Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control

Kang, Seon Mee; Park, Jeong Hyun

doi:10.1177/11795514211051698

Cited by 16 publications

(16 citation statements)

References 121 publications

(141 reference statements)

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“…Since the cure is nearly impossible for DM treatment in the current time, the DM control needs lifelong struggle and treatment. 112,113 The prescription of ADA should be according to the patient’s age, patient’s compliance, patient’s general condition, disease course, drug efficacy, and drug-related side effects. 10,44 Therefore, the development of new T2DM drugs with better efficacy, fewer side effects and potential repositioning for any new indications or concomitant benefits for health promotion is a problem that researchers have been actively addressing.…”

Section: Prevention and Management Of Osteoporosis In T2dm: Modificat...mentioning

confidence: 99%

To do one and to get more: Part I. Diabetes and bone

Lee

Wang

Yang

et al. 2022

Journal of the Chinese Medical Association

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Type 2 diabetes mellitus (T2DM), is a chronic metabolic disease, characterized by the presence of hyperglycemia and insulin resistance. The key treatment strategies for T2DM include modification of lifestyle, medications, and continuous glucose monitoring. DM patients often have DM-associated morbidities and comorbidities; however, disorders of musculoskeletal system are often neglected, compared to other major systems in DM patients. Based on sharing similar pathophysiology of DM and osteoporosis, it is supposed that the use of antidiabetic agents (ADAs) may not only provide the lowering glucose level effect and the maintenance of the sugar homeostasis to directly delay the tissue damage secondary to hyperglycemia but also offer the benefits, such as the prevention of developing osteoporosis and fractures. Based on the current review, evidence shows the positive correlation between DM and osteoporosis or fracture, but the effectiveness of using ADA in the prevention of osteoporosis and subsequent reduction of fracture seems to be inconclusive. Although the benefits of ADA on bone health are uncertain, the potential value of "To do one and to get more" therapeutic strategy should be always persuaded. At least, one of the key treatment strategies as an establishment of healthy lifestyle may work, because it improves the status of insulin resistance and subsequently helps DM control, prevents the DM-related micro-and macrovascular injury, and possibly strengthens the general performance of musculoskeletal system. With stronger musculoskeletal system support, the risk of "fall" may be decreased, because it is associated with fracture. Although the ADA available in the market does not satisfy the policy of "To do one and to get more" yet, we are looking forward to seeing the continuously advanced technology of drug development on diabetic control, and hope to see their extra-sugar-lowering effects.

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Section: Prevention and Management Of Osteoporosis In T2dm: Modificat...mentioning

confidence: 99%

To do one and to get more: Part I. Diabetes and bone

Lee

Wang

Yang

et al. 2022

Journal of the Chinese Medical Association

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“…Dipeptidyl peptidase-4 (DPP-4) inhibitors are antihyperglycemic drugs used as second-line to third-line treatment in type 2 diabetes 1 2. With their rising use, previously unanticipated beneficial as well as adverse effects, including a potential association with skin cancer,3 have emerged 4…”

Section: Introductionmentioning

confidence: 99%

“…1 2 With their rising use, previously unanticipated beneficial as well as adverse effects, including a potential association with skin cancer, 3 have emerged. 4 Skin cancer, including melanoma and nonmelanoma skin cancer, represents the the most common human malignancy. 5 Despite recent progress, 6 melanoma entails a poor prognosis, 7 while non-melanoma skin cancer disproportionately impacts the underpriviledged, [8][9][10] highlighting the continued need for cost-effective preventive and therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study

Pradhan,

Yu,

Platt

et al. 2023

BMJ Open Diab Res Care

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IntroductionThe dipeptidyl peptidase-4 (DPP-4) enzyme significantly influences carcinogenic pathways in the skin. The objective of this study was to determine whether DPP-4 inhibitors are associated with the incidence of melanoma and nonmelanoma skin cancer, compared with sulfonylureas.Research design and methodsUsing the United Kingdom Clinical Practice Research Datalink, we assembled two new-user active comparator cohorts for each skin cancer outcome from 2007 to 2019. For melanoma, the cohort included 96 739 DPP-4 inhibitor users and 209 341 sulfonylurea users, and 96 411 DPP-4 inhibitor users and 208 626 sulfonylurea users for non-melanoma skin cancer. Propensity score fine stratification weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs of melanoma and non-melanoma skin cancer, separately.ResultsOverall, DPP-4 inhibitors were associated with a 23% decreased risk of melanoma compared with sulfonylureas (49.7 vs 65.3 per 100 000 person-years, respectively; HR 0.77, 95% CI 0.61 to 0.96). The HR progressively reduced with increasing cumulative duration of use (0–2 years HR 1.14, 95% CI 0.84 to 1.54; 2.1–5 years HR 0.44, 95% CI 0.29 to 0.66; >5 years HR 0.33, 95% CI 0.14 to 0.74). In contrast, these drugs were not associated with the incidence of non-melanoma skin cancer, compared with sulfonylureas (448.1 vs 426.1 per 100 000 person-years, respectively; HR 1.06, 95% CI 0.98 to 1.15).ConclusionsIn this large, population-based cohort study, DPP-4 inhibitors were associated with a reduced risk of melanoma but not non-melanoma skin cancer, compared with sulfonylureas.

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“…Carbohydrate absorption from the small intestine is inhibited by α-amylase and α-glucosidase inhibitors like acarbose, miglitol, and Voglibose, as they block enzymes that transform complex non-absorbable polysaccharides into simple absorbable carbohydrates by competing with them and delaying their absorption, thereby helping in managing postprandial hyperglycemia [6]. Another strategy is to reduce the action of the ubiquitous enzyme DPP-4 by using oral anti-diabetic medicines such DPP-4 inhibitors like sitagliptin, vildagliptin, which boost the activity of incretins from the intestine [7]. Delaying the degradation of incretin hormones enhances insulin secretion and glycogenesis by promoting α and β cell functions, consequently suppressing the PPHG [8].…”

Section: Introductionmentioning

confidence: 99%

Bioactivity Guided Study for the Isolation and Identification of Antidiabetic Compounds from Edible Seaweed—Ulva reticulata

et al. 2022

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Managing diabetes is challenging due to the complex physiology of the disease and the numerous complications associated with it. As part of the ongoing search for antidiabetic chemicals, marine algae have been demonstrated to be an excellent source due to their medicinal properties. In this study, Ulva reticulata extracts were investigated for their anti-diabetic effect by examining its inhibitory effects on α-amylase, α-glucosidase, and DPP-IV and antioxidant (DPPH) potential in vitro and its purified fraction using animal models. Among the various solvents used, the Methanolic extract of Ulva reticulata (MEUR) displayed the highest antidiabetic activity in both in vitro and in vivo; it showed no cytotoxicity and hence was subjected to bioassay-guided chromatographic separation. Among the seven isolated fractions (F1 to F7), the F4 (chloroform) fraction exhibited substantial total phenolic content (65.19 μg mL−1) and total flavonoid content (20.33 μg mL−1), which showed the promising inhibition against α-amylase (71.67%) and α-glucosidase (38.01%). Active fraction (F4) was further purified using column chromatography, subjected to thin-layer chromatography (TLC), and characterized by spectroscopy techniques. Upon structural elucidation, five distinct compounds, namely, Nonane, Hexadecanoic acid, 1-dodecanol, Cyclodecane methyl, and phenol, phenol (3,5-bis(1,1-dimethylethyl) were identified. The antidiabetic mechanism of active fraction (F4) was further investigated using various in vitro and in vivo models. The results displayed that in in vitro both 1 and 24 h in vitro cultures, the active fraction (F4) at a concentration of 100 μg mL−1 demonstrated maximum glucose-induced insulin secretion at 4 mM (0.357 and 0.582 μg mL−1) and 20 mM (0.848 and 1.032 μg mL−1). The active fraction (F4) reduces blood glucose levels in normoglycaemic animals and produces effects similar to that of standard acarbose. Active fraction (F4) also demonstrated outstanding hypoglycaemic activity in hyperglycemic animals at a dose of 10 mg/kg B.wt. In the STZ-induced diabetic rat model, the active fraction (F4) showed a (61%) reduction in blood glucose level when compared to the standard drug glibenclamide (68%). The results indicate that the marine algae Ulva reticulata is a promising candidate for managing diabetes by inhibiting carbohydrate metabolizing enzymes and promoting insulin secretion.

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Pleiotropic Benefits of DPP-4 Inhibitors Beyond Glycemic Control

Cited by 16 publications

References 121 publications

To do one and to get more: Part I. Diabetes and bone

To do one and to get more: Part I. Diabetes and bone

Dipeptidyl peptidase-4 inhibitors and the risk of skin cancer among patients with type 2 diabetes: a UK population-based cohort study

Bioactivity Guided Study for the Isolation and Identification of Antidiabetic Compounds from Edible Seaweed—Ulva reticulata

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