The Old and the New in the Treatment of Type 2 Diabetes: Focus on the Combination Therapy with Dipeptidyl Peptidase-4 Inhibitors and Metformin

2010 ◽  
Vol 2 ◽  
pp. CMT.S3420 ◽  
Author(s):  
Giovanni Anfossi ◽  
Isabella Russo ◽  
Katia Bonomo ◽  
Mariella Trovati
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Microvascular Complications ◽  
Chronic Complications ◽  
Dipeptidyl Peptidase 4 ◽  
Chronic Hyperglycemia ◽  
Oral Agents ◽  
Dipeptidyl Peptidase 4 Inhibitors

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease which affects the length and quality of life by severe chronic complications. Chronic hyperglycemia, which is the main alteration in T2DM, is strictly related to microvascular complications (such as retinopathy and nephropathy) and neuropathy, whereas large vessel atherosclerosis is also dependent on lipid and hemostasis abnormalities, arterial hypertension and other known cardiovascular risk factors. An early intervention to control hyperglycemia and to prevent deterioration of β-cell function is considered mandatory in patients with T2DM to minimize the risk of chronic complications. Recently, the availability of new pharmacological agents with different targets, including the activation of the incretin system has allowed the proposal of more effective strategies for early treatment of metabolic alterations in patients with T2DM. This commentary will focus on the role of new oral agents influencing the incretin system and the putative advantages of their co-administration with metformin, an old, effective anti-hyperglycemic agent also able to exert beneficial actions on arterial vessels, reducing the risk of macrovascular-related events. The vasoprotective role of metformin is largely independent of its hypoglycemic action, and has been ascribed to pleiotropic effects.

Switching from Premixed Insulin To Basal Insulin Analogue For Type 2 Diabetes and Role of Dipeptidyl Peptidase-4 Inhibitors

2017 ◽  
Vol 126 (05) ◽  
pp. 268-276 ◽  
Author(s):  
Fernando Gómez-Peralta ◽  
Cristina Abreu ◽  
Gustavo Mora-Navarro ◽  
Pilar López-Morandeira ◽  
Esteban Pérez-Gutierrez ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Basal Insulin ◽  
Insulin Analogue ◽  
Dipeptidyl Peptidase ◽  
Premixed Insulin ◽  
Dipeptidyl Peptidase 4 ◽  
Metformin Group ◽  
Dipeptidyl Peptidase 4 Inhibitors

Abstract Introduction This study aimed to confirm the usefulness of basal insulin analogue plus oral antidiabetic drugs (OADs) for type 2 diabetes (T2D) patients inadequately controlled with premixed insulin with/without OADs and assess the role of dipeptidyl peptidase-4 (DPP-4) inhibitors within this regimen in clinical practice. Methods Spanish retrospective observational study that included 186 T2D patients with glycosylated hemoglobin (HbA1c) >7% (53 mmol/mol) despite premixed insulin with/without OADs who had been switched to basal insulin analogue plus OADs. Study data describing the situation before the treatment switch and 6 months later was retrospectively retrieved from patients’ medical charts. Results Switching to a basal insulin plus OADs decreased HbA1c (−1.0%, p<0.001), fasting (−38.1 mg/dl, p<0.001) and postprandial glycemia (−36.1 mg/dl, p<0.001), with reduced body weight (−1.1 kg, p<0.001) and hypoglycemic episodes (−17.5%, p<0.001). 68 (36.6%) patients received a basal insulin plus DPP-4 inhibitor±metformin and 74 (39.8%) plus metformin only. The DPP-4 inhibitor±metformin group showed a greater HbA1c reduction than the metformin group (1.3±1.4% vs. 0.9±1.0%, p=0.022), with no significant differences between groups in hypoglycemic episodes. Conclusions Basal insulin analogue plus OADs may be a useful treatment for type 2 diabetes patients inadequately controlled with premixed insulin. Administering DPP-4 inhibitors within this regimen may contribute to improve patients’ glycemia, with a favorable weight-change profile and without increasing hypoglycemia risk.

scholarly journals Therapeutic Role of Dipeptidyl Peptidase-4 Inhibitors in COVID-19

2020 ◽  
pp. 1-4
Author(s):  
Nasser Mikhail ◽  
◽  
Soma Wali ◽  
Keyword(s):  
Type 2 Diabetes ◽  
Retrospective Studies ◽  
Clinical Status ◽  
Dipeptidyl Peptidase ◽  
Therapeutic Role ◽  
Dipeptidyl Peptidase 4 ◽  
Beneficial Effects ◽  
Dipeptidyl Peptidase 4 Inhibitors

Background: Limited retrospective data suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin may decrease mortality in patients with type 2 diabetes hospitalized with coronavirus disease 2019 (COVID-19). Objective: To review the strength of evidence that supports possible therapeutic role of DPP-4 inhibitors in COVID-19. Methods: PUBMED search until October 10, 2020. Search terms included COVID-19, DPP-4 inhibitors, sitagliptin, CD26, mortality, diabetes. Retrospective studies, pertinent animal investigations and pre-print studies are reviewed. Results: Three retrospective studies have shown that use of DPP-4 inhibitors was associated with significant mortality reduction of approximately 56- 87% in patients with diabetes admitted with COVID-19. In addition, in one of these studies, the use of sitagliptin before hospitalization was associated with greater number of hospital discharges, improvement of clinical status, reduced risk of transfer to intensive care unit (ICU) and need for mechanical ventilation compared with patients who were not receiving sitagliptin. Moreover, there was significant decrease in some pro-inflammatory markers in the sitagliptin group. A small retrospective study of 9 patients who were taking a DPP-4 inhibitor prior to admission did not find any significant effect of DPP-4 inhibitors on mortality and clinical outcomes after hospitalization. Results of another small study suggested increase susceptibility to COVID-19, but not to its severity, in patients taking DPP-4 inhibitors. Conclusions: Weak evidence derived from observational studies suggests possible beneficial effects of DPP-4 inhibitors use in patients with type 2 diabetes and COVID-19. Randomized trials are urgently needed to clarify the efficacy and safety of DPP-4 inhibitors in patients with COVID-19 with and without type 2 diabetes

scholarly journals An Emerging Role of Glucagon-Like Peptide-1 in Preventing Advanced-Glycation-End-Product-Mediated Damages in Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Alessandra Puddu ◽  
François Mach ◽  
Alessio Nencioni ◽  
Giorgio Luciano Viviani ◽  
Fabrizio Montecucco
Keyword(s):  
Type 2 Diabetes ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Advanced Glycation ◽  
Chronic Hyperglycemia ◽  
Gut Hormone ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1 (GLP-1) is a gut hormone produced in the intestinal epithelial endocrine L cells by differential processing of the proglucagon gene. Released in response to the nutrient ingestion, GLP-1 plays an important role in maintaining glucose homeostasis. GLP-1 has been shown to regulate blood glucose levels by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion, gastric emptying, and food intake. These antidiabetic activities highlight GLP-1 as a potential therapeutic molecule in the clinical management of type 2 diabetes, (a disease characterized by progressive decline of beta-cell function and mass, increased insulin resistance, and final hyperglycemia). Since chronic hyperglycemia contributed to the acceleration of the formation of Advanced Glycation End-Products (AGEs, a heterogeneous group of compounds derived from the nonenzymatic reaction of reducing sugars with free amino groups of proteins implicated in vascular diabetic complications), the administration of GLP-1 might directly counteract diabetes pathophysiological processes (such as pancreaticβ-cell dysfunction). This paper outlines evidence on the protective role of GLP-1 in preventing the deleterious effects mediated by AGEs in type 2 diabetes.

scholarly journals Fixed-Dose Combination of Dipeptidyl Peptidase-4 Inhibitors Plus Metformin in Patients with Type 2 Diabetes: A Review on Safety and Efficacy

2021 ◽  
pp. 53-59
Author(s):  
Sultan M. Alshahrani ◽  
Hamed Ali Alshahrani ◽  
Saud Dhafer Alshahrani ◽  
Noura Mohammed Alabdulla ◽  
Yazeed Fahad Alshahrani ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
International Diabetes Federation ◽  
Dipeptidyl Peptidase ◽  
Fixed Dose ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Oral Agents ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Fixed Drug

There is a significant increase noted in the incidence and prevalence of Type 2 diabetes mellitus (T2DM). The global number of diabetic patients is projected by the International Diabetes Federation (IDF) to reach 552 million. T2DM disease has chronic and progressive nature. More than fifty percent of patients do not attain adequate glycemic control despite initial sufficient monotherapy. To maintain target glycated hemoglobin (HbA1c) levels (<7%), dose adjustment and adoption of several diabetes therapies become necessary in many cases. Compared to monotherapy, a fixed drug combination of oral agents and metformin has proven to be more efficacious to maintain levels of blood glucose and HbA1c. The combination of dipeptidyl peptidase-4 inhibitors (DDPIs) and metformin has been explicated to effectively decrease HbA1c to a relatively higher degree compared to the use of either agent individually. This combination addresses various pathophysiological processes involved in T2DM pathogenesis. Additionally, the concerned combination is safe and associated with a lower risk of hypoglycemia. Moreover, it is well-tolerated and prescribed as an easy-to-use single pill to improve patient compliance. This review provides an overview of the pharmacology, efficacy, and safety of fixed drug combinations of DDPIs and metformin according to current practice.

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