Treatment of Latent Autoimmune Diabetes of the Adult

Study Overview
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Brief Summary
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The purpose of the study is to clarify whether patients classified as Latent autoimmune diabetes of the adult (LADA) benefit from early treatment with insulin added to per oral treatment and lifestyle measures.

Detailed Description
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Latent autoimmune diabetes of the adult (LADA) is usually defined as a form of diabetes where the onset of diabetes takes place approximately after 30 years of age, where there is presence of beta-cell directed antibodies (mostly anti-GAD) and where there is no clinical need for insulin treatment during the first 6 months after the diagnosis of diabetes. The aetiology and treatment of LADA patients is much less elucidated than is the case for type 1 diabetes (DM1) and type 2 diabetes (DM2). LADA constitutes about 10 % of the total diabetic population in many countries. LADA is therefore more common than insulin-requiring DM1. LADA patients lose beta-cell function faster than patients with DM2. Residual beta-cell function in DM1 is coupled to better metabolic control with lesser degree of hyperglycemia, lesser frequency of hypoglycaemic events and lesser diabetic complications. To retain beta-cell function in LADA patients is thus highly desirable. There are several strategies to retain beta cell function. One therapeutic strategy is to induce some degree of beta cell rest by treatment with exogenous insulin. Several observations indicate that such a strategy can have beneficial effects. This is a Scandinavian multicenter non-blinded clinical trial with 78 participants with newly diagnosed LADA. Participants will be randomized to either insulin- or per oral antidiabetic treatment. Participants will be followed up for 2 years after inclusion. Beta cell function and glycemic control will be monitored.

Official Title
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Is Beta Cell Rest by Insulin Treatment Beneficial Compared to State-of-the Art Enhancers of Insulin Secretion in Preserving Beta Cell Function in Subjects With Latent Autoimmune Diabetes of the Adult (LADA)?

Conditions
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Diabetes

Intervention / Treatment
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* Drug: metformin+ NPH insulin
* Drug: metformin + sitagliptin +/- repaglinide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes diagnosed during 0-3 years before entering the study. Age > or equal to 30 years < or equal to 75 years anti-GAD positivity fasting C-peptide > or equal to 0,3 ng/ml no need for insulin treatment by clinical judgement for at least 3 months following the diagnosis of diabetes. HbA1c > 15 % above the upper limit of normal Exclusion Criteria: Renal insufficiency (plasma creatinine > 150 mol/L) Severe retinopathy (proliferative or pre-proliferative) Severe cardiac disease (NYHA III-IV) Chronic severe illness judged by the investigator Females of reproductive age who wish to become pregnant during the study

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin + NPH Insulin<br>Patients are treated with metformin during the run-in period (3 months) and also after randomization. By randomization insulin treatment will be added in the form of injections of NPH insulin in the evenings. | Drug: metformin+ NPH insulin<br>* Metformin 500 mg + 500 mg + 1000 mg NPH insulin , initially 0.20 U/kg body weight.<br>* Other names: Januvia;|
| Active Comparator: Metformin + sitagliptin +/-repaglinid<br>Patients are treated with metformin during the run-in period (3 months) and also after randomization. By randomization sitagliptin tablets will be added.If HbA1c after 6 months of treatment is > 10 % above the upper limit of normal,then treatment with repaglinide tablets tree times daily at mealtimes will be added. | Drug: metformin + sitagliptin +/- repaglinide<br>* Metformin 500 mg + 500 mg + 1000 mg Sitagliptin 100 mg x 1 Repaglinide 1 mg x 3<br>* Other names: Novonorm;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin secretion | insulin secretion measured by fasting and glucagon-stimulated C-peptide | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycemic control | glycemic control (HbA1c) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Latent autoimmune diabetes, adults, Beta cell rest, Insulin secretion