Long-term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus.
OBJECTIVE
To evaluate the long-term safety and efficacy of glyburide versus pioglitazone in patients with a recent diagnosis of type 2 diabetes mellitus.


METHODS
Prospective, randomized, multicenter, double-blind trial with a 16-week titration period and a 40-week maintenance period.


METHODS
Sixty-five investigative sites in the United States and Puerto Rico.


METHODS
Five hundred two subjects with a recent diagnosis of type 2 diabetes that was unsuccessfully treated with diet and exercise were randomly assigned to study treatment. Of the 251 patients in each treatment group, 128 (51.0%) glyburide-treated patients and 134 (53.4%) pioglitazone-treated patients completed the study.


METHODS
Dosages of randomly assigned glyburide and pioglitazone were titrated every 4 weeks for 16 weeks in 5-mg/day and 15-mg/day increments, respectively, until a fasting plasma glucose level between 69 and 141 mg/dl was achieved. The optimized regimen was maintained during the subsequent 40-week double-blind phase.


RESULTS
At week 56, glyburide and pioglitazone improved glucose control comparably (change in hemoglobin A(1c) -2.02% and -2.07%, respectively, p=0.669). Withdrawal due to lack of efficacy or adverse events occurred more frequently with glyburide (20.8%) than pioglitazone (12.8%, p<0.032). Significantly higher percentages of glyburide- than pioglitazone-treated patients had a hypoglycemic (24.3% vs 4.4%, p=0.0001) or cardiac (8.8% vs 4.4%, p=0.0478) event. Edema (4.8% vs 7.9%, p=0.1443) and weight gain (4.4% vs 4.0%, p=0.8238) did not differ significantly between the glyburide and pioglitazone groups. Only a few patients discontinued study drug because of weight gain (one glyburide, one pioglitazone), edema (one pioglitazone), or a cardiac event (two glyburide).


CONCLUSIONS
With long-term treatment, both glyburide and pioglitazone resulted in comparable glycemic control; however, pioglitazone was associated with less hypoglycemia and fewer withdrawals due to lack of efficacy or adverse events.
Jain
Rajeev
R
Endocrinology Division, Advanced Healthcare, SC, Milwaukee, Wisconsin, USA.
Osei
Kwame
K
Kupfer
Stuart
S
Perez
Alfonso T
AT
Zhang
Jeff
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D005905:Glyburide / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D018570:Risk Assessment; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D005905:Glyburide; D000077205:Pioglitazone