Related Experiment Video

Updated: Jul 20, 2025

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices
06:34

Validation of Therapeutic Agent Conjugation to Polyvinyl Alcohol-Coated Medical Devices

Published on: November 29, 2024

286

GLP-1 Receptor Agonist Therapy With and Without SGLT2 Inhibitors in Patients With Type 2 Diabetes

João Sérgio Neves1, Marta Borges-Canha1, Francisco Vasques-Nóvoa2

  • 1Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal; Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Porto, Portugal.

Journal of the American College of Cardiology
|August 2, 2023
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) effectively reduce cardiovascular events in type 2 diabetes (T2D) patients, regardless of whether they also use sodium-glucose cotransporter-2 (SGLT2) inhibitors. Combination therapy may offer further risk reduction, warranting clinical trials.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors and GLP-1 receptor agonists (GLP-1 RAs) are established treatments for reducing cardiovascular events in type 2 diabetes (T2D).
  • The combined efficacy of these drug classes for cardiovascular risk reduction in T2D remains incompletely understood.

Purpose of the Study:

  • To assess the cardiovascular outcomes of GLP-1 RAs in patients with T2D, stratified by concurrent use of SGLT2 inhibitors.
  • To evaluate the potential benefits of combining GLP-1 RAs and SGLT2 inhibitors for cardiovascular risk management.

Main Methods:

  • A post hoc analysis of the Harmony Outcomes trial examined albiglutide's effect on major adverse cardiovascular events (MACE) in T2D patients with cardiovascular disease, considering baseline SGLT2 inhibitor use.
  • A trial-level meta-analysis combined data from Harmony Outcomes and AMPLITUDE-O trials to assess GLP-1 RA efficacy on MACE and heart failure hospitalizations, with and without SGLT2 inhibitor use.

Main Results:

  • In the Harmony Outcomes analysis, albiglutide consistently reduced MACE irrespective of SGLT2 inhibitor use (P interaction = 0.70).
  • The meta-analysis of 13,538 patients showed GLP-1 RAs significantly reduced MACE (HR 0.77 without SGLT2 inhibitors, HR 0.78 with SGLT2 inhibitors; P interaction = 0.95) and heart failure hospitalizations (P interaction = 0.18) independently of SGLT2 inhibitor use.
  • No significant interaction was observed between GLP-1 RA treatment effect and SGLT2 inhibitor use for major adverse cardiovascular events.

Conclusions:

  • GLP-1 RAs demonstrate efficacy in reducing cardiovascular events in T2D patients with cardiovascular disease, independent of SGLT2 inhibitor use.
  • The findings suggest that combining GLP-1 RAs and SGLT2 inhibitors may provide additive cardiovascular risk reduction.
  • Further clinical trials are recommended to confirm the benefits of combination therapy with GLP-1 RAs and SGLT2 inhibitors.
Keywords:
GLP-1 receptor agonistSGLT2 inhibitorcardiovascular diseaseheart failuretype 2 diabetes

More Related Videos

Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres09:31

Sustained Administration of β-cell Mitogens to Intact Mouse Islets Ex Vivo Using Biodegradable Poly(lactic-co-glycolic acid) Microspheres

Published on: November 5, 2016

7.3K
Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets10:09

Leprdb Mouse Model of Type 2 Diabetes: Pancreatic Islet Isolation and Live-cell 2-Photon Imaging Of Intact Islets

Published on: May 11, 2015

9.5K

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
358
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
212
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
186
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
234
Diabetes: Management and Pharmacotherapy01:15

Diabetes: Management and Pharmacotherapy

The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
313
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
208