Trial Outcomes & Findings for Adjunctive Metformin Therapy in Double Diabetes (NCT NCT01334125)

Results Overview

Comparison of the baseline-adjusted differences in HbA1c between the metformin and placebo groups during the trial. Hemoglobin A1c is a marker of glycemic control. The reported values represented means adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

28 participants

Primary outcome timeframe

Baseline, 3mo, 6mo, and 9 months

Results posted on

2016-03-04

Participant Flow

This study was conducted at a tertiary institution. The first patient was recruited on March 3rd 2011, and the last study patient was recruited on August 1, 2013. The study was closed on August 8, 2013.

Following enrollment, all subjects entered a run-in phase of 3-month duration during which participants were placed on insulin aspart and insulin detemir, and the treat-to-target insulin regimen (TTIR) started.

Participant milestones

Participant milestones
Measure	Metformin Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo 1 capsule once daily by mouth for 9 months Placebo: 1 capsule once daily by mouth for 9 months
Overall Study STARTED	15	13
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo 1 capsule once daily by mouth for 9 months Placebo: 1 capsule once daily by mouth for 9 months
Overall Study Lost to Follow-up	3	3

Baseline Characteristics

Adjunctive Metformin Therapy in Double Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin n=15 Participants Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 Participants 1 capsule once daily by mouth for 9 months Placebo: 1 capsules once daily by mouth for 9 months	Total n=28 Participants Total of all reporting groups
Age, Continuous	15 years STANDARD_DEVIATION 2.5 • n=93 Participants	14.5 years STANDARD_DEVIATION 3.1 • n=4 Participants	14.7 years STANDARD_DEVIATION 2.7 • n=27 Participants
Sex: Female, Male Female	7 Participants n=93 Participants	8 Participants n=4 Participants	15 Participants n=27 Participants
Sex: Female, Male Male	8 Participants n=93 Participants	5 Participants n=4 Participants	13 Participants n=27 Participants
Region of Enrollment United States	15 participants n=93 Participants	13 participants n=4 Participants	28 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 3mo, 6mo, and 9 months

Comparison of the baseline-adjusted differences in HbA1c between the metformin and placebo groups during the trial. Hemoglobin A1c is a marker of glycemic control. The reported values represented means adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

Outcome measures

Outcome measures
Measure	Metformin n=15 Participants Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 Participants 1 capsule once daily by mouth for 9 months Placebo: 1 capsules once daily by mouth for 9 months
Baseline Adjusted Hemoglobin A1c Over Time	9.46 percentage of HbA1c Interval 8.47 to 10.46	9.85 percentage of HbA1c Interval 8.82 to 10.88

SECONDARY outcome

Timeframe: Baseline, 3mo, 6mo, and 9 months

Comparison of the baseline-adjusted differences in total cholesterol/high density cholesterol index over time between the metformin and the placebo groups. The reported values represented means adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

Outcome measures

Outcome measures
Measure	Metformin n=15 Participants Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 Participants 1 capsule once daily by mouth for 9 months Placebo: 1 capsules once daily by mouth for 9 months
Baseline Adjusted Changes in Lipid Profile Over Time	3.5 ratio Interval 3.0 to 4.1	4 ratio Interval 3.3 to 4.4

SECONDARY outcome

Timeframe: Baseline, 3mo, 6 mo, and 9 months

Comparison of the baseline-adjusted differences in adiponectin/leptin ratio over time between the metformin and the placebo groups. The reported values represented mean adjusted for baseline values, age, gender, and BMI using repeated measures ANOVA (General Linear Model).

Outcome measures

Outcome measures
Measure	Metformin n=15 Participants Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 Participants 1 capsule once daily by mouth for 9 months Placebo: 1 capsules once daily by mouth for 9 months
Baseline Adjusted Changes in Adiponectin/Leptin Ratio Over Time	2.0 ratio Interval 0.84 to 3.2	1.2 ratio Interval 0.11 to 2.3

SECONDARY outcome

Timeframe: 12 months

Comparison of the occurrence of hypoglycemic event requiring a third party assistance (major hypoglycemia) per subject during the study, and minor hypoglycemia (plasma glucose of \<60 mg/dL or no measurement), as well as nocturnal hypoglycemia (plasma glucose of ≤60 mg/dL between 11PM and 6AM).

Outcome measures

Outcome measures
Measure	Metformin n=15 Participants Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 Participants 1 capsule once daily by mouth for 9 months Placebo: 1 capsules once daily by mouth for 9 months
Number of Participants With Minor, Major, and Nocturnal Hypoglycemia Minor hypoglycemia	3 participants	2 participants
Number of Participants With Minor, Major, and Nocturnal Hypoglycemia Major hypoglycemia	1 participants	0 participants
Number of Participants With Minor, Major, and Nocturnal Hypoglycemia Nocturnal hypoglycemia	2 participants	2 participants

Adverse Events

Metformin

Serious events: 4 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Metformin n=15 participants at risk Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 participants at risk 1 capsule once daily by mouth for 9 months Placebo: 1 capsule once daily by mouth for 9 months
Gastrointestinal disorders Appendicitis	6.7% 1/15 • Number of events 1 • 12 months	0.00% 0/13 • 12 months
Endocrine disorders Diabetic ketoacidosis	13.3% 2/15 • Number of events 2 • 12 months	0.00% 0/13 • 12 months
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/15 • 12 months	7.7% 1/13 • Number of events 1 • 12 months
Endocrine disorders Severe hypoglycemia	6.7% 1/15 • Number of events 1 • 12 months	0.00% 0/13 • 12 months

Other adverse events

Other adverse events
Measure	Metformin n=15 participants at risk Metformin 1000 mg once daily by mouth for 9 months Metformin: Metformin 1000 mg once daily by mouth for 9 months	Placebo n=13 participants at risk 1 capsule once daily by mouth for 9 months Placebo: 1 capsule once daily by mouth for 9 months
Eye disorders Eye infection	6.7% 1/15 • Number of events 1 • 12 months	0.00% 0/13 • 12 months
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	0.00% 0/15 • 12 months	7.7% 1/13 • Number of events 1 • 12 months
Ear and labyrinth disorders Otitis media	0.00% 0/15 • 12 months	7.7% 1/13 • Number of events 1 • 12 months
Immune system disorders Hidradenitis	0.00% 0/15 • 12 months	7.7% 1/13 • Number of events 1 • 12 months

Additional Information

Benjamin U. Nwosu, MD

University of Massachusetts Medical School

Phone: 5083347872

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place