Trial Outcomes & Findings for Vitamin D and Type 2 Diabetes Study (NCT NCT01942694)

Results Overview

New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

2423 participants

Primary outcome timeframe

Approximately 48 months

Results posted on

2022-08-16

Participant Flow

Participant milestones

Participant milestones
Measure	Placebo One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Overall Study STARTED	1212	1211
Overall Study COMPLETED	1211	1211
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vitamin D and Type 2 Diabetes Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.	Total n=2423 Participants Total of all reporting groups
Age, Continuous	60.4 years STANDARD_DEVIATION 10.0 • n=5 Participants	59.6 years STANDARD_DEVIATION 9.9 • n=7 Participants	60.0 years STANDARD_DEVIATION 9.9 • n=5 Participants
Sex: Female, Male Female	545 Participants n=5 Participants	541 Participants n=7 Participants	1086 Participants n=5 Participants
Sex: Female, Male Male	667 Participants n=5 Participants	670 Participants n=7 Participants	1337 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	105 Participants n=5 Participants	120 Participants n=7 Participants	225 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1107 Participants n=5 Participants	1091 Participants n=7 Participants	2198 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Asian	64 Participants n=5 Participants	66 Participants n=7 Participants	130 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Black or African American	315 Participants n=5 Participants	301 Participants n=7 Participants	616 Participants n=5 Participants
Race (NIH/OMB) White	806 Participants n=5 Participants	810 Participants n=7 Participants	1616 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	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants
Region of Enrollment United States	1212 participants n=5 Participants	1211 participants n=7 Participants	2423 participants n=5 Participants
Fasting plasma glucose (mg/dl)	107.8 mg/dl STANDARD_DEVIATION 7.4 • n=5 Participants	108.0 mg/dl STANDARD_DEVIATION 7.4 • n=7 Participants	107.9 mg/dl STANDARD_DEVIATION 7.4 • n=5 Participants
2-Hr post-load plasma glucose (mg/dl)	137.6 mg/dl STANDARD_DEVIATION 34.3 • n=5 Participants	136.9 mg/dl STANDARD_DEVIATION 34.3 • n=7 Participants	137.2 mg/dl STANDARD_DEVIATION 34.3 • n=5 Participants
Glycated hemoglobin (%)	5.9 % STANDARD_DEVIATION 0.2 • n=5 Participants	5.9 % STANDARD_DEVIATION 0.2 • n=7 Participants	5.9 % STANDARD_DEVIATION 0.2 • n=5 Participants
Serum 25-hydroxyvitamin D (ng/ml)	28.2 ng/ml STANDARD_DEVIATION 10.1 • n=5 Participants	27.7 ng/ml STANDARD_DEVIATION 10.2 • n=7 Participants	28.0 ng/ml STANDARD_DEVIATION 10.2 • n=5 Participants

PRIMARY outcome

Timeframe: Approximately 48 months

New-onset diabetes was based on annual glycemic testing of fasting plasma glucose, glycated hemoglobin, and 2-hour post-load plasma glucose and semiannual testing of fasting plasma glucose and glycated hemoglobin. If two or three of the glycemic measures met the 2010 ADA thresholds for diabetes, the participant was considered to have met the diabetes outcome. When only the measure for fasting plasma glucose or glycated hemoglobin met the threshold, confirmatory testing was performed for the positive measure within 8 weeks. If only the measure for 2-hour post-load plasma glucose met the threshold, then a 75-g oral glucose tolerance test to reassess all three glycemic measures was repeated. If the repeat measure was positive or both fasting plasma glucose and glycated hemoglobin were positive (in the case of a repeat oral glucose tolerance test), than the participant was considered to have met the diabetes outcome.

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Time to Development of Diabetes	323 Participants	293 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 48 months

Race and ethnic group were reporting by the participant. The category "other" includes American Indian or Alaska Native; Native Hawaiian or other Pacific Islander; and other race. Ethnic group includes any race.

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) Race: White	806 Participants	810 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) Race: Black	315 Participants	301 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) Race: Other	91 Participants	100 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) Ethnic Group: Hispanic	105 Participants	120 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Race (as a Proxy for Skin Pigmentation) Ethnic Group: Non-Hispanic	1107 Participants	1091 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Participants met at least two of three glycemic criteria for prediabetes: fasting plasma glucose level, 100 to 125 mg per deciliter (5.6 to 6.9 mmol per liter); plasma glucose level 2 hours after a 75-g oral glucose load, 140 to 199 mg per deciliter (7.8 to 11.0 mmol per liter) (impaired glucose tolerance); and glycated hemoglobin level, 5.7 to 6.4% (39 to 47 mmol per mole).

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) Met all three criteria	429 Participants	427 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Pre-diabetes Criteria (Two vs. Three Criteria) Met two criteria	783 Participants	784 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI <30	429 Participants	435 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: BMI ≥30	783 Participants	776 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference <Median of 104.2 cm	585 Participants	620 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Waist Circumference ≥Median of 104.2 cm	627 Participants	591 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age 25-44	103 Participants	106 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age 45-59	439 Participants	468 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Age ≥ 60	670 Participants	637 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) At or above 37° north latitude	898 Participants	892 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Geographic Location (as a Proxy for Sun Exposure) Below 37° north latitude	314 Participants	319 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome measures
Measure	Placebo n=1212 Participants One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 Participants One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements No intake	793 Participants	826 Participants
Variability of Response to Vitamin D Supplementation by Baseline Characteristic: Calcium Intake From Supplements Any intake	419 Participants	385 Participants

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 months for approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 months for approximately 48 months.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 months for approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 months for approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 months for approximately 48 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 12 months for approximately 48 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Approximately 48 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: One time assessment at the month 24 visit.

Outcome measures

Outcome data not reported

Adverse Events

Placebo

Serious events: 153 serious events

Other events: 26 other events

Deaths: 5 deaths

Vitamin D (Cholecalciferol)

Serious events: 173 serious events

Other events: 31 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=1212 participants at risk One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 participants at risk One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Cardiac disorders Death	0.41% 5/1212 • 2.5 years	0.41% 5/1211 • 2.5 years
Cardiac disorders Hospitalization	12.2% 148/1212 • 2.5 years	13.9% 168/1211 • 2.5 years

Other adverse events

Other adverse events
Measure	Placebo n=1212 participants at risk One pill daily Placebo: Administered as one soft-gel pill daily by mouth	Vitamin D (Cholecalciferol) n=1211 participants at risk One vitamin D pill daily Vitamin D (Cholecalciferol): Vitamin D (Cholecalciferol) 4000 IU, administered as 1 soft-gel pill daily by mouth.
Endocrine disorders Hypercalcemia	0.25% 3/1212 • Number of events 3 • 2.5 years	0.41% 5/1211 • Number of events 5 • 2.5 years
Endocrine disorders Fasting urine calcium: creatinine ratio >0.375	0.08% 1/1212 • Number of events 1 • 2.5 years	0.08% 1/1211 • Number of events 1 • 2.5 years
Endocrine disorders Low estimated glomerular filtration rate	0.17% 2/1212 • Number of events 2 • 2.5 years	0.08% 1/1211 • Number of events 1 • 2.5 years
Endocrine disorders Nephrolithiasis	1.7% 20/1212 • Number of events 21 • 2.5 years	2.0% 24/1211 • Number of events 25 • 2.5 years

Additional Information

Dr. Anastassios Pittas

Division of Endocrinology, Diabetes, and Metabolism, Tufts Medical Center

Phone: 617-636-3232

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place