DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature

Saini, Karanvir; Sharma, Shilpi; Khan, Yousuf Aziz

doi:10.3389/fmolb.2023.1130625

Cited by 30 publications

(15 citation statements)

References 192 publications

(234 reference statements)

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“…Also, they reduce body weight and blood pressure, showing the potential to slow the progression of diabetes and reduce the cardiovascular complications of diabetes. [8,9] Thus, incretin-based drugs have likewise received some attention for their association with PCa risk. [10] Several basic studies have shown that incretin-based drugs can inhibit the growth of prostate cancer cells in in vitro assays.…”

Section: Introductionmentioning

confidence: 99%

Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis

Lin,

Xu,

et al. 2024

Medicine

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Incretin-based drugs, a class of Antidiabetic medications (ADMs) used in the treatment of type 2 diabetes, may affect the incidence of prostate cancer (PCa). But real-world evidence for this possible effect is lacking. Therefore, the aim of this study is to assess the effect of incretin-based drugs on the incidence of PCa, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. We searched PubMed, Embase, and Cochrane Library databases for eligible studies through September 2023. Two independent reviewers performed screening and data extraction. We used the Cochrane Handbook for Systematic Reviews and the Newcastle-Ottawa Scale (NOS) to assess the quality of included randomized controlled trials (RCTs) and cohort studies. We did a meta-analysis of available trial data to calculate overall risk ratios (RRs) for PCa. A total of 1238 articles were identified in our search. After screening for eligibility, 7 high-quality studies met the criteria for meta-analysis, including 2 RCTs and 5 cohort studies, with a total of 1165,738 patients. Compared with the control group, we found that incretin-based drugs reduced the relative risk of PCa by 35% (95% confidence interval (CI), 0.17–0.49; P = .0006). In subgroup analysis, the RR values for GLP-1 receptor agonists and DPP-4 inhibitors were 62% (95% CI, 0.45–0.85; P = .003) and 72% (95% CI, 0.46–1.12; P = .14), respectively. Incretin-based drugs are associated with lower incidence of prostate cancer and may have a preventive effect on prostate cancer in patients with type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis

Lin,

Xu,

et al. 2024

Medicine

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“…Notably, the concept of tight-binding inhibitors emerges as pivotal in the pharmacological context. The ability of these inhibitors to tightly bind to their target ensures a sustained inhibition of enzyme activity, 9 which results in persistent diurnal effects on glucose, β cells and incretin hormones without significant differences between them. 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anti-Diabetic Activity of an 8-Purine Derivative as a Novel DPP-4 Inhibitor in Obese Diabetic Zücker Rats

Chayah,

Luque-González,

Gómez-Pérez

et al. 2024

DDDT

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Type 2 diabetes mellitus (T2DM) is one of the world’s principal metabolic diseases characterized by chronic hyperglycemia. The gut incretin hormones, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), which has been proposed as a new treatment for T2DM, are extensively metabolized by Dipeptidyl peptidase 4 (DPP-4). Inhibitors of DPP-4 block the degradation of GLP-1 and GIP and may increase their natural circulating levels, favoring glycemic control in T2DM. A novel and potent selective inhibitor of DPP-4 with an 8-purine derived structure ( 1 ) has been developed and tested in vitro and in vivo in Zücker obese diabetic fatty (ZDF) rats, an experimental model of the metabolic syndrome and T2DM to assess the inhibitory activity using vildagliptin as reference standard. ZDF rats were subdivided into three groups (n = 7/group), control (C-ZDF), and those treated with compound 1 (Compound 1 -ZDF) and with vildagliptin (V-ZDF), both at 10 mg/kg/d rat body weight, in their drinking water for 12 weeks, and a group of lean littermates (ZL) was used. ZDF rats developed DM (fasting hyperglycemia, 425 ± 14.8 mg/dL; chronic hyperglycemia, HbA1c 8.5 ± 0.4%), compared to ZL rats. Compound 1 and vildagliptin reduced sustained HbAl1c (14% and 10.6%, P < 0.05, respectively) and fasting hyperglycemia values (24% and 19%, P < 0.05, respectively) compared to C-ZDF group (P < 0.001). Compound 1 and vildagliptin have shown a potent activity with an IC 50 value of 4.92 and 3.21 µM, respectively. These data demonstrate that oral compound 1 administration improves diabetes in ZDF rats by the inhibitory effect on DPP-4, and the potential to be a novel, efficient and tolerable approach for treating diabetes of obesity-related T2DM, in ZDF rats.

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“…They also have other beneficial effects on glucose metabolism, lipid metabolism, appetite regulation, gut motility, and immune function. They also have anti-inflammatory properties that reduce cardiovascular risk, help preserve beta-cell function, and improve renal function [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…Some of the common side effects of DPP-4 inhibitors are upper respiratory tract infections, urinary tract infections, headaches, and nasopharyngitis. Moreover, this class of drugs has been associated with rare but serious complications, such as pancreatitis, pancreatic cancer, thyroid cancer, and sometimes severe allergic reactions [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Dermatological side effects of dipeptidyl Peptidase-4 inhibitors in diabetes management: a comprehensive review

Zaresharifi,

Niroomand,

Borran

et al. 2024

Clin Diabetes Endocrinol

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Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of drugs that enhance the incretin-insulin pathway and offer effective glycemic control in type 2 diabetes mellitus. However, these drugs may be associated with various dermatological side effects, ranging from mild to severe. This review article summarizes the current literature on the dermatological side effects of DPP-4 inhibitors, including bullous pemphigoid, severe cutaneous adverse drug reactions, fixed drug eruptions, and other mucocutaneous reactions. The review also discusses the possible mechanisms, risk factors, diagnosis, and management of these side effects. This review aims to increase the awareness and vigilance of healthcare providers in recognizing and managing the dermatological side effects of DPP-4 inhibitors and to emphasize the need for further research and surveillance to optimize diabetes care and patient safety.

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DPP-4 inhibitors for treating T2DM - hype or hope? an analysis based on the current literature

Cited by 30 publications

References 192 publications

Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis

Incretin-based drugs decrease the incidence of prostate cancer in type 2 diabetics: A pooling-up analysis

Synthesis and Anti-Diabetic Activity of an 8-Purine Derivative as a Novel DPP-4 Inhibitor in Obese Diabetic Zücker Rats

Dermatological side effects of dipeptidyl Peptidase-4 inhibitors in diabetes management: a comprehensive review

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