip stick at screening, and 99% of the patients were found to have no change in glucose dip stick.

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