Prevention of Type 2 Diabetes With Troglitazone in the Diabetes Prevention Program

Pharmacology & Therapeutics

Address correspondence and reprint requests to The Biostatistics Center, George Washington University, 6110 Executive Blvd., Suite 750, Rockville, MD 20852. E-mail: dppmail{at}biostat.bsc.gwu.edu

Article Figures & Tables

Download figure
Open in new tab
Download powerpoint
FIG. 1.
Mean values of body weight, waist circumference, and FPG and 2-h postload glucose concentrations in response to treatment. Sample sizes are shown in Table 2.
Download figure
Open in new tab
Download powerpoint
FIG. 2.
A: Cumulative incidence of diabetes during the time when troglitazone was used, according to treatment assignment. B: Diabetes incidence rates (cases/100 person-years) with 95% CIs during the time when troglitazone was used, according to treatment assignment.
Download figure
Open in new tab
Download powerpoint
FIG. 3.
A: Cumulative incidence of diabetes (%) from date of randomization in participants assigned to placebo or troglitazone. B: Cumulative incidence of diabetes (%) from date of discontinuation of troglitazone (4 June 1998) in participants assigned to placebo or troglitazone. C: Diabetes incidence rates (cases/100 person-years) from date of randomization, showing the date of discontinuation of troglitazone (4 June 1998), in participants assigned to placebo or troglitazone.

TABLE 2

Body weight, waist circumference, and FPG and 2-h postload plasma glucose concentrations

Variable	Time (years)	Placebo			Metformin			Troglitazone			ILS
Variable	Time (years)			n	Mean	n	Mean	n	Mean	n	Mean
Body weight (kg)	0.0	582	94.6	587	94.5	585	93.3	589	95.5
	0.5	384	94.5	389	92.8	378	95.2	386	88.1
	1.0	182	95.3	172	93.3	196	97.0	191	89.7
	1.5	58	97.6	59	94.3	72	98.0	53	91.1
Waist circumference (cm)	0.0	582	105.6	586	105.0	585	104.3	588	106.1
	1.0	180	105.1	172	104.4	197	105.7	191	100.4
FPG (mmol/l)	0.0	582	5.96	587	5.96	585	5.96	589	5.98
	0.5	388	5.97	394	5.72	383	5.63	388	5.71
	1.0	182	6.00	172	5.80	197	5.66	190	5.75
	1.5	58	6.27	61	5.88	72	5.74	54	6.00
2-h plasma glucose (mmol/l)	0.0	582	9.22	587	9.19	585	9.18	589	9.19
	1.0	174	8.79	172	8.81	196	8.03	188	7.86

None of the variables differed significantly between treatment groups at baseline (time = 0). By repeated-measures ANOVA, the troglitazone group differed significantly from each of the others (P < 0.05 adjusted for three comparisons) for body weight and FPG. It differed significantly from the ILS group for waist circumference and from the placebo and metformin groups in 2-h plasma glucose. n, number of participants with the measurement at each time point. Conversion of units for glucose: 1 mg/dl = 0.05551 mmol/l.

TABLE 3

Baseline and follow-up median values of serum insulin-related variables by treatment over time

Variable	Time (years)	Placebo	Metformin	Troglitazone	ILS	P difference among four treatments (Kruskal-Wallis)	Placebo vs. troglitazone	Metformin vs. troglitazone	ILS vs. troglitazone
n		172	164	187	183
Fasting insulin (pmol/l)	0	144	138	132	132	0.58	—	—	—
	1	132	111	90	102	<0.01	†	†	—
	Δ	—	*	*	*	<0.01	†	—	—
30-min insulin (pmol/l)	0	513	498	498	474	0.72	—	—	—
	1	522	447	402	408	<0.01	†	†	—
	Δ	—	*	*	—	<0.01	†	†	—
Sensitivity [1/fasting insulin 1,000/(pmol/l)]	0	6.94	7.25	7.58	7.58	0.58	—	—	—
Sensitivity [1/fasting insulin 1,000/(pmol/l)]		1	7.58	9.02	11.11	9.80	<0.01	†	†	—
	Δ	—	*	*	*	<0.01	†	—	—
Sensitivity {ISI 10,000/ [(pmol/l) × (mmol/l)]}	0	11.8	12.0	12.3	12.5	0.64	—	—	—
Sensitivity {ISI 10,000/ [(pmol/l) × (mmol/l)]}		1	13.2	15.4	19.9	17.0	<0.01	†	†	—
	Δ	—	*	*	*	<0.01	†	†	—
Secretion {CIR (pmol/l)/ [(mmol/l)²]}	0	10.1	9.05	9.58	9.06	0.19	—	—	—
Secretion {CIR (pmol/l)/ [(mmol/l)²]}		1	10.3	8.47	10.15	8.34	0.05	—	—	—
	Δ	—	—	—	—	0.99	—	—	—
Secretion [IGR (pmol/l)/ (mmol/l)]	0	116.4	102.1	108.1	101.5	0.24	—	—	—
Secretion [IGR (pmol/l)/ (mmol/l)]		1	109.1	91.1	103.2	91.4	0.03	—	—	—
	Δ	—	—	—	—	0.43	—	—	—

*
* P < 0.05 for difference from baseline to 1 year (signed-rank test).
†
† P < 0.05 compared with troglitazone (Wilcoxon test, adjusted for multiple comparisons, i.e., unadjusted P < 0.0167). Dash indicates no significant difference; n, number of participants with both baseline and 1-year measurements; Δ, test for difference between baseline and 1 year. Conversion of units: for insulin, 1 μU/ml = 6.0 pmol/l; for glucose, 1 mg/dl = 0.05551 mmol/l.

TABLE 4

Adverse events by treatment assignment

Event	Placebo	Metformin	Troglitazone	ILS
n	582	587	585	589
CHF	0 (0.0)	1 (0.2)	0 (0.0)	1 (0.2)
MI	2 (0.3)	0 (0.0)	0 (0.0)	2 (0.3)
Anemia	7 (1.2)	5 (0.9)	7 (1.2)	4 (0.7)
Edema	31 (5.3)	8 (1.4)	27 (4.6)	26 (4.4)
LFT ≥3	21 (3.6)	18 (3.1)	25 (4.3)	NA
LFT ≥10	1 (0.2)	0 (0.0)	7 (1.2)	NA

Data are n (%) of individuals in each randomization group experiencing at least one adverse event of the type specified. Liver function tests were not measured on the same schedule in the ILS group. CHF, congestive heart failure; MI, myocardial infarction; LFT ≥3, liver function test (either alanine aminotransferase or aspartate aminotransferase) ≥3 times the upper limit of normal; LFT ≥10, liver function test (either alanine aminotransferase or aspartate aminotransferase) ≥10 times the upper limit of normal; NA, not applicable.