. 2022 Apr;17(4):507–517. doi: 10.2215/CJN.11260821

Table 4.

Change in various study parameters

End Points	Mean Value			Changes Compared with Placebo
	Hydrochlorothiazide	Placebo	Metformin	Hydrochlorothiazide		Metformin
	Hydrochlorothiazide	Placebo	Metformin	Mean (95% Confidence Interval)	P Value	Mean (95% Confidence Interval)	P Value
Primary end point
Absolute urine volume, L/24 h	5.13±1.46	6.34±1.62	5.40±1.51	–1.2 (–1.7 to –0.8)^a	<0.001^a	–0.9 (–1.4 to –0.5)^a	<0.001^a
Secondary end points
Plasma copeptin, pmol/L	20±7	26±7	28±8	–5.6 (–9.0 to –2.3)^a	0.001^a	1.6 (–1.7 to 5.0)	0.30
Measured GFR, ml/min per 1.73 m²	51±10	55±12	54±11	–3.8 (–5.5 to –2.2)^a	<0.001^a	−1.1 (–2.7 to 0.5)	0.20
Post hoc exploratory end points
Free water clearance, L/24 h	1.60±1.25	2.88±1.76	2.13±1.42	–1.3 (–1.7 to –0.9)^a	<0.001^a	–0.7 (–1.1 to –0.3)^a	<0.001^a
Plasma osmolality, mOsm/L	288±4	292±5	289±4	–3.4 (–5.0 to –1.7)^a	<0.001^a	–2.1 (–3.8 to –0.5)^a	0.001^a
Plasma sodium, mEq/L	139±2	141±2	140±2	–1.7 (–2.9 to –0.4)^a	0.008^a	−0.6 (–1.9 to 0.6)	0.30
Plasma NTproBNP, ng/L	43±23	82±52	53±28	–40 (–57 to –23)^a	<0.001^a	–27 (–45 to –9)^a	0.003^a
Urine osmolality, mOsm/L	204±54	167±64	180±60	38 (27 to 49)^a	<0.001^a	13 (2 to 24)^a	0.03^a
Osmole excretion, mOsm/24 h	1020±307	1013±296	947±311	6 (–68 to 79)	0.90	−64 (–137 to 9)	0.09
FeLithium, %	18.4±3.4	21.8±3.4	19.3±5.4	–3.5 (–5.4 to –1.6)^a	<0.001^a	–2.4 (–4.4 to –0.5)^a	0.01^a
Aquaporin-2 excretion, g/24 h	4.67±4.50	5.19±6.60	6.78±8.42	0.2 (–0.6 to 1.0)	0.60	0.8 (–0.1 to 1.6)	0.07
Weight, kg	90.6±18	91.6±18	91.2±18	–1.0 (–1.5 to –0.4)^a	<0.001^a	−0.4 (–0.9 to 0.1)	0.10
Systolic BP, mm Hg	117±11	122±9	120±12	–5.6 (–9.8 to –1.4)^a	0.009^a	−2.1 (–6.2 to 2.1)	0.30
Extracellular volume, L	14.5±3.4	15.1±2.9	14.7±2.8	−0.6 (–1.2 to 0.0)	0.05	−0.4 (–1.0 to 0.2)	0.20

Variables are presented as mean±SD. Changes were compared with placebo using generalized linear mixed models. Other end points were ad hoc and not prespecified; results should be interpreted as hypothesis generating rather than hypothesis testing. NTproBNP, N-terminal pro-brain natriuretic peptide; FeLithium, fractional lithium excretion.

P<0.05.