DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits

Razavi, Michael; Wei, Yingying; Rao, Xiaoquan; Zhong, Jixin

doi:10.1186/s40779-022-00410-2

Cited by 16 publications

(19 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TZDs (pioglitazone is the most commonly used) are beta-cell-protective and potent insulin sensitizers that exert effects on muscle, liver, and fat cells [28]. GLP-1RAs directly increase insulin secretion through beta-cell-protective functions and suppress glucagon secretions by inhibiting alpha cells and increasing insulin sensitivity [56]. Indirectly, they also cause slowed gastric emptying and weight loss and induce favorable lipid profiles [57].…”

Section: Ideal Combinationmentioning

confidence: 99%

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Gudoor,

Suits,

Shubrook

2023

Diabetology

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is a debilitating, lifelong condition with a rising incidence. A wide variety of antihyperglycemic agents are available on the market to treat diabetes. However, the number of patients living with diabetes under suboptimal control remains relatively high. This calls into question whether the application of the current treatment standards is effective and durable to truly manage the disease well. This paper aims to highlight the various classes of antihyperglycemic agents from a pathophysiologic perspective and explore the best possible combination that can have a durable effect on diabetes management. To determine this, an eight-piece pathophysiologic puzzle was created, each piece representing an organ system affected by the disease—liver, pancreas (alpha and beta cells), muscle, adipose tissue, gut, brain, and kidneys. Choosing a combination therapy that is both durable and can effectively address all eight pieces of the puzzle can theoretically create sustainable ameliorating effects. This combination can potentially lead to reduced microvascular and macrovascular complications, as well as work towards creating an ideal long-term, affordable diabetes care plan.

show abstract

Section: Ideal Combinationmentioning

confidence: 99%

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Gudoor,

Suits,

Shubrook

2023

Diabetology

View full text Add to dashboard Cite

show abstract

“…Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are a class of novel oral antidiabetic medications. They stimulate β‐cell growth, proliferation, and differentiation, and promote β‐cell secretion by reducing entero‐insulin inactivation, increasing the levels of endogenous GLP‐1 and glucose‐dependent insulinotropic peptide, and prolonging the action of insulin, thereby lowering blood glucose 60 . Additionally, DPP‐4 inhibitors inhibit the degradation of Stromal cell‐derived factor‐1α and enhance the homing of endothelial progenitor cells, which eventually exert vasoprotective effects 62 .…”

Section: Recent Advances In Treatment Researchmentioning

confidence: 99%

“…59 The most common side effects of GLP-1 RAs are gastrointestinal reactions. 60,61 Among them, semaglutide carries the highest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide carries the highest risk of upper abdominal pain. 61 cell-derived factor-1α and enhance the homing of endothelial progenitor cells, which eventually exert vasoprotective effects.…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 99%

Progress in the treatment of diabetic cardiomyopathy, a systematic review

Shou,

Li,

Fang

et al. 2024

Pharmacology Res & Perspec

View full text Add to dashboard Cite

Diabetic cardiomyopathy (DCM) is a condition characterized by myocardial dysfunction that occurs in individuals with diabetes, in the absence of coronary artery disease, valve disease, and other conventional cardiovascular risk factors such as hypertension and dyslipidemia. It is considered a significant and consequential complication of diabetes in the field of cardiovascular medicine. The primary pathological manifestations include myocardial hypertrophy, myocardial fibrosis, and impaired ventricular function, which can lead to widespread myocardial necrosis. Ultimately, this can progress to the development of heart failure, arrhythmias, and cardiogenic shock, with severe cases even resulting in sudden cardiac death. Despite several decades of both fundamental and clinical research conducted globally, there are currently no specific targeted therapies available for DCM in clinical practice, and the incidence and mortality rates of heart failure remain persistently high. Thus, this article provides an overview of the current treatment modalities and novel techniques pertaining to DCM, aiming to offer valuable insights and support to researchers dedicated to investigating this complex condition.

show abstract

“…While SU are a clear representation of diabetes precision medicine, they are non-efficacious in some individuals and their efficacy may not be durable in others, with diabetes duration and weight gain being two factors associated with reduced SU efficacy. The increased cardiovascular risk associated with HNF1A-diabetes provides another reason that carefully-designed, long-term comparison studies of glycemic and cardiovascular outcomes of these newer classes of diabetes medications, which offer cardiovascular benefit, are needed 123,124 .…”

Section: Hnf1a-diabetes and Hnf4a-diabetesmentioning

confidence: 99%

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Naylor

Patel

Kettunen

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for a precision medicine approach. We systematically reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-diabetes, HNF4A-diabetes, HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes (Thiamine-Responsive Megaloblastic Anemia, TRMA). Methods: Systematic review with data sources from PubMed, MEDLINE and Embase were performed answering specific therapeutic questions for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes. Results: 147 studies met inclusion criteria with only six experimental studies (four randomized trials for HNF1A-diabetes) and the rest being single case reports or cohort studies. Most studies were rated as having moderate or serious risk of bias. For GCK-related hyperglycemia, six studies (35 individuals) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited to three studies (16 individuals) showing lower HbA1c with SU therapy. The 13 studies in HNF1B-diabetes (n=301) and 10 in MD with m.3243A>G variant (n=250) showed that while some patients can be treated with oral agents the majority of patients were insulin treated. In HNF1B-diabetes the attempts to transfer from insulin to oral hypoglycemic agents (OHA) were unsuccessful in most cases. In 6q24-TND there were insufficient studies supporting OHA close to diagnosis before remission but more support for their use after relapse. In SLC19A2-diabetes there was some evidence that treatment with thiamine improved glycemic control and reduced insulin requirement while less than half achieved insulin-independency. Conclusion: There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The combined data does support: no treatment being needed in GCK-related hyperglycemia; SU being used as the first line treatment in HNF1A-diabetes; SU can be tried in HNF4A-diabetes; insulin often needed in HNF1B-diabetes and MD with the m.3243A>G variant; SU can be tried in 6q24-TND relapse; and thiamine may improve glycemic control in SLC19A2-diabetes. Further evidence, particularly randomized comparative studies, are needed to examine the optimum treatment for glycemic response in all monogenic subtypes.

show abstract

DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits

Cited by 16 publications

References 99 publications

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Progress in the treatment of diabetic cardiomyopathy, a systematic review

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Contact Info

Product

Resources

About