Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults
Condition: Coronary Microvascular Dysfunction
Study type: Interventional
Phase: Phase 4

Summary: 
      GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the
      cardiovascular system. The mechanism is complex and there seems to be a dual function with
      intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite
      acting independently of the GLP-1 receptor.

      Coronary flow reserve (CFR) is the ratio of flow through the coronary arteries during stress
      to during rest and it reflects coronary microcirculation. Impaired CFR is a strong predictor
      of poor prognosis of cardiovascular disease.

      The aim of the study is to investigate the acute effects of GLP-1 on coronary
      microcirculation and endothelial function in adults with obesity.
    

Detailed description: 
      Several studies have shown beneficial effects of glucagon-like-peptide-1 (GLP-1) on the
      cardiovascular system. Native GLP-1 is secreted from L-cells in the intestine as GLP-1(7-36)
      1 but is rapidly metabolised by the ubiquitous enzyme dipeptidyl-peptidase-4 (DPP4) to the
      metabolite GLP-1(9-36). However, the physiological effect of GLP-1 on the cardiovascular
      system is complex and there seems to be a dual function with intact GLP-1 (7-36), acting
      through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1
      receptor.

      The aim of the study is to investigate the acute effects of intact GLP-1 and GLP-1 metabolite
      on coronary microcirculation and endothelial function in adults.

      Method 20 adults with obesity are recruited to a double-blind randomized cross-over study.

      The first 10 included adults will receive 2½ hours infusion of intact GLP-1 (7-36) together
      with a DPP-IV inhibitor and 2½ hours infusion of saline, on two separate occasions. The
      infusions will be given in randomized order with a minimum of 24 hours washout period.

      The next 10 included adults will receive 2½ hours infusion of GLP-1 (9-36) metabolite and 2½
      hours infusion of saline. These will also be given in randomized order with a minimum of 24
      hours washout period. Endothelial function and CFR will be measured before and after one,
      respectively two, hours of infusion.

      The effect of GLP-1 infusions on microvascular function is evaluated by coronary flow reserve
      (CFR), the ratio between echocardiographic measured coronary flow velocity in LAD during
      adenosine induced myocardial hyperaemia and rest. The effect on endothelial function is
      assessed by flow mediated dilation (FMD).
    

Intervention name(s): GlucagonLikePeptide-1 (7-36); GlucagonLikePeptide-1 (9-36); Saline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.; Diluted in saline and human serum albumin, then infused intravenously for 2,5 hours.; Infused intravenously for 2,5 hours.
Other intervention name(s): NaCl, Placebo
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science