Effects of Metformin Added to Insulin in Adolescents with Type 1 Diabetes: An Exploratory Crossover Randomized Trial

Table 2

Effects of metformin add-on insulin vs. insulin therapy alone on metabolic parameters, glucose variability, and heart rate variability.

	Nonmetformin		Metformin		Treatment effect
	Before	After 24 weeks	Before	After 24 weeks	Non-metformin	Metformin	Difference (95% CI)
Metabolic parameters
	17	15	16	15	15	15
HbA1c (%)							0.28 (-0.39, 0.95)	0.40
FPG (mmol/L)							-2.66 (-5.68, 0.35)	0.08
SBP (mmHg)							0.2(-6.2, 6.5)	0.96
DBP (mmHg)							-0.3(-5.6, 5.0)	0.90
BMI (kg/m^2)							-0.46 (-1.38, 0.47)	0.32
TC (mmol/L)							0.16 (-0.91, 0.17)	0.56
LDL-C (mmol/L)	2.62 (2.21, 3.25)	2.42 (2.11, 2.93)	2.25 (2.04, 2.71)	2.59 (2.38, 3.11)	-0.06 (-0.39, 0.33)	0.02 (-0.03, 0.40)	–	0.16
HDL-C (mmol/L)							0.11 (-0.05, 0.27)	0.16
TG (mmol/L)	069 (0.59, 0.77)	0.61 (0.50, 0.82)	0.55 (0.47, 0.68)	0.69 (0.58, 0.77)	-0.09 (-0.23, 0.15)	0.13 (-0.07, 0.18)	–	0.22
Insulin dose (units/kg/day)							-0.03 (-0.13, 0.08)	0.61
lnIS†					-0.03(-0.15,0.03)	-0.06 (-0.18, 0.06)	–	0.64
CGM parameters
	16	13	16	14	13	14
MBG (mmol/L)							1.82 (-0.53, 4.17)	0.12
%CV							-1.91(-11.14, 7.32)	0.67
MAGE							1.67 (-1.12, 4.45)	0.23
MODD							0.49 (-0.66, 1.64)	0.38
Holter parameters
	15	14	15	14	14	14
SDNN (ms)							26.96 (2.24, 51.69)	0.03
SDANN (ms)							25.62 (0.15, 51.09)	0.049
RMSSD (ms)							17.90 (-3.08, 38.90)	0.09
PNN50							10.14 (3.74, 16.55)	0.004
LogLF (m^2)							0.08 (-0.15, 0.31)	0.46
LogHF (m^2)							0.38 (0.09, 0.66)	0.01
LF/HF							-0.47 (-0.75, -0.18)	0.006

Estimated treatment effect difference and value were derived from linear mixed effects models, with treatment stage, carryover, sequence, and treatment as fixed effects and study participant and sequence as nested random effects, unless otherwise noted. value was derived from the Wilcoxon signed rank test. † (mg/dL, to convert TG values from mmol/L to mg/dL, divide by 0.0113). BMI: body mass index; BP: blood pressure; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglyceride; CGM: continuous glucose monitoring; MBG: mean blood glucose; %CV: coefficient of variability of glycemia; MAGE: mean amplitude of glycemic excursions; MODD: means of daily differences; HRV: heart rate variability; SDNN: standard deviation of all RR intervals; SDANN: standard deviation of all the 5-minute RR intervals; RMSSD: square root of the mean of the sum of squares of differences between adjacent RR intervals; PNN50: the percentage of the interval differences of successive RR intervals greater than 50 ms; LF: low frequency; HF: high frequency; LF/HF: low frequency/high frequency.