Study on Liver Fat Content and Visceral Fat Mass in Overweight and Obese Type 2 Diabetes Patients After Treatment With Basal Insulin

NCT01310452 | Unknown

• 1 other identifier: prof gao xin
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: To compare the change in liver fat content and visceral fat mass (cm2) assessed by MRS (Magnetic Resonance Spectroscopy) and MRI (Magnetic Resonance Image), after 26 weeks of treatment with insulin detemir once daily or insulin NPH once daily both with metformin in overweight and obese type 2 diabetic subjects. Secondary objectives: To compare the two treatments with respect to:

• MRI: abdominal subcutaneous fat mass(cm2), Calculated Visceral/Subcutaneous Adipose Tissue Ratio.
• Change in HbA1c from baseline at 12 and 26 weeks of treatment.
• Change in Fasting plasma glucose from baseline at 12 and 26 weeks of treatment.
• Weight
• Waist and hip circumference
• Safety:
• Incidence of hypoglycaemia in the 26 weeks of treatment with insulin detemir versus NPH
• Lipid profile at the start and after 26 weeks of treatment
• Incidence of Adverse events during the trial
• Safety profile as measured by laboratory safety parameters (haematology, biochemistry) and physical examination/vital signs before and at the end of treatment

Conditions

Type 2 Diabetes Mellitus

Keywords

diabetes, basal insulin, metformin, liver fat, visceral fat

Outcome Measures

Primary Outcomes (1)

• The change in liver fat content and visceral fat mass

  To compare the change in liver fat content and visceral fat mass (cm2), assessed by MRS and MRI, after 26 weeks of treatment with insulin detemir or insulin NPH (both with metformin) in overweight and obese type 2 diabetic subjects

  After 26 weeks of treatment

Secondary Outcomes (9)

• MRI

  after 26 weeks of treatment

• Change in HbA1c

  from baseline to 12 and 26 weeks of treatment respectively

• Change in Fasting plasma glucose

  From baseline to 12 and 26 weeks

• Weight at every visit

  At every visit

• Waist and hip circumference at every visit

  At every visit

Study Arms (2)

neutral protamine insulin, metformin

ACTIVE COMPARATOR

NPH insulin once daily plus oral metformin twice or thrice daily during 26 weeks

Drug: insulin detemir

insulin detemir, metformin

EXPERIMENTAL

Insulin detemir once daily plus oral metformin twice or thrice daily during 26 weeks

Drug: neutral protamine insulin

Interventions

insulin detemir DRUG

insulin detemir once daily with metformin

neutral protamine insulin, metformin

neutral protamine insulin DRUG

neutral protamine insulin once daily with metformin

insulin detemir, metformin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent obtained before any trial-related activities. (Trial-related activities are any procedure that would not have been performed during normal management of the subject.)
• Female or male, 18 years≤age≤70years
• Subjects with insulin naïve type 2 diabetes who have been treated with metformin（\>1g/d）alone for at least 3 months prior to screening
• %≥HbA1c≥7.5% based on analysis from a central laboratory
• kg/m2≤BMI≤40kg/m2
• Weight fluctuation\<2kg in one month prior to screening
• Able and willing to perform self-monitoring of blood glucose.
• Willing to accept basal insulin therapy
• Able to self-inject all required doses of insulin

You may not qualify if:

• Treatment with any OADs (Oral Antidiabetic Drugs) in the last 6 months, except metformin (subjects currently treated with metformin within the interval of 1000-2000 mg daily may be included in the trial. The dose should have remained unchanged for a period of one month prior to randomisation and should be expected to remain unchanged throughout the trial period).
• Use of approved weight lowering pharmacotherapy (e.g. orlistat, sibutramine, rimonabant) or obesity induced by drug treatment (e.g. corticosteroids, NSAIDs, tricyclic anti-depressants, atypical anti-psychotics).
• Participation in a clinical study of weight control within the last 3 months prior to screening.
• Previous or planned surgical treatment of obesity.
• Any disease or condition (such as renal, hepatic or cardiac) according to the judgment of the Investigator makes the subject unsuitable for participation in the trial.
• Anticipated change in concomitant medication known to interfere with glucose metabolism, such as systemic steroids, non-selective beta-blockers or mono amine oxidase (MAO) inhibitors.
• Anticipated change in concomitant medication known to interfere with lipid metabolism, such as lipid-lowering drugs.
• Proliferative retinopathy or maculopathy that has required acute treatment within the last six months.
• Uncontrolled hypertension (treated or untreated) as judged by the Investigator
• Known or suspected allergy to trial product(s) or related products.
• Previous participation in this trial. Participation is defined as screened.
• Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures. Adequate contraceptive measures are sterilisation, intrauterine device (IUD), oral contraceptives or consistent use of barrier methods.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
• Any condition that the Investigator feels would interfere with trial participation or evaluation of results.
• Receipt of any investigational drug (NPH or insulin detemir) within 1 month prior to this trial.

Sponsors & Collaborators

• Fudan University: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

Zhong Shan Hospital, Fudan University

Shanghai, China

Location

Related Publications (10)

• Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22.

  PMID: 18945920 BACKGROUND

• Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998 Sep 12;352(9131):837-53.

  PMID: 9742976 BACKGROUND

• Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008 Oct 9;359(15):1577-89. doi: 10.1056/NEJMoa0806470. Epub 2008 Sep 10.

  PMID: 18784090 BACKGROUND

• Mokdad AH, Ford ES, Bowman BA, Nelson DE, Engelgau MM, Vinicor F, Marks JS. Diabetes trends in the U.S.: 1990-1998. Diabetes Care. 2000 Sep;23(9):1278-83. doi: 10.2337/diacare.23.9.1278.

  PMID: 10977060 BACKGROUND

• Lean ME, Powrie JK, Anderson AS, Garthwaite PH. Obesity, weight loss and prognosis in type 2 diabetes. Diabet Med. 1990 Mar-Apr;7(3):228-33. doi: 10.1111/j.1464-5491.1990.tb01375.x.

  PMID: 2139394 BACKGROUND

• Hollander P, Raslova K, Skjoth TV, Rastam J, Liutkus JF. Efficacy and safety of insulin detemir once daily in combination with sitagliptin and metformin: the TRANSITION randomized controlled trial. Diabetes Obes Metab. 2011 Mar;13(3):268-75. doi: 10.1111/j.1463-1326.2010.01351.x.

  PMID: 21205123 BACKGROUND

• Whittingham JL, Havelund S, Jonassen I. Crystal structure of a prolonged-acting insulin with albumin-binding properties. Biochemistry. 1997 Mar 11;36(10):2826-31. doi: 10.1021/bi9625105.

  PMID: 9062110 BACKGROUND

• Philis-Tsimikas A, Charpentier G, Clauson P, Ravn GM, Roberts VL, Thorsteinsson B. Comparison of once-daily insulin detemir with NPH insulin added to a regimen of oral antidiabetic drugs in poorly controlled type 2 diabetes. Clin Ther. 2006 Oct;28(10):1569-81. doi: 10.1016/j.clinthera.2006.10.020.

  PMID: 17157113 BACKGROUND

• Mandosi E, Fallarino M, Rossetti M, Gatti A, Morano S. Waist circumference reduction after insulin detemir therapy in type 2 diabetes patients previously treated with NPH. Diabetes Res Clin Pract. 2009 May;84(2):e18-20. doi: 10.1016/j.diabres.2009.02.006. Epub 2009 Mar 17.

  PMID: 19297054 BACKGROUND

• Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.

  PMID: 33166419 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Fatty Liver

Interventions

Insulin Detemir

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 8, 2011
• Study Start: January 1, 2011
• Last Updated: March 8, 2011

Record last verified: 2010-06

Locations

CN (1)