GLP-1 REceptor Agonists and Real World EvIdeNce

NCT03959865 | Unknown

• 1 other identifier: 4462/AO/18
• Study Type: observational
• Target: 6,000
• Locations: 1 country
• Sites: 6

Brief Summary

Glucagon-like peptide-1 receptor agonists (GLP-1RA) are powerful second-line agents for the treatment of type 2 diabetes. GLP-1RA have bene marketed in 2010 in Italy and years of experience have accumulated for the treatment with this class of drugs. Cardiovascular outcome trials have shown that type 2 diabetic patients with established cardiovascular disease treated with GLP-1RA have a lower risk of future cardiovascular events. In this real world study, we wish to evaluate retrospectively the effectiveness and persistence on treatment of GLP-1RA therapy in patients with type 2 diabetes from 2010 to 2018. Effectiveness endpoints will be glycemic (fasting plasma glucose and HbA1c) and extra-glycemic (body weight and blood pressure). Data from diabetes outpatient clinics in North East Italy will be automatically extracted from electronic chart records and collected into a unique database. Different groups of GLP-1RA therapies will be compared:

• Long-acting (e.g. dulaglutide and exenatide once weekly) versus short acting (exenatide, liraglutide and lixisenatide)
• Fixed versus flexible combinations of GLP-1RA and basal insulin.
• GLP-1RA with similarities to human GLP-1 (e.g. liraglutide) versus exendin-based GLP-1RA (e.g. exenatide).

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• HbA1c

  Change in HbA1c from baseline to end of follow-up

  3-12 months

Secondary Outcomes (3)

• Weight

  3-12 months

• Blood pressure

  3-12 months

• Persistence

  3-12 months

Study Arms (6)

Long-acting GLP-1RA

Patients who have been treated with weekly GLP-1RA (exenatide once weekly or dulaglutide)

Drug: Long-acting GLP-1RA

Short-acting GLP-1RA

Patients who have been treated with daily GLP-1RA (exenatide bid or liraglutide or lixisenatide)

Drug: Short-acting GLP-1RA

Human GLP-1 based GLP-1RA

Patients who have been treated with GLP-1RA based on human GLP-1 (dulaglutide or liraglutide)

Drug: Human-based GLP-1RA

Exendin-based GLP-1RA

Patients who have been treated with weekly GLP-1RA (exenatide or lixisenatide)

Drug: Exendin-based GLP-1RA

Fixed ratio combination of BI/GLP-1RA

Patients who have been treated with a fixed ratio combination of GLP-1RA and basal insulin (BI), such as IdegLira (insulin degludec / liraglutide) or IglarLixi (insulin glargine / lixisenatide)

Drug: Fixed ratio BI/GLP-1RA combination

Flexible combination of BI/GLP-1RA

Patients who have been treated with any GLP-1RA in combination with any basal insulin (BI)

Drug: Flexible BI/GLP-1RA combination

Interventions

Long-acting GLP-1RA DRUG

Dulaglutide 0.75 or 1.5 mg /week or Exenatide once weekly 2 mg

Long-acting GLP-1RA

Short-acting GLP-1RA DRUG

Liraglutide 0.6 mg or 1.2 mg or 1.8 mg / day or exenatide 10 mcg or 20 mcg bid or lixisenatide 10 mcg or 20 mcg / day.

Short-acting GLP-1RA

Human-based GLP-1RA DRUG

Liraglutide 0.6 mg or 1.2 mg or 1.8 mg / day or dulaglutide 0.75 or 1.5 mg / week

Human GLP-1 based GLP-1RA

Exendin-based GLP-1RA DRUG

Exenatide 10 mcg or 20 mcg day or 2 mg / week or lixisenatide 10 mcg or 20 mcg / day.

Exendin-based GLP-1RA

Fixed ratio BI/GLP-1RA combination DRUG

Insulin degludec / liraglutide (0.036/U) or insulin glargine / lixisenatide (0.5 mcg/U)

Fixed ratio combination of BI/GLP-1RA

Flexible BI/GLP-1RA combination DRUG

GLP-1RA (Liraglutide or dulaglutide or exenatide or lixisenatide) and basal insulin (BI, glargine, degludec, detemir, NPH insulin)

Flexible combination of BI/GLP-1RA

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Type 2 diabetic patients attending diabetes specialist clinics in North East Italy.

You may qualify if:

• Type 2 diabetes
• Diabetes duration of at least 1 year
• Initiated on a GLP-1RA during the data collection period

You may not qualify if:

• Type 1 diabetes
• Previous therapy with a GLP-1RA before the data collection period

Sponsors & Collaborators

• University of Padova: lead
• Azienda Ospedaliera di Padova: collaborator

Study Sites (6)

Servizio di Diabetologia UOC Medicina Generale

Cittadella, Padova, 35013, Italy

Location

U.O.S Diabetologia, Ospedale di Schiavonia

Monselice, Padova, 35043, Italy

Location

U.O. Diabetologia ULSS2

Pieve di Soligo, Treviso, 31053, Italy

Location

U.O. Diabetologia e Dietetica ULSS6

Padua, 35100, Italy

Location

Azienda Ospedaliera di Padova

Padua, 35128, Italy

Location

Diabetologia ULSS2

Treviso, 31100, Italy

Location

Related Publications (6)

• Lovshin JA, Drucker DJ. Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol. 2009 May;5(5):262-9. doi: 10.1038/nrendo.2009.48.

  PMID: 19444259 BACKGROUND

• Bethel MA, Patel RA, Merrill P, Lokhnygina Y, Buse JB, Mentz RJ, Pagidipati NJ, Chan JC, Gustavson SM, Iqbal N, Maggioni AP, Ohman P, Poulter NR, Ramachandran A, Zinman B, Hernandez AF, Holman RR; EXSCEL Study Group. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol. 2018 Feb;6(2):105-113. doi: 10.1016/S2213-8587(17)30412-6. Epub 2017 Dec 6.

  PMID: 29221659 BACKGROUND

• Davies MJ, D'Alessio DA, Fradkin J, Kernan WN, Mathieu C, Mingrone G, Rossing P, Tsapas A, Wexler DJ, Buse JB. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018 Dec;41(12):2669-2701. doi: 10.2337/dci18-0033. Epub 2018 Oct 4.

  PMID: 30291106 BACKGROUND

• Abd El Aziz MS, Kahle M, Meier JJ, Nauck MA. A meta-analysis comparing clinical effects of short- or long-acting GLP-1 receptor agonists versus insulin treatment from head-to-head studies in type 2 diabetic patients. Diabetes Obes Metab. 2017 Feb;19(2):216-227. doi: 10.1111/dom.12804. Epub 2016 Nov 29.

  PMID: 27717195 BACKGROUND

• Singh S, Wright EE Jr, Kwan AY, Thompson JC, Syed IA, Korol EE, Waser NA, Yu MB, Juneja R. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes Obes Metab. 2017 Feb;19(2):228-238. doi: 10.1111/dom.12805. Epub 2016 Dec 5.

  PMID: 27717130 BACKGROUND

• Morieri ML, Rigato M, Frison V, Simioni N, D'Ambrosio M, Tadiotto F, Paccagnella A, Lapolla A, Avogaro A, Fadini GP. Fixed versus flexible combination of GLP-1 receptor agonists with basal insulin in type 2 diabetes: A retrospective multicentre comparative effectiveness study. Diabetes Obes Metab. 2019 Nov;21(11):2542-2552. doi: 10.1111/dom.13840. Epub 2019 Aug 12.

  PMID: 31364233 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Gian Paolo Fadini, MD PhD

  University of Padova

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2019
• First Posted: May 22, 2019
• Study Start: December 19, 2018
• Primary Completion: February 11, 2019
• Study Completion: May 31, 2019
• Last Updated: May 22, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (6)