Diabetes Mellitus, Type 2Phase 4NCT00191464

Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes

A Phase 4 study testing premeal insulin lispro mixtures, insulin glargine and metformin in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 7 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 35 to 75 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: premeal insulin lispro mixtures, insulin glargine and metformin
How many people: 320 participants
Where: 7 sitesin 7 countries
Study dates: Dec 2003to Sep 2005
Phase: Phase 4
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 35 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Have type 2 diabetes (World Health Organization [WHO] classification
Have used one or more of the following oral anti-hyperglycemic medications-metformin or second-generation sulfonylurea (for example, glibenclamide, glyburide, glipizide, gliclazide, glimepiride) alone or in combination with one or two insulin injections per day for at least 3 months immediately prior to entering the study. Patients using more than 2 insulin injections per day or subcutaneous insulin infusion prior to the study will not be eligible to participate.
Have a hemoglobin A1c between 6.5% and 11%, inclusive, according to the central laboratory at Visit 1.
Have clinically acceptable LDL-C, in the investigator's opinion, at Visit 1.
As determined by the investigator, are capable and willing to learn how to use the insulin injection pens; comply with their prescribed diet, exercise, and medication regimen; perform self-monitoring of blood glucose; and use the patient diary as required for this protocol.

Who cannot join

Have hypersensitivity to metformin or a known allergy to metformin hydrochloride, insulin lispro MM, insulin lispro LM, or insulin glargine, or excipients contained in these products.
Have known metabolic or lactic acidosis.
Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 135 micromol/L (1.5 mg/dL) for males and greater than or equal to 110 micromol/L (1.2 mg/dL) for females.
Have cardiac disease with functional status that is Class III or IV
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase (ALT) greater than three times the upper limit of the reference range as defined by the central laboratory.

Trial locations and contacts

7 sites in 7 countries.

Country

City, postcode or hospital

7 sites in 7 countries

United States1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Lebanon, New Hampshire, 03756

Other trials in United States

Australia1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
St Leonards, New South Wales, 2065

Other trials in Australia

Greece1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Thessaloniki, 56429

Other trials in Greece

India1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Mumbai, Maharstra, 400 007

Other trials in India

Netherlands1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Den Helder, 1783 GZ

Other trials in Netherlands

Poland1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Oleśnica, 56-400

Other trials in Poland

Puerto Rico1 site

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon-Fri from 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Ponce, 00731

Other trials in Puerto Rico

About this study

Official title: Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes: A Comparison of Premeal Insulin Lispro Mixtures to Once-Daily Insulin Glargine

The primary objective of this study is to show that a prandial insulin regimen, consisting of premeal insulin lispro "mid mixture" (or a combined regimen of insulin lispro "mid mixture" and insulin lispro "low mixture") plus metformin will result in significantly better overall glycemic control (lower HbA1c) at endpoint than once-daily insulin glargine plus metformin. Insulin lispro "mid mixture" consists of 50% insulin lispro and 50% NPL. Insulin lispro "low mixture" consists of 25% insulin lispro and 75% NPL.

In a substudy of approximately 60 patients, additional data will be collected on markers associated with risk of atherosclerosis or cardiovascular disease in the context of a controlled, outpatient, high-fat test meal.

Conditions: Diabetes Mellitus, Type 2
Being tested: premeal insulin lispro mixtures, insulin glargine, metformin
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

premeal insulin lispro mixturesDrug
insulin glargineDrug
metforminDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

HbA1C

Secondary outcomes (26)

General inflammation (hsCRP)
High-density lipoprotein cholesterol
Total cholesterol
Triglycerides
Estimates of low-density lipoprotein cholesterol
Nuclear magnetic resonance [NMR] analysis of lipids
Oxidized LDL
Lipoproteins and apoproteins
Fibrinogen
Blood glucose levels (based on self-monitoring)
Insulin dose
Weight
Frequency and incidence of hypoglycemia
Safety
General well-being
Pilot two questionnaires for microvascular complications
Coagulopathy factors [substudy]
Surrogate measure of vascular reactivity [substudy]
Inflammatory markers [substudy]
Production of advanced glycation end-products [substudy]
Generation of oxidative species [substudy]
Lipids in various fractions [substudy]
Retinyl ester measurements in various fractions [substudy]
Composition of triglyceride-rich lipoproteins [substudy]
Compartmental modeling of postprandial lipemia [substudy]
Apolipoproteins [substudy]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2003Sep 2005

First posted19 Sep 2005 (estimated)
Study startDec 2003
Study completionSep 2005

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (6)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 320 participants

IDs, dates and publications

ClinicalTrials.gov ID: NCT00191464
Sponsor's protocol ID: 6146
Other IDs: F3Z-MC-IOOI
Status last verified: Oct 2010
First submitted: 12 Sep 2005
Last updated: 13 Oct 2010
Results posted: No

Publications

Robbins DC, Beisswenger PJ, Ceriello A, Goldberg RB, Moses RG, Pagkalos EM, Milicevic Z, Jones CA, Sarwat S, Tan MH. Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2007 Nov;29(11):2349-64. doi: 10.1016/j.clinthera.2007.11.016.
PubMed 18158076
Hirsch IB, Yuan H, Campaigne BN, Tan MH. Impact of prandial plus basal vs basal insulin on glycemic variability in type 2 diabetic patients. Endocr Pract. 2009 May-Jun;15(4):343-8. doi: 10.4158/EP08308.ORR.
PubMed 19454394
Chan JY, Leyk M, Frier BM, Tan MH. Relationship between HbA1c and hypoglycaemia in patients with type 2 diabetes treated with different insulin regimens in combination with metformin. Diabetes Metab Res Rev. 2009 Mar;25(3):224-31. doi: 10.1002/dmrr.929.
PubMed 19156705
Shrom D, Sarwat S, Ilag L, Bloomgarden ZT. Does A1c consistently reflect mean plasma glucose? J Diabetes. 2010 Jun;2(2):92-6. doi: 10.1111/j.1753-0407.2010.00066.x. Epub 2010 Jan 22.
PubMed 20923490
Sarwat S, Ilag LL, Carey MA, Shrom DS, Heine RJ. The relationship between self-monitored blood glucose values and glycated haemoglobin in insulin-treated patients with Type 2 diabetes. Diabet Med. 2010 May;27(5):589-92. doi: 10.1111/j.1464-5491.2010.02955.x.
PubMed 20536957
Beisswenger PJ, Brown WV, Ceriello A, Le NA, Goldberg RB, Cooke JP, Robbins DC, Sarwat S, Yuan H, Jones CA, Tan MH; IOOI Study Investigators. Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor alpha are attenuated by prandial + basal insulin in patients with Type 2 diabetes. Diabet Med. 2011 Sep;28(9):1088-95. doi: 10.1111/j.1464-5491.2011.03324.x.
PubMed 21517955

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Diabetes Mellitus, Type 2 trials

Study at a glance

From the registry record, last updated by the sponsor on 13 Oct 2010. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes: A Comparison of Premeal Insulin Lispro Mixtures to Once-Daily Insulin Glargine
ClinicalTrials.gov ID: NCT00191464
Acronym / sponsor ID: 6146
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 320 participants
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Dec 2003
Study completion: Sep 2005
First posted: 19 Sep 2005 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)

Who may qualify

Ages: 35 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Have type 2 diabetes (World Health Organization [WHO] classification
Have used one or more of the following oral anti-hyperglycemic medications-metformin or second-generation sulfonylurea (for example, glibenclamide, glyburide, glipizide, gliclazide, glimepiride) alone or in combination with one or two insulin injections per day for at least 3 months immediately prior to entering the study. Patients using more than 2 insulin injections per day or subcutaneous insulin infusion prior to the study will not be eligible to participate.
Have a hemoglobin A1c between 6.5% and 11%, inclusive, according to the central laboratory at Visit 1.
Have clinically acceptable LDL-C, in the investigator's opinion, at Visit 1.
As determined by the investigator, are capable and willing to learn how to use the insulin injection pens; comply with their prescribed diet, exercise, and medication regimen; perform self-monitoring of blood glucose; and use the patient diary as required for this protocol.

Key exclusion criteria (5 listed)

Have hypersensitivity to metformin or a known allergy to metformin hydrochloride, insulin lispro MM, insulin lispro LM, or insulin glargine, or excipients contained in these products.
Have known metabolic or lactic acidosis.
Have a history of renal transplantation or are currently receiving renal dialysis or have serum creatinine greater than or equal to 135 micromol/L (1.5 mg/dL) for males and greater than or equal to 110 micromol/L (1.2 mg/dL) for females.
Have cardiac disease with functional status that is Class III or IV
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase (ALT) greater than three times the upper limit of the reference range as defined by the central laboratory.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
premeal insulin lispro mixtures	Drug	–
insulin glargine	Drug	–
metformin	Drug	–

Primary outcome

HbA1C

26 secondary outcomes

General inflammation (hsCRP)
High-density lipoprotein cholesterol
Total cholesterol
Triglycerides
Estimates of low-density lipoprotein cholesterol
Nuclear magnetic resonance [NMR] analysis of lipids
Oxidized LDL
Lipoproteins and apoproteins
Fibrinogen
Blood glucose levels (based on self-monitoring)
Insulin dose
Weight
Frequency and incidence of hypoglycemia
Safety
General well-being
Pilot two questionnaires for microvascular complications
Coagulopathy factors [substudy]
Surrogate measure of vascular reactivity [substudy]
Inflammatory markers [substudy]
Production of advanced glycation end-products [substudy]
Generation of oxidative species [substudy]
Lipids in various fractions [substudy]
Retinyl ester measurements in various fractions [substudy]
Composition of triglyceride-rich lipoproteins [substudy]
Compartmental modeling of postprandial lipemia [substudy]
Apolipoproteins [substudy]

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2010.
Background: PubMed 18158076Robbins DC, Beisswenger PJ, Ceriello A, Goldberg RB, Moses RG, Pagkalos EM, Milicevic Z, Jones CA, Sarwat S, Tan MH. Mealtime 50/50 basal + prandial insulin analogue mixture with a basal insulin analogue, both plus metformin, in the achievement of target HbA1c and pre- and postprandial blood glucose levels in patients with type 2 diabetes: a multinational, 24-week, randomized, open-label, parallel-group comparison. Clin Ther. 2007 Nov;29(11):2349-64. doi: 10.1016/j.clinthera.2007.11.016.
Results publication: PubMed 19454394Hirsch IB, Yuan H, Campaigne BN, Tan MH. Impact of prandial plus basal vs basal insulin on glycemic variability in type 2 diabetic patients. Endocr Pract. 2009 May-Jun;15(4):343-8. doi: 10.4158/EP08308.ORR.
Results publication: PubMed 19156705Chan JY, Leyk M, Frier BM, Tan MH. Relationship between HbA1c and hypoglycaemia in patients with type 2 diabetes treated with different insulin regimens in combination with metformin. Diabetes Metab Res Rev. 2009 Mar;25(3):224-31. doi: 10.1002/dmrr.929.
Results publication: PubMed 20923490Shrom D, Sarwat S, Ilag L, Bloomgarden ZT. Does A1c consistently reflect mean plasma glucose? J Diabetes. 2010 Jun;2(2):92-6. doi: 10.1111/j.1753-0407.2010.00066.x. Epub 2010 Jan 22.
Results publication: PubMed 20536957Sarwat S, Ilag LL, Carey MA, Shrom DS, Heine RJ. The relationship between self-monitored blood glucose values and glycated haemoglobin in insulin-treated patients with Type 2 diabetes. Diabet Med. 2010 May;27(5):589-92. doi: 10.1111/j.1464-5491.2010.02955.x.
Derived from this study: PubMed 21517955Beisswenger PJ, Brown WV, Ceriello A, Le NA, Goldberg RB, Cooke JP, Robbins DC, Sarwat S, Yuan H, Jones CA, Tan MH; IOOI Study Investigators. Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor alpha are attenuated by prandial + basal insulin in patients with Type 2 diabetes. Diabet Med. 2011 Sep;28(9):1088-95. doi: 10.1111/j.1464-5491.2011.03324.x.

Related trials for Diabetes Mellitus, Type 2

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

7 sites in 7 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing premeal insulin lispro mixtures, insulin glargine and metformin in people with Diabetes Mellitus, Type 2, run by Eli Lilly and Company at 7 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Oct 2010. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Australia, Greece, India, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HbA1C. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00191464, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2010.