Trial Outcomes & Findings for A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL (NCT NCT01750567)

Last Updated: 2026-07-20

Results Overview

While patients are on metformin therapy, time to treatment failure will be defined as one or all of the following criteria: 1. ALC \> 5000 on 3 occasions after start of metformin treatment and increasing by 25% or more on each occasion, which will be measured every 3 months. 2. An increase of Rai Stage (0-3) by one stage. 3. An increase in any lymph node by \>50% as assessed by either physical exam (all patients) or CT scanning (only if ordered as part of routine clinical management). 4. Worsening cytopenias (Hemoglobin \<11 g/dl) associated with a bone marrow biopsy result indicating advanced stage CLL (packed CLL marrow).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

Until the patient meets failure criteria and stops Metformin; up to 6 months after start of metformin therapy and yearly thereafter, assessed up to 12 years

Results posted on

2026-07-20

Participant Flow

There were 4 screen fails

Participant milestones

Participant milestones
Measure	Metformin (Glucophage) The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Overall Study STARTED	37
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin (Glucophage) The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Overall Study Withdrawal by Subject	1
Overall Study Patient Discretion	4
Overall Study Non compliance	1
Overall Study Adverse Event	1

Baseline Characteristics

A Pilot Study of Metformin Therapy in Patients With Relapsed Chronic Lymphocytic Leukemia (CLL) and Untreated CLL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin (Glucophage) n=37 Participants The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Age, Categorical <=18 years	0 Participants n=20 Participants
Age, Categorical Between 18 and 65 years	22 Participants n=20 Participants
Age, Categorical >=65 years	15 Participants n=20 Participants
Sex: Female, Male Female	20 Participants n=20 Participants
Sex: Female, Male Male	17 Participants n=20 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=20 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	32 Participants n=20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=20 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=20 Participants
Race (NIH/OMB) Asian	0 Participants n=20 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=20 Participants
Race (NIH/OMB) Black or African American	0 Participants n=20 Participants
Race (NIH/OMB) White	35 Participants n=20 Participants
Race (NIH/OMB) More than one race	0 Participants n=20 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=20 Participants
Region of Enrollment United States	37 participants n=20 Participants

PRIMARY outcome

Timeframe: Until the patient meets failure criteria and stops Metformin; up to 6 months after start of metformin therapy and yearly thereafter, assessed up to 12 years

Outcome measures

Outcome measures
Measure	Metformin (Glucophage) n=35 Participants The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Time to Treatment Failure	0.80 years Interval 0.53 to upper limit was not reached

SECONDARY outcome

Timeframe: from time of diagnosis to time of first treatment with anti-neoplastic chemotherapy, assessed up to 12 years

Population: previously untreated patients with del(11q) mutation only

To evaluate TTFT in untreated patients, the product-limit method of Kaplan and Meier will be used similarly to the primary endpoint. The main difference between this endpoint and the primary endpoint is that TTFT will be defined from the date of CLL diagnosis for untreated delq11 patients

Outcome measures

Outcome measures
Measure	Metformin (Glucophage) n=17 Participants The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Time to First Therapy (TTFT) in Previously Untreated 11q CLL Subsets Only.	5.1 years Interval 3.5 to upper limit was not reached

SECONDARY outcome

Timeframe: Until the patient meets failure criteria and stops Metformin, assessed up to 12 years

Population: No data is available and data is unable to be collected as data was not electronically captured.

Longitudinal lymphocyte counts will be modeled using mixed models methodology, whereby both fixed effects (dose of metformin) and random effects (intercept - starting lymphocyte count) can be modeled.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 3 months after completing metformin therapy, assessed up to 12 years

Population: No data is available and data is unable to be collected as data was not electronically captured.

The proportion of patients that begin metformin therapy with these conditions will be summarized, along with the proportions at study defined clinical assessment points during therapy. No statistical models will be employed, but proportions and 95% exact binomial confidence intervals will be reported for descriptive purposes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline up to 3 months after completing metformin therapy, assessed up to 12 years

Population: percent of remaining patients from the 35 available, who did not have either lymphadenopathy or splenomegaly before starting metformin

The number of patients that begin metformin therapy with these conditions will be summarized, along with the proportions at study defined clinical assessment points during therapy. No statistical models will be employed, but proportions and 95% exact binomial confidence intervals will be reported for descriptive purposes.

Outcome measures

Outcome measures
Measure	Metformin (Glucophage) n=35 Participants The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy patients started with appreciated lymphadenopathy	16 Participants
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy of the remaining patients, how many developed lymphadenopathy on metformin	6 Participants
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy patients started with splenomegaly	1 Participants
Change in Number of Clinically Appreciated Lymphadenopathy and Splenomegaly While on Metformin Therapy of the remaining patients, how many developed splenomegaly on metformin	4 Participants

Adverse Events

Metformin (Glucophage)

Serious events: 3 serious events

Other events: 32 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Metformin (Glucophage) n=37 participants at risk The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
General disorders Abdominal pain	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Renal and urinary disorders Acute kidney injury	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Fever	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Renal and urinary disorders Hemolytic uremic syndrome	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Infections and infestations Lung infection	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Ear and labyrinth disorders Otitis externa	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.7% 1/37 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.

Other adverse events

Other adverse events
Measure	Metformin (Glucophage) n=37 participants at risk The starting dose of metformin was 500 mg po daily for one week. The dose was escalated to 500 mg twice a day after one week, and further escalated to the final dose of 1000 mg twice a day in week 3. Metformin: Metformin is an antidiabetic drug which is an inexpensive and generally well tolerated medication.
General disorders Chills	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders Constipation	13.5% 5/37 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders Diarrhea	45.9% 17/37 • Number of events 27 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Fatigue	37.8% 14/37 • Number of events 15 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Headache	13.5% 5/37 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Hot flashes	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Investigations Alanine aminotransferase increased	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders Bloating	5.4% 2/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders Nausea	21.6% 8/37 • Number of events 10 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders Stomach pain	8.1% 3/37 • Number of events 6 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Infections and infestations Urinary tract infection	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders abdominal cramping	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Investigations Alkaline phosphatase increased	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Investigations anemia	8.1% 3/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Musculoskeletal and connective tissue disorders Back Pain	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Respiratory, thoracic and mediastinal disorders Bronchitis	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders cough	10.8% 4/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Metabolism and nutrition disorders decreased appetite	13.5% 5/37 • Number of events 7 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders dizziness	16.2% 6/37 • Number of events 6 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Respiratory, thoracic and mediastinal disorders dyspnea	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Early Satiety	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders fever	16.2% 6/37 • Number of events 6 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders GI Discomfort	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Gastrointestinal disorders heartburn	5.4% 2/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Investigations Hyperbilirubinemia	5.4% 2/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Abdominal Cramps	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Metabolism and nutrition disorders Low appetite	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle Cramps	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Musculoskeletal and connective tissue disorders Muscle Pain	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders night sweats	10.8% 4/37 • Number of events 4 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders post nasal drip	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Productive Cough	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Skin and subcutaneous tissue disorders Rash (Poison Ivy)	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Infections and infestations Sinus infection	8.1% 3/37 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Sinusitis	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
General disorders Increased sweating	5.4% 2/37 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Investigations thrombocytopenia	5.4% 2/37 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Infections and infestations Upper Respiratory Infection	21.6% 8/37 • Number of events 8 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.
Metabolism and nutrition disorders weight loss	27.0% 10/37 • Number of events 10 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment, an average of 2.5 years per subject. Patients were monitored for 1 year after study removal or study treatment completion for all-cause mortality.

Additional Information

University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin

University of Michigan Rogel Cancer Center

Phone: 734-936-9499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place