INSPIRE Diabetes Study: Basal Bolus Insulin as Primary Treatment of Type 2 Diabetes

NCT ID: NCT01087567

Last Updated: 2014-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2014-01-31

Brief Summary

T2DM has become an American Epidemic. Currently 8% of the US population has diabetes and rates may be as high as 33% by the year 2050 (1). Although there are many treatment options for people with T2DM, none have been proven in humans to prevent the defects in insulin secretion (2) and insulin action (3) and beta cell dysfunction (4) that result with very high glucose levels and typically worsen as the disease progresses. Any treatment that could delay the progression of pancreatic beta cell failure (as measured by the need for rescue therapy with oral agents) would be a significant advancement in diabetes treatment.

Insulin therapy is appropriate at any point in T2DM disease progression, but it is commonly only used as a rescue therapy after failure of oral therapies. A number of outpatient insulin titration protocols have been shown to be safe and effective and speed patient's ability to gain glucose control (5-8). Recent studies have shown that initiation of insulin at onset of T2DM is beneficial at achieving early and long-term glucose control (6-9). However these protocols have used intravenous human insulin in the in-patient setting, continuous subcutaneous insulin by insulin pump or older human insulins in the out-patient setting. Many of these protocols are unlikely to be utilized in routine patient care. To date, no "insulin first" studies have been published with analog insulins in an outpatient basal-bolus regimen with patient driven titration.

Detailed Description

Insulin, when used as an initial treatment of T2DM, has a great potential to produce glucose control faster than any other treatment regimen. However, it is typically used as the treatment of last resort in T2DM. In this study, the investigators offer a novel approach to use insulin as the initial therapy in new-onset T2DM with the aim of determining its efficacy toward producing lasting glucose control.

Hypothesis: Treating newly diagnosed T2DM patients with insulin therapy versus standard of care for a short period of time will lead to improvement in glycemic control that is durable beyond the length of time taking the insulin and it may improve beta cell function.

Primary endpoints: Time to need rescue therapy, Need for rescue therapy at all time points. A1C change at 3, 6, 9 and 12 months.

Secondary endpoints: Mean glucose and mean fasting glucose at 3, 6, 12 months. C-peptide, HOMA-B, HOMA-IR, A1C the same time points, OGTT at week 12 and 56. Total number of hypoglycemic events (minor and major) and tolerability based on side effects.

Treatment arm: Weight based protocol of insulin Glargine and Glulisine. Control arm: oral medications per ADA 2009 recommended treatment algorithm. Rescue group available for both arms after initial 12 weeks.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intensive insulin regimen

A weight based, basal bolus will be given for 12 weeks.

Group Type: EXPERIMENTAL

Intensive insulin

Intervention Type: DRUG

A weight-based basal bolus insulin regimen starting with 0.1 units/kg/day of Glargine and 4 units/meal of Glulisine.

Routine Care

Routine Care patients receive oral medications based upon the 2009 ADA treatment recommendations: Metformin, Glimepiride, Pioglitazone.

Group Type: ACTIVE_COMPARATOR

Routine Care

Intervention Type: DRUG

Treatment in routine care will be based upon the 2009 ADA treatment recommendations.

Interventions

Intensive insulin

A weight-based basal bolus insulin regimen starting with 0.1 units/kg/day of Glargine and 4 units/meal of Glulisine.

Intervention Type: DRUG

Routine Care

Treatment in routine care will be based upon the 2009 ADA treatment recommendations.

Intervention Type: DRUG

Other Intervention Names

Lantus Insulin; Apidra Insulin; Metformin; Glimepiride; Pioglitazone

Eligibility Criteria

Inclusion Criteria

• Newly diagnosed T2DM (≤ 6 months since diagnosis)
• Drug naïve (less than 2 weeks of insulin and OHAs)
• A1C ≥ 8%
• Age ≥ 18 years
• Normal to high baseline C-peptide (≥ 0.5 ug/dL)
• FBG > 180 mg/dL, A1C > 8%.

Exclusion Criteria

• Pregnancy
• Clinically evident heart failure
• Nephrotic syndrome
• Allergy to insulin or any of the oral medications in the study
• Presence of anti-GAD antibodies
• Islet cell antibodies
• Anti-insulin antibodies
• Any physical disabilities that would preclude self-administration of injectable insulin.
• Evidence of hypoglycemia during screening phase.
• History of lactic acidosis, allergy to metformin or history of chronic renal disease or a serum creatinine > 1.5 in men or > 1.4 in women

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Western University of Health Sciences

OTHER

Sponsor Role: collaborator

Ohio University

OTHER

Sponsor Role: lead

Responsible Party

Jay Shubrook

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jay H Shubrook, D.O.

Role: PRINCIPAL_INVESTIGATOR

Ohio University

Locations

Ohio University

Athens, Ohio, United States

Countries

United States

References

Ryan EA, Imes S, Wallace C. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes. Diabetes Care. 2004 May;27(5):1028-32. doi: 10.2337/diacare.27.5.1028.

Reference Type: BACKGROUND

PMID: 15111515 (View on PubMed)

Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, Hu Y, Zhou Z, Yan X, Tian H, Ran X, Luo Z, Xian J, Yan L, Li F, Zeng L, Chen Y, Yang L, Yan S, Liu J, Li M, Fu Z, Cheng H. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet. 2008 May 24;371(9626):1753-60. doi: 10.1016/S0140-6736(08)60762-X.

Reference Type: BACKGROUND

PMID: 18502299 (View on PubMed)

Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. Diabetes Care. 2008 Oct;31(10):1927-32. doi: 10.2337/dc08-0075. Epub 2008 Jun 12.

Reference Type: BACKGROUND

PMID: 18556343 (View on PubMed)

Other Identifiers

16037

Identifier Type: -

Identifier Source: org_study_id