Anti-inflammatory Status in DM2 Treated Patients

Phase 4

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: Metformin / alogliptin Oral Product; Drug: Metformin / Pioglitazone Pill; Drug: triple therapy

• Registration Number: NCT04392557
• Lead Sponsor: University of Catanzaro

Brief Summary

Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear. Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

Detailed Description

Diabetes mellitus Type 2 (DMT2) - a progressive insulin secretory defect on the background of insulin resistance - is one of the major risk factors for atherosclerosis, an inflammatory disease of the arterial wall, in which leukocytes and oxidized lipoproteins accumulate leading to formation of fatty streaks and atherosclerotic plaques. Atherosclerosis accounts for more than 600,000 deaths annually in the U.S. mainly due to acute myocardial infarction and stroke. Pharmacological therapy of DMT2 includes several drugs used as monotherapy, although combination therapy between metfomin plus thiazolidinediones (TZD) and/or dipeptidyl-peptidase 4 inhibitors (DPP4I) plus TDZ, may delay atherosclerosis progression even if the molecular mechanisms are not clear . Even if normoglycemia is achieved, DMT2 patients still displayed a higher risk for developing atherosclerosis suggesting that other mechanisms of the inflammatory status are involved

Study Timeline

• Study First Submitted: 2020-05-04
• Study First Submitted QC: 2020-05-15
• Study First Posted: 2020-05-19
• Study Start: 2020-07-01
• Status Verified: 2020-09
• Primary Completion: 2020-09-01
• Last Update Submitted: 2020-09-11
• Last Update Posted: 2020-09-16
• Study Completion: 2021-06-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• DMT2 patients were enrolled in presence of

  1. Age >35 and <75 years old
  2. Uncontrolled diabetes during treatment (glycosylated hemoglobin (HbA1c) > 75 mmol/mol )
  3. Combined therapy at least by 6 months.

Exclusion Criteria

1. HbA1c < 75 mmol/mol (9%);
2. History of drug abuse or alcohol abuse, averaging more than 30 gm/day (3 drinks per day) in the previous 10 years, or history of alcohol intake averaging greater than 10 gm/day (1 drink per day: 7 drinks per week) in the previous one year;
3. Estimated glomerular filtration rate (GFR) <30 ml/min (according to MDRD formula)
4. .Liver Failure
5. Recent history of Heart stroke, systemic infections, dehydration, lactic acidosis
6. Heart failure (NYHA I - IV)
7. Active bladder cancer or history of bladder cancer
8. macroscopic haematuria of unidentified nature
9. hypersensitivity to drug used (metformin, alogliptin, pioglitazone)
10. breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
triple therapy	Metformin / Pioglitazone Pill	metformin/pioglitazone (850 mg/15 mg every 12 hours)+alogliptin (12.5 mg every 12 hours) for 12 months
triple therapy	triple therapy	metformin/pioglitazone (850 mg/15 mg every 12 hours)+alogliptin (12.5 mg every 12 hours) for 12 months
metformin/alogliptin	Metformin / alogliptin Oral Product	metformin/alogliptin (850 mg/12.5 mg or 1000 mg/12.5 mg every 12 hours) for 12 months
triple therapy	Metformin / alogliptin Oral Product	metformin/pioglitazone (850 mg/15 mg every 12 hours)+alogliptin (12.5 mg every 12 hours) for 12 months
metformin/pioglitazone	Metformin / Pioglitazone Pill	metformin/pioglitazone (850 mg/15 mg every 12 hours) for 12 months

Primary Outcome Measures

Name	Time	Method
inflammatory miRNA	12 months	Change from Baseline at 12 months
side effects	12 months	statistically significant difference (P\<0.05) in the development of side effects between the groups, recorded using the Naranjo adverse drug reactions scale

Secondary Outcome Measures

Name	Time	Method
body weight	12 months	effects of each treatment on body mass index (kg/m\^2) (as indirect indexes of systemic inflammation and visceral adiposity).
Waist values	12 months	effects of each treatment on waist values (cm) (as indirect indexes of systemic inflammation and visceral adiposity).
drug interaction	12 months	statistically significant difference (P\<0.05) in the development of drug-drug interactions, recorded using the DIPS scale
Fasting blood glucose	12 months	effects of each treatment on fasting blood glucose (mg/dL) (as indexes of glucose metabolism);
HbA1c levels	12 months	effects of each treatment on HbA1c levels (percent) (as indexes of glucose metabolism);
liver function	12 months	alanine aminotransferase, aspartate aminotransferase, gamma glutamyl-transpeptidase levels, and total bilirubin levels (expressed as mg/dL) (as indexes of liver function).
cell count	12 months	effects of each treatment on white blood cell count expressed as cell/mm3 (as direct index of systemic inflammation)
lipid metabolism/atheroscelorisis	12 months	total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides levels (expressed as mg/dL) (as direct indexes of lipid metabolism and atheroscelorisis).

Trial Locations

Locations (1)

ASP Catanzaro; 🇮🇹 Catanzaro, Italy