Trial Outcomes & Findings for Metformin in Kidney Disease (NCT NCT02252081)

NCT ID: NCT02252081

Last Updated: 2021-11-04

Results Overview

Change in leptin to adiponectin ratio (LAR) after 4 months of metformin vs. placebo will be assessed as a biomarker of insulin resistance in CKD

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 125 participants
• Primary outcome timeframe: 16 weeks after start of treatment
• Results posted on: 2021-11-04

Participant Flow

65 patients did not meet inclusion criteria (normal GFR or to low GFR, new diabetes diagnosis, uncontrolled hypertension) or decline to participate.

Participant milestones

Measure	Metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min metformin: 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min	Placebo placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Overall Study STARTED	30	30
Overall Study COMPLETED	24	26
Overall Study NOT COMPLETED	6	4

Reasons for withdrawal

Measure	Metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min metformin: 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min	Placebo placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Overall Study Withdrawal by Subject	2	1
Overall Study Adverse Event	4	1
Overall Study non compliance & others	0	2

Baseline Characteristics

Metformin in Kidney Disease

Baseline characteristics by cohort

Measure	Metformin n=30 Participants 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min metformin: 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min	Placebo n=30 Participants placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks	Total n=60 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	66 years n=7 Participants	67 years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 16 weeks after start of treatment

Population: analyzed as log transformed using ANCOVA of change, ng/µg (log transformed value)

Change in leptin to adiponectin ratio (LAR) after 4 months of metformin vs. placebo will be assessed as a biomarker of insulin resistance in CKD

Outcome measures

Measure	Metformin n=24 Participants metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min/1.73m\^2; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min/1.73m\^2 Placebo: placebo pill(s) orally per day for 16 weeks	Placebo n=26 Participants placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Change is Leptin to Adiponectin Ratio (LAR) baseline	2.2 ng/micrograms Interval 1.5 to 3.2	1.3 ng/micrograms Interval 0.6 to 3.6
Change is Leptin to Adiponectin Ratio (LAR) Week 16	1.3 ng/micrograms Interval 1.0 to 2.6	1.4 ng/micrograms Interval 0.5 to 3.5

SECONDARY outcome

Timeframe: 16 weeks after the start of treatment

Change in FMD after 4 months of treatment with metformin will be compared to change in the placebo group.

Outcome measures

Measure	Metformin n=24 Participants metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min/1.73m\^2; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min/1.73m\^2 Placebo: placebo pill(s) orally per day for 16 weeks	Placebo n=26 Participants placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Change in Flow-mediated Dilation (FMD) baseline	5.1 change in percent Interval 3.2 to 8.4	5.0 change in percent Interval 3.7 to 8.7
Change in Flow-mediated Dilation (FMD) week 16	9.5 change in percent Interval 5.4 to 18.8	6.2 change in percent Interval 4.2 to 11.0

SECONDARY outcome

Timeframe: 16 weeks after starting treatment

is a measurement of stiffening of the large elastic arteries and atherosclerosis. It is a subclinical marker of cardiovascular disease

Outcome measures

Measure	Metformin n=24 Participants metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min/1.73m\^2; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min/1.73m\^2 Placebo: placebo pill(s) orally per day for 16 weeks	Placebo n=26 Participants placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Aortic Pulse-wave Velocity (aPWV) baseline aPWV (cm/s)	9.6 cm/s Interval 8.2 to 11.4	9.8 cm/s Interval 8.4 to 12.2
Aortic Pulse-wave Velocity (aPWV) Week16 aPWC (cm/s)	9.9 cm/s Interval 8.9 to 10.9	9.9 cm/s Interval 8.6 to 11.0

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 16 weeks after starting treatment

Population: kidney function measurement

eGFR is a measurement of kidney function, this was a descriptive measurement

Outcome measures

Measure	Metformin n=24 Participants metformin 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min/1.73m\^2; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min/1.73m\^2 Placebo: placebo pill(s) orally per day for 16 weeks	Placebo n=26 Participants placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Estimated Glomerular Filtration Rate (eGFR) baseline GFR	49.5 ml/min Interval 46.5 to 54.2	48.5 ml/min Interval 45.4 to 56.6
Estimated Glomerular Filtration Rate (eGFR) Week 16 GFR	52 ml/min Interval 45.25 to 54.9	48.7 ml/min Interval 43.9 to 56.5

Adverse Events

Metformin

Serious events: 2 serious events

Other events: 16 other events

Deaths: 18 deaths

Placebo

Serious events: 2 serious events

Other events: 6 other events

Deaths: 8 deaths

Serious adverse events

Measure	Metformin n=30 participants at risk 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min metformin: 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min	Placebo n=30 participants at risk placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Cardiac disorders acute coronary syndrome	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions	0.00% 0/30 • 16 weeks clinicaltrials.gov definitions
Respiratory, thoracic and mediastinal disorders pneumonia & pneumonia related complications	0.00% 0/30 • 16 weeks clinicaltrials.gov definitions	6.7% 2/30 • Number of events 2 • 16 weeks clinicaltrials.gov definitions
Cardiac disorders Pericarditis & chest pain	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions	0.00% 0/30 • 16 weeks clinicaltrials.gov definitions

Other adverse events

Measure	Metformin n=30 participants at risk 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min metformin: 500 to 1500 mg orally per day for 16 weeks if eGFR \> 45 ml/min; 500 to 1000 mg orally per day for 16 weeks if eGFR =\< 45 ml/min	Placebo n=30 participants at risk placebo pill(s) orally per day for 16 weeks Placebo: placebo pill(s) orally per day for 16 weeks
Gastrointestinal disorders diarrhea/loose stools/flatulence	26.7% 8/30 • Number of events 8 • 16 weeks clinicaltrials.gov definitions	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions
General disorders Generalized fatigue	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions
Blood and lymphatic system disorders Hyperlactetemia without acidosis >3.5 mmol/L	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions
Respiratory, thoracic and mediastinal disorders Asthma	10.0% 3/30 • Number of events 3 • 16 weeks clinicaltrials.gov definitions	0.00% 0/30 • 16 weeks clinicaltrials.gov definitions
Infections and infestations Upper respiratory infection	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions	6.7% 2/30 • Number of events 2 • 16 weeks clinicaltrials.gov definitions
Gastrointestinal disorders left lower quadrant pain	6.7% 2/30 • Number of events 2 • 16 weeks clinicaltrials.gov definitions	3.3% 1/30 • Number of events 1 • 16 weeks clinicaltrials.gov definitions

Additional Information

Dr. Adriana Hung

Nashville Campus TVHS

Phone: 6153274751

Email: adriana.hung@va.goc

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place