Insulin analogs as an add-on to metformin after failure to oral treatment in type 2 diabetic patients increase diastole duration. The INSUlin Regimens and VASCular Functions (INSUVASC) study

Minerva Cardiol Angiol. 2023 Dec;71(6):659-672. doi: 10.23736/S2724-5683.23.06139-2. Epub 2023 Jul 5.

Abstract

Background: Fast acting insulin analogues are known to improve arterial stiffness. The combination of metformin with insulin represents a widely used therapeutic strategy in diabetes. We hypothesized that insulin treatment in patients with type 2 diabetes (T2D) with long-acting, fast-acting or basal bolus insulin as an add-on to metformin would provide additional improvement of arterial stiffness.

Methods: The INSUlin Regimens and VASCular Functions (INSUVASC) study is a pilot, randomized, open label three-arms study that included 42 patients with type 2 diabetes (T2D) in primary prevention, after a failure to oral antidiabetic agents. Arterial stiffness measurements were performed at fasting and after a standardized breakfast. During the first visit (V1) pre-randomization, participants took only metformin to perform the tests. The same tests were repeated after 4 weeks of insulin treatment during the second visit (V2).

Results: Data were available for final analysis in 40 patients, with a mean age of 53.6±9.7 years and a mean duration of diabetes of 10.6±5.6 years. Twenty-one were females (52.5%), hypertension and dyslipidemia were present in 18 (45%) and 17 patients (42.5%), respectively. After insulin treatment, the metabolic control was associated to a decrease in oxidative stress and improvement of endothelial functions, with a post prandial diastole duration increased and a decrease of the peripheral arterial stiffness, with a better post prandial pulse pressure ratio and ejection duration after insulin. In hypertensive patients, insulin treatment provided positive effects by decreasing the pulse wave velocity and improving reflection time.

Conclusions: A short time treatment by insulin in addition to metformin improved myocardial perfusion. Moreover, insulin treatment in hypertensive patients provides a better hemodynamic profile in large arteries.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diastole
  • Female
  • Humans
  • Insulin / adverse effects
  • Insulin / therapeutic use
  • Insulin, Regular, Human / therapeutic use
  • Male
  • Metformin* / adverse effects
  • Metformin* / therapeutic use
  • Middle Aged
  • Pulse Wave Analysis

Substances

  • Insulin
  • Metformin
  • Insulin, Regular, Human