A Randomized Trial of Rosiglitazone Therapy in Patients With Inadequately Controlled Insulin-Treated Type 2 Diabetes
- Philip Raskin, MD1,
- Marc Rendell, MD2,
- Matthew C. Riddle, MD3,
- Jo F. Dole, PHD4,
- Martin I. Freed, MD4,
- Julio Rosenstock, MD5 and
- For the Rosiglitazone Clinical Trials Study Group
- 1University of Texas Southwestern Medical Center at Dallas, Dallas, Texas
- 2Creighton University, Omaha, Nebraska
- 3Oregon Health Sciences University, Portland, Oregon
- 4SmithKline Beecham Pharmaceuticals, Collegeville, Pennsylvania
- 5Dallas Diabetes and Endocrine Center, Dallas, Texas
OBJECTIVE—To determine the efficacy and safety of rosiglitazone (RSG) when added to insulin in the treatment of type 2 diabetic patients who are inadequately controlled on insulin monotherapy.
RESEARCH DESIGN AND METHODS—After 8 weeks of insulin standardization and placebo (PBO) run-in, 319 type 2 diabetic patients with mean baseline HbA1c ≥7.5% (8.9 ± 1.1 to 9.1 ± 1.3) on twice-daily insulin therapy (total daily dose ≥30 U) were randomized to 26 weeks of additional treatment with RSG (4 or 8 mg daily) or PBO. Insulin dose could be down- titrated only for safety reasons. The primary end point was reduction of HbA1c from baseline.
RESULTS—RSG 4 and 8 mg daily significantly improved glycemic control, which was unchanged on PBO. By intent-to-treat analysis, treatment with RSG 8 mg plus insulin resulted in a mean reduction from baseline in HbA1c of 1.2% (P < 0.0001), despite a 12% mean reduction of insulin dosage. Over 50% of subjects treated daily with RSG 8 mg plus insulin had a reduction of HbA1c ≥1.0%. Neither total:HDL cholesterol nor LDL:HDL cholesterol ratios significantly changed with RSG treatment. Serious adverse events did not differ among groups.
CONCLUSIONS—The addition of RSG to insulin treatment results in significant improvement in glycemic control and is generally well tolerated.
- AE, adverse event
- ALT, alanine aminotransferase
- AST, aspartate aminotransferase
- BP, blood pressure
- CHF, congestive heart failure
- FPG, fasting plasma glucose
- I, insulin
- PBO, placebo
- RSG, rosiglitazone
- TZD, thiazolidinedione
- UKPDS, U.K. Prospective Diabetes Study
- WHR, waist-to-hip ratio
Address correspondence and reprint requests to Philip Raskin, MD, University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX. E-mail:.
Received for publication 7 September 2000 and accepted in revised form 30 January 2001.
P.R. has received honoraria for speaking engagements and consultations and has received research grant support from SmithKline Beecham. M.R. has received honoraria or consulting fees and has received grant/research support from SmithKline Beecham. M.C.R. has received honoraria or consulting fees from Amylin, Aventis, Ortho-McNeil, Novo-Nordisk, Parke-Davis, Pfizer, and SmithKline Beecham and has received grant/research support from Bristol-Myers Squibb, Aventis, Parke-Davis, Pharmacia and Upjohn, Pfizer, SmithKline Beecham, Novo Nordisk, and Merk. J.R. owns stock in and has received honoraria or consulting fees and grant/research support from SmithKline Beecham.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.