Clinical trial NCT04945070: INSULIN THERAPY DE-INTENSIFICATION WITH iGlarLixi
Official title: INSULIN THERAPY DE-INTENSIFICATION WITH iGlarLixi
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Type 2 Diabetes Treated With Insulin
Lead sponsor: Institute for Clinical and Experimental Medicine
Sponsor class: OTHER_GOV
First posted: 2021-06-30
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intensive insulin therapy using multiple daily injections (MDI) constitutes the most intense type of regimen in type 2 diabetes mellitus (T2D). Although highly effective in lowering blood glucose, it can also increase the risk of hypoglycemia, promote weight gain and cause significant treatment burden for the patients. As demonstrated by a number of clinical studies, overtreatment is a common and generally unrecognized problem in patients with T2D; nevertheless, medication de-escalation is still infrequent in everyday clinical practice. IGlarLixi is a once-daily fixed-ratio combination (FRC) of a basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1 RA), which can offer similar efficacy in glucose control with lower rates of hypoglycemia and smaller weight gain that basal insulin regimens. The aim of our randomised, controlled study is to examine prospectively the safety and efficacy of de-escalating MDI regimens to iGlarLixi in T2D adult patients.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Adult participants with T2DM
* Participants who have been treated with a an MDI regimen comprising of at least 3 doses of prandial insulin per day and one dose of basal insulin per day for at least 3 months before the screening visit,
* Participants treated with metformin (unless intolerance to metformin use is present) ± SGLT2i at stable doses for at least 3 months prior screening.
* Total daily insulin dose ≤ 0.8 IU/kg,
* Fasting C peptide above the lower limit of the normal range,
* HbA1c at screening visit ≤ 75 mmol/mol (9%) as measured by local laboratory,
* HbA1c at screening visit 76-86 mmol/mol (9.1-10%) as measured by local laboratory in case of proven non-compliance with MDI regimen

Exclusion Criteria:

* At screening visit, age under legal age of adulthood (\<18 years),
* History of other diabetes than T2DM (type 1 diabetes T1DM, monogenic, secondary..)
* Use of any oral or injectable glucose-lowering agents other than those stated in the inclusion criteria within the last 3 months before screening,
* History of discontinuation of a previous treatment with GLP-1 RA for safety/tolerability reasons or lack of efficacy,
* Use of systemic glucocorticoids (excluding topical and inhaled forms) for a total duration of 1 week or more within 3 months prior to screening visit,
* Comorbidity (such as but not limited to rheumatoid arthritis) with continuous, intermittent or expected systemic glucocorticoid therapy during the next 30 weeks after screening visit,
* Use of weight loss drugs within 3 months prior to screening visit,
* Use of any investigational drug within 1 month or 5 half-lives, whichever is longer, prior to screening visit,
* Within the last 3 months prior to screening visit: history of stroke, pulmonary embolism, myocardial infarction, unstable angina, or heart failure requiring hospitalization,
* Chronic hear failure NYHA stages III-IV
* Acute or chronic liver failure - established diagnosis of acute or chronic liver failure (Child-Pugh 3, MELD≥15) or liver cirrhosis
* Planned coronary, carotid or peripheral artery revascularisation procedures to be performed during the study period,
* Known history of drug or alcohol abuse within 6 months prior to the time of screening visit,
* Active malignancy
* Anaemia with haemoglobin \< 100 g/l at baseline
* Participants with conditions/concomitant diseases making them non evaluable for the efficacy endpoints (eg, hemoglobinopathy or hemolytic anemia, receipt of blood or plasma products within the last 3 months prior to the screening visit),
* Participants with conditions/concomitant diseases precluding their safe participation in this study (eg, active malignant tumor, major systemic diseases, presence of clinically significant diabetic retinopathy or presence of macular edema likely to require treatment within the study period, etc.),
* Impossibility to meet specific protocol requirements (eg, scheduled visits, participants unable to fully understand participant's study documents and to complete them, etc.),
* Uncooperative or any condition that could make the participant potentially non-compliant to the study procedures (eg, participant unable or unwilling to do self-injections or blood glucose monitoring using the sponsor-provided blood glucose meter at home, etc.);
* Participant is the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
* Participation in another clinical trial
* Pregnancy or lactation,
* Women of childbearing potential not protected by highly effective contraceptive method of birth control (definition see section 10.1.1.1),
* Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to): gastroparesis, unstable (ie, worsening) or not controlled (ie, prolonged nausea and vomiting) gastroesophageal reflux disease requiring medical treatment, within 6 months prior to the time of screening visit or history of surgery affecting gastric emptying
* History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy had now been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy,
* Personal or immediate family history of MTC or genetic condition that predisposes to MTC (eg, multiple endocrine neoplasia syndromes),
* Participant who has a renal function impairment with creatinine clearance \<30 mL/min (using the eGFR) or end-stage renal disease (ie. CKD stage IV or V),
* History of allergic reaction to any GLP-1 RA in the past

Primary outcomes:
measure: HbA1C
timeFrame: 6 months
Secondary outcomes:
measure: Hypoglycemia
timeFrame: 6 months
measure: Compliance
timeFrame: 6 months
measure: Fasting plasma glucose
timeFrame: 6 months
measure: Postprandial plasma glucose
timeFrame: 6 months
measure: Glycemic variability
timeFrame: 6 months
measure: Time in target range of 3.9-10 mmol/l
timeFrame: 6 months
measure: Body weight
timeFrame: 6 months
measure: Treatment Satisfaction
timeFrame: 6 months
Other outcomes:
measure: ALT
timeFrame: 6 months
measure: hsCRP
timeFrame: 6 months
Locations:
city: Prague
country: Czechia
facility: Institute for Clinical and Experimental Medicine
Study officials:
References: