TABLE 3.

Metformin versus placebo treatment group effect on the risk (hazard) of diabetes onset before and after adjustment for each time-dependent covariate individually and in combination

	Metformin versus placebo group effect*						Covariate effect†		Percent group R2 explained
Covariate (unit)	Coefficient	SE	Likelihood ratio χ2	P	HR (risk reduction)	R2 (%)	HR	R2 (%)	Univariate (%)	Jointly (%)‡	Jointly (%)§
None	−0.43922	0.09021	23.7041	<0.0001	0.645 (35.5%)	1.150
Body weight (kg)	−0.26896	0.09257	8.4414	0.0037	0.764 (23.6%)	0.409	1.116	4.734	64.4	29.6	7.9
Fasting insulin (pmol/l)	−0.38359	0.09090	17.8070	<0.0001	0.681 (31.9%)	0.863	1.005	2.245	24.9	0.7	0.2
Proinsulin (pmol/l)	−0.33344	0.09175	13.2076	0.0003	0.716 (28.4%)	0.639	1.041	3.671	44.4	8.5	1.0
IGR (pmol/mmol)	−0.43174	0.09032	22.8478	<0.0001	0.649 (35.1%)	1.108	0.987∥	0.616	3.7	2.3	0.2
Leisure activity (MET h/week)	−0.44076	0.09029	23.8320	<0.0001	0.644 (35.6%)	1.156	0.999	0.007	0.0	0.0	0.0
All the above	−0.19843	0.09367	4.4879	0.0341	0.820 (18.0%)	0.217				81.1
Fasting glucose (mmol/l)	−0.20607	0.09172	5.0475	0.0247	0.814 (18.6%)	0.244	2.478	12.993	78.8		17.4
All the above	−0.05508	0.09462	0.3389	0.5605	0.946 (5.4%)	0.016					98.6

^*Models adjusted for baseline age, sex, ethnicity, fasting glucose, 2-h glucose, A1C, recreational activity, percent calories from fat, and the baseline value of all time-dependent covariates.

R² values are based on likelihood ratio tests.

^†Covariate effect adjusted for baseline covariates in the combined groups, not adjusted for treatment group.

^‡Not adjusted for fasting glucose over time.

^§Adjusted for fasting glucose over time. For example, if weight was removed from the model, the remaining covariates, including glucose, would explain 98.6−7.9 (90.7%) of the beneficial metformin effect.

^∥HR for an increase of 10 units.