#Fluid retention meaning trial#

In general, improvement in glycemic control with decreased glycosuria and caloric retention may result in increased weight. The weight gain associated with the use of TZDs is probably due to several interacting factors. Thus, the weight gain associated with TZD use seems to be dose dependent, although in one 4-month randomized open-label trial, similar increases in body weight ( ∼2 kg) were seen across the entire dose ranges of rosiglitazone (2 to 8 mg/day) and pioglitazone (15 to 45 mg/day) ( 16). Food and Drug Administration in support of pioglitazone did not include data on weight gain at its highest recommended daily dose of 45 mg when coadministered with sulfonylurea, metformin, or insulin, although these data have recently been cited.

#Fluid retention meaning trial#

In contrast to trials with rosiglitazone, which included changes in weight gain at rosiglitazone’s highest recommended daily dose (8 mg), the clinical trial data submitted to the U.S. Median weight gains of 2.3 and 3.6 kg occurred when pioglitazone at 15 and 30 mg daily was added to insulin. Compared with placebo, pioglitazone monotherapy caused median weight gains of 0.9, 1.0, and 2.6 kg at the 15-, 30-, and 45-mg daily doses, respectively ( 5). Similar increases have been observed with pioglitazone, either as monotherapy or in combination with other hypoglycemic therapies, although the duration of treatment was not identical ( 15). After 6 months of treatment, weight gains of 4.1 kg and 5.4 kg were encountered when rosiglitazone, at the 4-mg and 8-mg daily doses, respectively, was added to insulin (mean dose 70 units/day), compared with a weight gain of ∼1 kg in patients treated with insulin alone ( 4). When added to insulin therapy, however, weight gain may be more dramatic. Similar weight gain has been observed when rosiglitazone is added to metformin. When coadministered with a sulfonylurea in a 26-week study, rosiglitazone at 4 mg/day was associated with a 1.8-kg weight gain compared with sulfonylurea alone. In a 52-week study comparing rosiglitazone to a sulfonylurea (glyburide, median dose 7.5 mg/day), a mean weight gain of 1.9 kg was observed in both the sulfonylurea group and the rosiglitazone group at the 4-mg daily dose, and a 2.9-kg weight gain was observed at the rosiglitazone 8-mg daily dose ( 4). This statement is a summary of the workgroup’s findings and recommendations. For these reasons, the American Diabetes Association and the American Heart Association assembled a workgroup to evaluate the use of TZDs in patients with preexisting heart disease and in those who develop edema or unexpected weight gain during the course of TZD therapy.

Because edema is a more frequent side effect of TZD therapy and by itself is often a perplexing clinical dilemma with multiple causes ( 14), clinicians may need guidance when edema (or unexpected weight gain) is encountered in a patient on a TZD. At present, there are no guidelines on the use of TZDs in patients with diabetes who have any degree of heart disease or for those already on a TZD who develop CHF. The package inserts for both rosiglitazone and pioglitazone indicate that patients with more advanced heart disease (class III or IV) were excluded in premarketing clinical trials, and hence, these drugs are not recommended in such patients. Patients with type 2 diabetes who have significant underlying asymptomatic heart disease may also be prescribed these drugs, even though their safety in such patients has not been fully established.

Clinicians should be cognizant that CHF or left ventricular dysfunction (systolic or diastolic) may be present at the time TZDs are first prescribed or may occur over time during TZD treatment. For example, an analysis of a large number ( n = 9,591) of registrants with type 2 diabetes in the Kaiser Permanente Northwest Division demonstrated that CHF was present in 11.8% of diabetic subjects at baseline, and an additional 7.7% developed CHF over a 30-month follow-up period ( 13). Therefore, diabetes is a strong and independent risk factor for CHF. Diabetes also may affect cardiac structure and systolic or diastolic function, independent of other established risk factors for CHF, as a result of diabetic cardiomyopathy ( 10– 12). These risk factors act synergistically in diabetes to increase the risk for CHF. Risk factors for CHF, such as coronary artery disease and hypertension, frequently occur in patients with diabetes ( 1, 9).