Insulin sensitizer in prediabetes: a clinical study with DLBS3233, a combined bioactive fraction of Cinnamomum burmanii and Lagerstroemia speciosa

Figures & data

Table 1 Baseline and improvement of metabolic parameters by DLBS3233 in comparison with placebo

Parameter	DLBS3233 (n=38)		Placebo (n=36)		P-valueb
	Mean ± SD	P-valuea	Mean ± SD	P-valuea
Fasting plasma glucose (mmol/L) at baseline	5.43±0.48		5.56±0.48		NS
Change at Week 8	−0.12±1.89	NS	−0.02±0.54	NS	NS
Change at Week 12	−0.35±1.81	NS	−0.12±0.51	NS	NS
15-minute-postprandial glucose (mmol/L) at baseline	7.73±1.35		7.75±1.06		NS
Change at Week 8	−0.63±1.36	0.007	−0.14±1.04	NS	NS
Change at Week 12	−0.45±1.46	NS	−0.19±1.14	NS	NS
2-hour postprandial glucose (mmol/L) at baseline	8.90±0.82		9.16±0.88		NS
Change at Week 8	−0.94±1.57	0.001	−0.78±1.65	0.012	NS
Change at Week 12	−1.24±1.60	0.001	−1.06±1.92	0.006	NS
Fasting insulin (pmol/L) at baseline	84.38±41.7		76.16±56.41		NS
Change at Week 8	−23.39±31.81	<0.001	−19.49±53.78	0.005	NS
Change at Week 12	−23.25±35.86	<0.001	−14.8±53.59	NS	NS
15-minute-postprandial insulin (pmol/L) at baseline	435.27±223.19		378.08±167.22		NS
Change at Week 8	−133.80±198.96	<0.001	−95.42±204.91	0.012	0.018
Change at Week 12	−144.78±194.06	<0.001	−71.21±157.19	NS	0.022
2-hour postprandial insulin (pmol/L) at baseline	1,113.72±550.47		1,004.34±467.01		NS
Change at Week 8	−361.41±507.30	<0.001	−243.21±469.44	0.033	NS
Change at Week 12	−455.03±487.56	<0.001	−269.49±467.77	0.024	0.033
HOMA-IR at baseline	3.00±1.76		2.76±2.28		NS
Change at Week 8 (%)	−21.91±28.21	0.002	−13.63±33.62	0.005	NS
Change at Week 12 (%)	−27.04±29.41	0.001	−4.90±41.27	NS	0.013
Oral disposition index at baseline	0.51±0.30		0.64±0.53		NS
Change at Week 8	+0.25±0.81	0.012	−0.16±1.03	NS	0.032
Change at Week 12	+0.06±0.35	NS	−0.08±0.62	NS	NS
Estimated MCR (mL/kg/min) at baseline	2.97±2.97		3.27±2.73		NS
Change at Week 8	+2.38±2.79	<0.001	+1.82±3.19	<0.001	NS
Change at Week 12	+2.85±2.79	<0.001	+1.70±3.05	0.002	0.044
Fasting triglyceride at baseline (mmol/L)	1.49±0.70		1.39±0.63		NS
Change at Week 8	−0.30±0.63	0.008	−0.15±0.51	NS	NS
Change at Week 12	−0.32±0.62	0.004	−0.17±0.38	NS	NS

Notes:

a Within-group comparisons, statistical significance compared to baseline.

b Between-group comparisons. NS, not statistically significant (P>0.05). The changes in each parameter are the differences from their respective baseline levels. Negative values are reduction from baseline, while positive values, increase from baseline. Baseline: Week 0, before treatment.

Abbreviations: SD, standard deviation; HOMA-IR, homeostatic model assessment – insulin resistance; MCR, metabolic clearance rate.

Table 2 Effects on organ function and weight

Parameter	DLBS3233 (n=38)		Placebo (n=36)		P-valueb
	Mean ± SD	P-valuea	Mean ± SD	P-valuea
ALT (U/L) at baseline	29.8±16.8		30.2±18.0		NS
Change at Week 12	−7.0±11.7	0.001	−4.5±14.1	NS	NS
γ-GT (U/L) at baseline	26.8±26.5		28.0±14.6		NS
Change at Week 12	−4.8±14.7	NS	−3.3±14.0	NS	NS
AP (U/L) at baseline	69.2±18.8		72.50±19.36		NS
Change at Week 12	−6.3±12.8	0.001	−2.44±10.51	NS	NS
Creatinine (mmol/L) at baseline	55.692±11.492		67.184±21.216		0.026
Change at Week 12	3.536±10.608	NS	0.884±8.84	NS	NS
SBP (mmHg) at baseline	125.3±16.0		133.2±26.7		NS
Change at Week 12	−6.4±17.6	0.035	−4.3±27.9	NS	0.013
DBP (mmHg) at baseline	81.3±10.4		85.3±14.2		NS
Change at Week 12	−4.7±12.0	0.026	−3.3±15.3	NS	0.020
Weight (kg) at baseline	67.39±11.13		68.06±10.36		NS
Change at Week 12	−1.85±2.92	<0.001	−2.23±1.88	<0.001	NS

Notes:

a Within-group comparisons, statistical significance compared to baseline.

b Between-group comparisons. NS, not statistically significant (P>0.05). Negative values are reduction from baseline, while positive values, increase from baseline.

Abbreviations: SD, standard deviation; ALT, alanine transaminase; γ-GT, γ-glutamyl transferase; AP, alkaline phosphatase; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Figure 1 Improvement of insulin resistance and β-cell performance in each group.

Notes: (A) Percentage of HOMA-IR reduction from baseline. (B) First-phase insulin level (pmol/L) during OGTT. (C) Second-phase insulin secretion level (pmol/L) during OGTT. P-value resulted from statistical comparisons of delta from baseline, DLBS3233 vs placebo, individually at Week 8 and Week 12. *A significant difference (P<0.05) between groups was found. NS, not statistically significantly different (P>0.05). If a between-group comparison was not significant (P>0.05), the P-value was not mentioned, and only displayed as “NS”. Error bars represent standard error of means.
Abbreviations: HOMA-IR, homeostatic model assessment – insulin resistance; OGTT, oral glucose tolerance test.

Table 3 Adverse events

Adverse events	DLBS3233 (n=40)	Placebo (n=40)
	Number of events (number of subjects with event)
Central/peripheral nervous system
Anxiety	3 (2)	0
Appetite exaggerated	9 (7)	10 (7)
Dizziness	16 (10)	10 (7)
Drowsiness	0	1 (1)
Headache	8 (6)	2 (2)
Insomnia	1 (1)	1 (1)
Local coldness	1 (1)	0
Tremor	9 (5)	2 (2)
Vertigo	2 (1)	0
Cardiovascular system
Increased blood pressure	0	3 (3)
Palpitation	11 (6)	4 (4)
Ophthalmologic system
Blurred vision	1 (1)	0
Ear, nose, and throat system
Ear ache	1 (1)	0
Respiratory system
Coughing	0	1 (1)
Dyspnea	1 (1)	0
Laryngitis	1 (1)	0
Pharyngitis	0	1 (1)
Gastrointestinal system
Abdominal pain	0	2 (2)
Appendicitis	1 (1)	0
Constipation	1 (1)	1 (1)
Diarrhea	2 (2)	0
Gastritis	0	1 (1)
Nausea	2 (2)	1 (1)
Reproductive system
Menstrual disorder	3 (2)	0
Urinary system
Polyuria	0	2 (1)
Oliguria	0	1 (1)
Musculoskeletal system
Myalgia	4 (4)	4 (4)
Skin and appendages system
Acne	1 (1)	1 (1)
Dermatitis	0	2 (1)
Pruritus	2 (2)	2 (2)
Hyperpigmentation	0	1 (1)
Body as whole – general
Feeling unwell	1 (1)	0
Fever	1 (1)	3 (3)
General weakness	15 (9)	8 (6)
Influenza-like symptoms	1 (1)	0
Leg pain	2 (2)	1 (1)
Pain	1 (1)	0
Diaphoresis	7 (4)	5 (4)
Total	108 (20)	70 (19)

Note: One subject might have more than one adverse event.