Reducing cardiometabolic risk with semaglutide in type 1 diabetes (RESET1): Study protocol of a phase 2 double-blinded randomised placebo-controlled trial

Diabet Med. 2024 Oct;41(10):e15377. doi: 10.1111/dme.15377. Epub 2024 Jun 9.

Abstract

Background: Premature cardiovascular disease is the leading cause of death in people living with type 1 diabetes. Therapies are urgently needed to address cardiovascular risk in this group. Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist, has been shown to reduce cardiovascular events and improve weight and glycaemia in type 2 diabetes. Semaglutide may offer cardioprotective and metabolic benefits in type 1 diabetes.

Methods: We will study 60 adults aged 25-70 years with type 1 diabetes of duration at least 2 years, body mass index ≥25 kg/m2, HbA1c ≥7% and at least one cardiovascular risk factor (microalbuminuria, hypertension or anti-hypertensive treatment, hyperlipidemia or lipid lowering therapy, current smoking). Participants will receive semaglutide up to 1.0 mg weekly or matched placebo for 26 weeks. The primary outcome is carotid femoral pulse wave velocity, a measure of arterial stiffness, as a surrogate marker of cardiovascular risk. Potential mechanisms for metabolic changes will be explored including change in insulin sensitivity determined by hyperinsulinaemic-euglycaemic clamp; and incretin and pancreatic hormone action measured during mixed meal tolerance test.

Conclusion: The REducing cardiometabolic risk with SEmaglutide in Type 1 diabetes study will investigate whether semaglutide, a long acting glucagon-like peptide receptor agonist, can improve markers of cardiometabolic health in T1D. Underlying mechanisms predicting response, including insulin resistance and incretin hormone status, will also be explored.

Keywords: cardiometabolic risk; insulin resistance; metabolism; semaglutide; type 1 diabetes.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adult
  • Aged
  • Cardiometabolic Risk Factors
  • Cardiovascular Diseases* / prevention & control
  • Clinical Trials, Phase II as Topic
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / complications
  • Diabetes Mellitus, Type 1* / drug therapy
  • Double-Blind Method
  • Female
  • Glucagon-Like Peptides* / therapeutic use
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic

Substances

  • Glucagon-Like Peptides
  • Hypoglycemic Agents
  • semaglutide