Trial Outcomes & Findings for Beta-Cell Dysfunction and Insulin Resistance Among Italian Patients With Type 2 Diabetes (MK-0000-113) (NCT NCT01472341)

Results Overview

HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5.

Recruitment status

COMPLETED

Target enrollment

507 participants

Primary outcome timeframe

Baseline and 4 years

Results posted on

2017-03-10

Participant Flow

This observational study was conducted at 9 outpatient diabetes clinics in Italy.

Participant milestones

Participant milestones
Measure	All Participants Participants receiving routine care under a diabetologist.
Overall Study STARTED	507
Overall Study COMPLETED	235
Overall Study NOT COMPLETED	272

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Participants receiving routine care under a diabetologist.
Overall Study Started insulin therapy	55
Overall Study Started therapy with a DPP-IV/GLP-1	92
Overall Study Withdrawal by Subject	39
Overall Study Lost to Follow-up	52
Overall Study Laboratory parameters unavailable	25
Overall Study Death	9

Baseline Characteristics

Beta-Cell Dysfunction and Insulin Resistance Among Italian Patients With Type 2 Diabetes (MK-0000-113)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=507 Participants Participants receiving routine care under a diabetologist.
Age, Continuous	62.8 years STANDARD_DEVIATION 8.1 • n=5 Participants
Sex: Female, Male Female	209 Participants n=5 Participants
Sex: Female, Male Male	298 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 4 years

Population: Participants who had laboratory parameters at Baseline and at Year 4.

HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5.

Outcome measures

Outcome measures
Measure	All Participants n=235 Participants Participants receiving routine care under a diabetologist.
Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years HOMA-B at Baseline	50.2 Percentage of Beta Cell Function Standard Deviation 49.1
Change From Baseline in Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) at 4 Years HOMA-B at Year 4	48.3 Percentage of Beta Cell Function Standard Deviation 36.3

PRIMARY outcome

Timeframe: Baseline and Year 4

Population: Participants who had laboratory parameters at Baseline and at Year 4.

Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. A raised proinsulin-to-insulin ratio due to impaired processing of proinsulin is an early marker of beta cell dysfunction. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.

Outcome measures

Outcome measures
Measure	All Participants n=235 Participants Participants receiving routine care under a diabetologist.
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years PI/I at Baseline	1.19 PI/I Standard Deviation 1.86
Change From Baseline in Proinsulin/Insulin (PI/I) Ratio at 4 Years PI/I at Year 4	1.61 PI/I Standard Deviation 1.72

PRIMARY outcome

Timeframe: Baseline

Population: Participants with fasting plasma insulin and glucose concentration assessments at baseline.

HOMA is a method used to quantify insulin resistance (a condition in which natural hormone insulin becomes less effective in lowering blood sugars) and beta-cell (specialized cells in the pancreas producing insulin) function. HOMA uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. HOMA%B was defined as 20 x fasting insulin (mU/L)/fasting glucose (mmol/L) - 3.5. Beta-cell dysfunction was evaluated by calculating the PI/I ratio, which estimates the capacity of beta cells to convert proinsulin to insulin and may represent an acceptable method to indicate the degree of beta-cell secretion.

Outcome measures

Outcome measures
Measure	All Participants n=504 Participants Participants receiving routine care under a diabetologist.
Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio I. PI/PII <=0.485	73.4 Percentage Beta Cell Function Standard Deviation 63.8
Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio II. PI/PII 0.485 to 0.80	51.6 Percentage Beta Cell Function Standard Deviation 33.2
Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio III. PI/PII 0.81 to 1.355	37.7 Percentage Beta Cell Function Standard Deviation 30.4
Homeostatic Model Assessment Fasting Beta Cell Function (HOMA % B) According to Quartiles of Proinsulin/Insulin (PI/I) Ratio IV PI/PII >1.355	29.9 Percentage Beta Cell Function Standard Deviation 33.4

Adverse Events

All Participants

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=507 participants at risk Participants receiving routine care under a diabetologist.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death due to parotid cancer in advanced stage [Salivary gland cancer]	0.20% 1/507 • Number of events 1 There were no plans for the systematic collection or analysis of serious adverse events (SAEs) or adverse events (AEs) in the MK-0000-113 trial. Any SAEs or AEs reported were unsolicited and non-systematically assessed.

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Each site can publish its own results without the results of other sites after the publication of the study or after 24 months from completion of publication. The author list will be established with the participating sites before the layout of the text to be published. The company will need to evaluate all the proposed summaries, manuscripts or presentations 60 days prior to publication. The revision made by Company could be accelerated in order to satisfy the guidelines concerning publication.
Publication restrictions are in place

Restriction type: OTHER