Real-world Evaluation of GLP-1 Receptor Agonists (GLP-1RA) on Efficacy and Persistence, Adherence and Therapeutic Inertia Among Type 2 Diabetes Adults With Obesity

NCT05535322 | Completed DMC FDA Drug

• 1 other identifier: GLP-1RA in T2D
• Study Type: observational
• Target: 26,944
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes (T2D) is a progressive chronic condition associated with a high morbi-mortality that has a considerable impact on healthcare resources. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are incretin mimetics that have been shown to improve glycemic control with a low associated risk of hypoglycemia. Additionally, previous studies have linked the use of GLP-1RA with a reduction in the risk of cardiovascular events and kidney disease progression. Despite these positive results, GLP1-RA´s prescription, following the failure of treatment with metformin monotherapy or dual therapy, remains low in Spain compared to other countries in our milieu. Furthermore, the use of this therapeutic class is not homogeneous across the different autonomous communities in Spain, and, no objective justification for these differences seems to exist. Consequently, there is a need to understand which are the benefits associated with the use of GLP-1RA, versus intensification with other oral agents, in real-life conditions. In this study, the impact of the use of GLP-1RA on clinical outcomes such as all-cause mortality, cardiovascular and renal outcomes as well as severe hypoglycemia will be evaluated based on the analysis of longitudinal databases that collect the variables of interest generated in a real-life scenario. In addition, both persistence and adherence to treatment in patients treated with GLP-1RA and its impact on the clinical outcomes of interest will be studied. Finally, therapeutic inertia will be analyzed. All these data will contribute to generating cost-effective strategies aimed at improving health outcomes among T2D patients in our setting, reinforcing persistence and adherence to the prescribed treatment, and reducing therapeutic inertia in this group of patients. Since the use of GLP-1RA versus intensification with other oral agents has been associated with better glycemic control, and, when compared to intensification with basal insulin, with a lower incidence of severe hypoglycemia, we hypothesized that T2D adults treated with GLP-1RA would present a lower incidence of cardiovascular and renal outcomes and fewer hospitalizations due to severe hypoglycemia events as well as a decreased all-cause mortality. On the other hand, patients on GLP-1RA who would present greater persistence and adherence to treatment should experience fewer cardiovascular and renal outcomes and lower mortality compared to those with less persistence and adherence. Finally, it is possible that the type of GLP-1RA and the mode of administration, weekly versus daily, may influence adherence, persistence and therapeutic inertia in this group of patients.

Conditions

Type 2 Diabetes; Obesity

Outcome Measures

Primary Outcomes (1)

• Major acute cardiovascular events

  In this work, this composite includes patients suffering from non-fatal acute myocardial infarction (AMI) and non-fatal stroke, transient ischemic attack (TIA), all-cause death, and, heart failure events occurring during the study period (from inclusion in the study until the event or the end of the study period, whichever came first).

  From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first.

Secondary Outcomes (11)

• Major acute cardiovascular events without heart failure

  From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first.

• AMI

  From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first.

• Stroke

  From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first.

• Heart Failure

  Through study completion (from inclusion in the study until the event or the end of the study period, whichever came first)

• all-cause death

  From inclusion in the study, starting from 01/01/2014, until the event or the end of the study, on 31/12/2019, whichever came first.

Study Arms (4)

GLP-1RA

All GLP-1RA users: all T2D adults treated with GLP-1RA or initiating a GLP-1RA during the study period

Drug: GLP-1RA

SGLT2i

SGLT2 inhibitors users with no GLP-1RA prescription: all T2D adults treated with SGLT2i or initiating treatment with SGLT2i during the study period and who were not treated with a GLP-1RA

Drug: SGLT2i

Insulin

Insulin users with no GLP-1RA and/or SGLT2i prescriptions: all T2D adults treated with insulin or initiating insulin treatment during the study period and who were not treated with GLP-1RA/SGLT2i

Drug: Insulin

Miscellany

Other glucose-lowering agents users: all T2D adults who were not treated with GLP-1RA and/or SGLT2i and/or insulin during the study period.

Drug: Miscellany

Interventions

GLP-1RA DRUG

All T2D adults treated with Glucagon-like peptide-1 receptor agonists (GLP-1RA) or initiating a GLP-1RA during the study period

GLP-1RA

SGLT2i DRUG

SGLT2 inhibitors users with no GLP-1RA prescription: all T2D adults treated with Sodium/glucose cotransporter-2 inhibitors (SGLT2i) or initiating treatment with SGLT2i during the study period and who were not treated with a GLP-1RA

SGLT2i

Insulin DRUG

Insulin users with no GLP-1RA and/or SGLT2i prescriptions: all T2D adults treated with insulin or initiating insulin treatment during the study period and who were not treated with GLP-1RA/SGLT2i

Insulin

Miscellany DRUG

Other glucose-lowering agents users: all T2D adults who were not treated with GLP-1RA and/or SGLT2i and/or insulin during the study period and who were treated with other glucose-lowering agents during the study period

Miscellany

Eligibility Criteria

• Age: 18 Years - 125 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All identified adults with type 2 diabetes registered in the Population Information System (SIP) of the Valencian Community and corresponding to the Valencia Clínico-La Malvarrosa Health Department who were diagnosed before the end of the study period were included. Type 2 diabetes (T2D) diagnosis was defined according to the International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification (ICD-9-CM, ICD-10-CM) codes. To exclude temporary treatment effects due to short-term use of the antidiabetic treatments, only individuals in the study groups with at least a 6-month prescription were included in the analyses.

You may qualify if:

• Adults with type 2 diabetes
• Individuals with at least a 6-month prescription

You may not qualify if:

• Individuals below 18
• Individuals with less than a 6-month prescription

Sponsors & Collaborators

• Ana Palanca: lead

Study Sites (1)

INCLIVA

Valencia, 46010, Spain

Location

Related Publications (18)

• Blonde L, Raccah D, Lew E, Meyers J, Nikonova E, Ajmera M, Davis KL, Bertolini M, Guerci B. Treatment Intensification in Type 2 Diabetes: A Real-World Study of 2-OAD Regimens, GLP-1 RAs, or Basal Insulin. Diabetes Ther. 2018 Jun;9(3):1169-1184. doi: 10.1007/s13300-018-0429-x. Epub 2018 Apr 19.

  PMID: 29675797 BACKGROUND

• Carls GS, Tuttle E, Tan RD, Huynh J, Yee J, Edelman SV, Polonsky WH. Understanding the Gap Between Efficacy in Randomized Controlled Trials and Effectiveness in Real-World Use of GLP-1 RA and DPP-4 Therapies in Patients With Type 2 Diabetes. Diabetes Care. 2017 Nov;40(11):1469-1478. doi: 10.2337/dc16-2725. Epub 2017 Aug 11.

  PMID: 28801475 BACKGROUND

• Chatterjee S, Davies MJ, Khunti K. What have we learnt from "real world" data, observational studies and meta-analyses. Diabetes Obes Metab. 2018 Feb;20 Suppl 1:47-58. doi: 10.1111/dom.13178.

  PMID: 29364585 BACKGROUND

• Conget I, Mauricio D, Ortega R, Detournay B; CHADIG Study investigators. Characteristics of patients with type 2 diabetes mellitus newly treated with GLP-1 receptor agonists (CHADIG Study): a cross-sectional multicentre study in Spain. BMJ Open. 2016 Jul 26;6(7):e010197. doi: 10.1136/bmjopen-2015-010197.

  PMID: 27466235 BACKGROUND

• Divino V, Boye KS, Lebrec J, DeKoven M, Norrbacka K. GLP-1 RA Treatment and Dosing Patterns Among Type 2 Diabetes Patients in Six Countries: A Retrospective Analysis of Pharmacy Claims Data. Diabetes Ther. 2019 Jun;10(3):1067-1088. doi: 10.1007/s13300-019-0615-5. Epub 2019 Apr 26.

  PMID: 31028689 BACKGROUND

• Divino V, DeKoven M, Khan FA, Boye KS, Sapin H, Norrbacka K. GLP-1 RA Treatment Patterns Among Type 2 Diabetes Patients in Five European Countries. Diabetes Ther. 2017 Feb;8(1):115-128. doi: 10.1007/s13300-016-0224-5. Epub 2017 Jan 9.

  PMID: 28070733 BACKGROUND

• Fadini GP, Frison V, Rigato M, Morieri ML, Simioni N, Tadiotto F, D'Ambrosio M, Paccagnella A, Lapolla A, Avogaro A. Trend 2010-2018 in the clinical use of GLP-1 receptor agonists for the treatment of type 2 diabetes in routine clinical practice: an observational study from Northeast Italy. Acta Diabetol. 2020 Mar;57(3):367-375. doi: 10.1007/s00592-019-01445-z. Epub 2019 Oct 31.

  PMID: 31673896 BACKGROUND

• Fu AZ, Qiu Y, Davies MJ, Radican L, Engel SS. Treatment intensification in patients with type 2 diabetes who failed metformin monotherapy. Diabetes Obes Metab. 2011 Aug;13(8):765-9. doi: 10.1111/j.1463-1326.2011.01405.x.

  PMID: 21457427 BACKGROUND

• Gaede P, Oellgaard J, Carstensen B, Rossing P, Lund-Andersen H, Parving HH, Pedersen O. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia. 2016 Nov;59(11):2298-2307. doi: 10.1007/s00125-016-4065-6. Epub 2016 Aug 16.

  PMID: 27531506 BACKGROUND

• Guerci B, Charbonnel B, Gourdy P, Hadjadj S, Hanaire H, Marre M, Verges B. Efficacy and adherence of glucagon-like peptide-1 receptor agonist treatment in patients with type 2 diabetes mellitus in real-life settings. Diabetes Metab. 2019 Dec;45(6):528-535. doi: 10.1016/j.diabet.2019.01.006. Epub 2019 Jan 21.

  PMID: 30677504 BACKGROUND

• Hernandez AF, Green JB, Janmohamed S, D'Agostino RB Sr, Granger CB, Jones NP, Leiter LA, Rosenberg AE, Sigmon KN, Somerville MC, Thorpe KM, McMurray JJV, Del Prato S; Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018 Oct 27;392(10157):1519-1529. doi: 10.1016/S0140-6736(18)32261-X. Epub 2018 Oct 2.

  PMID: 30291013 BACKGROUND

• Kristensen SL, Rorth R, Jhund PS, Docherty KF, Sattar N, Preiss D, Kober L, Petrie MC, McMurray JJV. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019 Oct;7(10):776-785. doi: 10.1016/S2213-8587(19)30249-9. Epub 2019 Aug 14.

  PMID: 31422062 BACKGROUND

• Lin J, Lingohr-Smith M, Fan T. Real-world medication persistence and outcomes associated with basal insulin and glucagon-like peptide 1 receptor agonist free-dose combination therapy in patients with type 2 diabetes in the US. Clinicoecon Outcomes Res. 2016 Dec 22;9:19-29. doi: 10.2147/CEOR.S117200. eCollection 2017.

  PMID: 28053550 BACKGROUND

• Leiter LA, Bain SC, Bhatt DL, Buse JB, Mazer CD, Pratley RE, Rasmussen S, Ripa MS, Vrazic H, Verma S. The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials. Diabetes Obes Metab. 2020 Sep;22(9):1690-1695. doi: 10.1111/dom.14079. Epub 2020 Jun 3.

  PMID: 32372454 BACKGROUND

• Khunti K, Gomes MB, Pocock S, Shestakova MV, Pintat S, Fenici P, Hammar N, Medina J. Therapeutic inertia in the treatment of hyperglycaemia in patients with type 2 diabetes: A systematic review. Diabetes Obes Metab. 2018 Feb;20(2):427-437. doi: 10.1111/dom.13088. Epub 2017 Oct 1.

  PMID: 28834075 BACKGROUND

• Pasternak B, Wintzell V, Eliasson B, Svensson AM, Franzen S, Gudbjornsdottir S, Hveem K, Jonasson C, Melbye M, Svanstrom H, Ueda P. Use of Glucagon-Like Peptide 1 Receptor Agonists and Risk of Serious Renal Events: Scandinavian Cohort Study. Diabetes Care. 2020 Jun;43(6):1326-1335. doi: 10.2337/dc19-2088. Epub 2020 Apr 15.

  PMID: 32295809 BACKGROUND

• Pineda ED, Liao IC, Godley PJ, Michel JB, Rascati KL. Cardiovascular Outcomes Among Patients with Type 2 Diabetes Newly Initiated on Sodium-Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Other Antidiabetic Medications. J Manag Care Spec Pharm. 2020 May;26(5):610-618. doi: 10.18553/jmcp.2020.26.5.610.

  PMID: 32347181 BACKGROUND

• Palanca A, Ampudia-Blasco FJ, Calderon JM, Sauri I, Martinez-Hervas S, Trillo JL, Redon J, Real JT. Real-World Evaluation of GLP-1 Receptor Agonist Therapy Persistence, Adherence and Therapeutic Inertia Among Obese Adults with Type 2 Diabetes. Diabetes Ther. 2023 Apr;14(4):723-736. doi: 10.1007/s13300-023-01382-9. Epub 2023 Feb 27.

  PMID: 36847952 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Coordinator

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: September 10, 2022
• Study Start: January 1, 2014
• Primary Completion: December 31, 2019
• Study Completion: September 1, 2022
• Last Updated: September 28, 2022

Record last verified: 2022-09

Locations

ES (1)