Comparative Cardiovascular Effectiveness of GLP-1 RAs vs. Insulin in Early-Onset Type 2 Diabetes

NCT06913881 | Completed FDA Drug

• 1 other identifier: Karolinska Institutet (KI)
• Study Type: observational
• Target: 92,100
• Locations: 1 country
• Sites: 1

Brief Summary

The incidence of early-onset type 2 diabetes (T2D) is increasing globally. People with early-onset T2D have faster beta-cell deterioration and more aggressive diabetes progression than their late-onset counterparts. However, there is no specific treatment guideline tailored to the early-onset population. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) belong to a new class of glucose-lowering drugs that have been shown to promote weight loss and reduce incidence of cardiovascular diseases (CVD) in individuals with (mostly late-onset) T2D. Given the much higher prevalence of obesity, a key risk factor for CVD, in early-onset T2D, the cardiovascular benefits of the GLP-1 RA may be more pronounced in early-onset than in late-onset T2D. In addition, insulin use is highly prevalent in people with early-onset T2D. However, no randomized controlled trial (RCT) has evaluated the comparative effectiveness of GLP-1 RA and insulin on CVD incidence and CVD risk factors in this population. Our objective is to investigate the optimal treatment strategies in people with early-onset T2D. Specifically, we aim to (1) compare CVD risk in GLP-1 RA and insulin users and (2) examine changes in key CVD risk factors, such as HbA1c, BMI, and lipid profiles, before and after initiation of GLP-1 RA, SGLT2 inhibitors, and insulin. Based on real-world data from Sweden we will emulate a target trial to minimize selection bias and confounding. This study will generate robust evidence to guide clinicians in optimizing treatment for early-onset T2D. Given the rising burden of this condition and the lack of specific treatment recommendations, our findings have the potential to improve long-term cardiovascular outcomes in this high-risk population.

Conditions

Type 2 Diabetes Mellitus (T2DM)

Keywords

emulated target trial; early-onset type 2 diabetes; GLP-1 RA; insulin

Outcome Measures

Primary Outcomes (1)

• MACE

  major adverse cardiovascular events (MACE), defined as a composite outcome of cardiovascular death (ICD-10 codes: I00-I99) recorded in the Causes-of-Death Register, and nonfatal myocardial infarction (ICD-10: I21, I22 in NPR), nonfatal stroke (I60-61, I63-64), and hospitalized heart failure (I50)

  2010-2021

Study Arms (4)

Early onset T2D with GLP1 RA

People with early-onset T2D and metformin who initiate GLP1-RA treatment

Drug: GLP-1

Early onset T2D with insulin

People with early-onset T2D and metformin who initiate insulin treatment

late onset T2D with GLP1 RA treatment

People with early-onset T2D and metformin who initiate GLP1-RA treatment

Drug: GLP-1

Late onset T2D with insulin

People with late-onset T2D and metformin who initiate insulin

Interventions

GLP-1 DRUG

We will compare people who have picked up GLP1 to those who have picked up insulin at any Swedish pharmacy

Early onset T2D with GLP1 RA; late onset T2D with GLP1 RA treatment

Eligibility Criteria

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

Study Population

We will apply an emulated target trial framework (Table 2 shows the specification and emulation of the target trial) based on Swedish nationwide registers to emulate a randomized clinical trial of the comparative effectiveness of GLP-1 RA and insulin on CVD incidence. Potential participants are people diagnosed with T2D at age ≥18 years in 1997-2020 (n=617,727), with at least one record in the National Diabetes Register (NDR). The date of diabetes diagnosis is defined as the first record of diabetes in NDR or the National Patient Register (NPR), or the first record of glucose-lowering drug prescription in the National Prescribed Drug Register (NPDR), or the middle of the self-reported year at diagnosis recorded in NDR, whichever comes first.

You may qualify if:

• We will include people diagnosed with T2D for more than 6 months and with metformin use within 6 months before the initiation of the treatment of interest (GLP-1 RA or insulin).

You may not qualify if:

• Individuals will be excluded if they meet one of the following criteria any time (unless stated otherwise) before or at treatment initiation: (1) other types of diabetes diagnosis recorded in NDR or NPR; (2) diagnosis of acute pancreatitis one month prior to treatment initiation; (3) diagnosis of other pancreatic diseases (chronic pancreatitis, cyst of pancreatis, etc; ICD-10 code K86) recorded in NPR; (4) use of GLP-1 RA or insulin within 1 year prior to treatment initiation, (5) advanced kidney disease (eGFR\<30 mL/min/1.73 m2, dialysis or kidney transplant \[procedure codes: KAS\[10\]\]); (6) end-stage liver disease (K70.4, K71.1, K72, Z94.4, procedure codes JJC); (7) cancer of the digestive system (ICD codes: C15-C26) or endocrine glands such as thyroid (ICD codes: C73-C75); (8) inflammatory bowel diseases (ICD-10 K50-K52)

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Karolinska Institutet, Institute of Environmental Medicine

Stockholm, 171 77, Sweden

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

Glucagon-Like Peptide 1

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Target Duration: 11 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: senior lecturer

Study Record Dates

• First Submitted: March 30, 2025
• First Posted: April 6, 2025
• Study Start: January 1, 2010
• Primary Completion: December 31, 2021
• Study Completion: January 31, 2025
• Last Updated: April 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)