Treatment of Latent Autoimmune Diabetes of the Adult (LADA)

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)?

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.

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Drug: metformin+ NPH insulin; Drug: metformin + sitagliptin +/- repaglinide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • Valdemar Grill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Metformin + NPH Insulin; 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; Metformin 500 mg + 500 mg + 1000 mg NPH insulin , initially 0.20 U/kg body weight.; Other Names: Januvia; Insulatard
Active Comparator: Metformin + sitagliptin +/-repaglinid; 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; Metformin 500 mg + 500 mg + 1000 mg Sitagliptin 100 mg x 1 Repaglinide 1 mg x 3; Other Names: Novonorm

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Investigators: Principal Investigator: Valdemar Grill, med phd, Department of Cancer Research and Molecular Medicine

Publications and helpful links

General Publications

• Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Bjorklund A. Investigating optimal beta-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019 Oct;21(10):2219-2227. doi: 10.1111/dom.13797. Epub 2019 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2009
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: June 8, 2010
• First Submitted That Met QC Criteria: June 8, 2010
• First Posted (Estimate): June 9, 2010

Study Record Updates

• Last Update Posted (Actual): January 10, 2020
• Last Update Submitted That Met QC Criteria: January 8, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: adults; Insulin secretion; Latent autoimmune diabetes; Beta cell rest
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate; Insulin, Isophane; Isophane Insulin, Human; Isophane insulin, beef; Repaglinide
• Other Study ID Numbers: LADA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No