Condition category
Nutritional, Metabolic, Endocrine
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Sinead Brophy


Contact details

School of Medicine
Swansea University
Singleton Park
United Kingdom
+44 (0)1792 602058

Additional identifiers

EudraCT number

2006-004662-14 number


Protocol/serial number

EudraCT 2006-004662-14 AND S06 GenMed601

Study information

Scientific title


LIT (LADA Insulin Trial)

Study hypothesis

Treatment for Latent Autoimmune Diabetes in Adults (LADA) should be that used for type 1 diabetes (insulin) rather than type 2 diabetes (tablets) in order to maintain glucose control (HbA1c) and natural insulin production (C-peptide).

Ethics approval

Multi-Centre Research Ethics Committee (MREC) for Wales, 22/02/2007, ref: 07/MRE09/8

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Latent autoimmune diabetes in adults


1. Treatment group one - insulin:
Patients will be given advice on diet, exercise and lifestyle and will be started on NovoMix 30, one dose of 6 U at the evening/main meal. Dose will be adjusted in increments of 2 - 6 U depending on fasting glucose level. Adjustment of breakfast and/or evening meal dose (i.e. evening dose for pre-breakfast glucose and morning dose for pre evening meal glucose) will be performed once a week as follows:

a. Less than 3.0 Mmol/l or severe hypoglycaemia: -4 U
b. 3.1 - 4.4 Mmol/l: -2 U
c. 4.5 - 6.0 Mmol/l: No change
d. 6.1 - 7.8 Mmol/l: +2 U
e. 7.9 - 10.0 Mmol/l: +4 U
f. Greater than 10.0 Mmol/l: +6 U

When total dose equals 16 U patient will be started on 4 U with breakfast and continue with 16 units with evening meal. Breakfast and/or evening meal dose will be adjusted where necessary at increments of 2 - 6 U depending on fasting and/or pre-evening meal glucose level. Patient needs to keep a daily diary of insulin doses taken.

2. Treatment group two - tablets:
a. Step one: patients not treated with tablets will be given a three months trial of lifestyle modification including advice on diet, exercise and smoking. If HbA1c remains above 7% patients will progress to step two. Patients will be progressed to step two if their General Practitioner (GP) has already put them on metformin (put in at number of metformin tables that GP has recommended) or sulphonylurea or if their baseline HbA1c is above 8% (patients will start on one 500 mg tablet per day). This means that sulphonylurea will be discontinued in all patients. Patients on step one will be progressed to step two before the three-month period if they have already had a three-month period of diet before starting the study AND during phone contact they report to be symptomatic (thirst, fatigue, polyuria) and unwell. In these cases, patients may be invited to attend clinic before the three-month period to be given metformin
b. Step two: lifestyle modification and Metformin. If the patient has an HbA1c of 7% - 7.5% they start on 500 mg x 1 per day for the next three months. If the HbA1c is 7.6% - 8.0% they would start the first week on 500 mg x 1 day and then for the remaining period of the three months will take 500 mg x 2 per day. If the HbA1c is above 8.0% then patient will be on 500 mg x 3 per day. This will be titrated at the rate of 500 mg x 1 for the first week, 500 mg x 2 for the second week and 500 mg x 3 for the remaining time of the three-month period. If unable to tolerate metformin then the participant will be given Glucophage SR and if unable to tolerate this they will then progress to Step three. If HbA1c remains above 7% then those on one tablet per day will be moved to two tablets per day, those on two tablets per day will be moved to three tablets per day, those on three tablets per day will be move to maximum dose of 2 g per day. If after three months the HbA1c is above 7% even with maximum dose, then progress to Step three. If during telephone contact the patient reports symptoms then they may be titrated up. In summary, patients will be have their HbA1c evaluated every three months and will be titrated accordingly
c. Step three: lifestyle modification and Glitazone (Roseglitazone). Patients with an HbA1c of above 7% will be given 4 mg once per day for three months. If after a three-month period the HbA1c remains above 7% then titrate to maximal dose of 4 mg twice per day with or without Metformin. If HbA1c remains above 7% for an additional three months then move to step four. Therefore, glitazone monotherapy will be used if Metformin intolerant otherwise glitazone will be added to the metformin (as per standard practice)
d. Step four: lifestyle modification and insulin therapy (oral agents will be stopped). Titration will be based on fasting blood glucose level. The initiation of insulin will the same as for the insulin arm and will follow the protocol detailed above

Intervention type



Not Applicable

Drug names

Metformin, glitazone, insulin

Primary outcome measures

To examine the effect of standard treatment for type one (insulin [NovoMix 30] therapy) compared to standard treatment for type two diabetes (tablets) on:
1. Change in fasting serum C-peptide level over 24 months in patients with LADA, and
2. Change in HbA1c level over 24 months in patients with LADA

Secondary outcome measures

To assess the effect of standard type one treatment (insulin) on:
1. Average number of times the fasting plasma glucose level is above 8 mmol/l (141 mg/dl)
2. Quality of life
3. Proportion of patients with insulin dependence (as judged by C peptide level)
4. GAD antibody level
5. Homeostasis Model Assessment (HOMA)
6. Adverse events (particularly hypoglycaemic events)
7. Weight/blood pressure/total cholesterol and inflammatory markers in LADA patients compared to standard type two diabetes treatment

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Male, non-fertile female (i.e., post menopausal, post hysterectomy, or sterilised by tubal ligation) or female of childbearing potential using a medically approved birth control method
2. The patient has a diagnosis of diabetes mellitus according to World Health Organisation (WHO) classification
3. The patient has a positive Glutamic Acid Decarboxylase (GAD) antibody test of 101 units or more on two separate occasions
4. Aged 18 years or more
5. Not on insulin within one month of diagnosis
6. Written informed consent to participate in the study
7. Ability to comply with all study requirements

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Pregnant or breast-feeding females and females who plan pregnancy or breast-feeding during the course of the study
2. A history of:
2.1. Diabetes that is a result of pancreatic injury, or secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly
2.2. Acute metabolic diabetic complications such as ketoacidosis or hyperosmolar state (coma) within the past six months
3. Acute infections, which may affect blood glucose control within four weeks prior to visit one
4. Malignancy including leukaemia and lymphoma (not including basal cell skin cancer) within the last five years
5. The patient has a known immune deficiency from any disease, or a condition associated with an immune deficiency
6. The patient is receiving immunosuppressive or immunomodulating agents or cytotoxic therapy, or any medication that, in the opinion of the site investigator, might interfere with the study
7. Any of the following significant laboratory abnormalities:
7.1. Patients with severe renal failure as defined previous renal transplant or currently having renal dialysis or Glomerular Filtration Rate (GFR) less than 30
7.2. Clinically significant laboratory abnormalities, confirmed by repeat measurement, that may interfere with the assessment of safety and/or efficacy of the study drug, other than hyperglycaemia and glycosuria at visit one
7.3. Severe ketonuria (+++ on urine sticks testing; ++ on repeated urine sticks testing)
8. The patient is a known or suspected drug abuser
9. The patient has chronic hepatitis or liver cirrhosis, or any other chronic liver disease
10. The patient is known to test positive for hepatitis B antigens or hepatitis C antibodies
11. The patient is known to test positive for Human Immunodeficiency Virus (HIV) antibodies
12. The patient has any significant diseases or conditions, including psychiatric disorders and substance abuse that, in the opinion of the site investigator, are likely to affect the patient's response to treatment or their ability to complete the study
13. The patient has chronic haematological disease
14. The patient has had a severe blood loss (greater than or equal to 400 mL, e.g., blood donation) within two months before the first dosing of the study medication
15. The patient has known proliferative retinopathy
16. Patient has had stage three to four heart failure
17. The patient is participating in another research study which may affect the results of this trial

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

School of Medicine
United Kingdom

Sponsor information


Swansea NHS Trust (UK)

Sponsor details

Central Clinic
Trinity Buildings
21 Orchard Street
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Novo Nordisk Ltd (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2008 protocol in:

Publication citations

  1. Protocol

    Brophy S, Davies H, Bain S, Stephens JW, Cheung WY, Richards K, Wareham K, Beaverstock C, Lloyd J, Page D, Williams M, Russell I, Williams R, Randomized, controlled, parallel-group prospective study to investigate the clinical effectiveness of early insulin treatment in patients with latent autoimmune diabetes in adults., BMC Endocr Disord, 2008, 8, 8, doi: 10.1186/1472-6823-8-8.

Additional files

Editorial Notes