SGLT2i increased the plasma fasting glucagon level in patients with diabetes: A meta-analysis

Zhu, Xiaoxi; Lin, Chu; Li, Li; Hu, Suiyuan; Cai, Xiaoling

doi:10.1016/j.ejphar.2021.174145

Cited by 5 publications

(6 citation statements)

References 51 publications

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“…Interestingly, a reduction in triglyceride concentrations are reported in humans treated with SGLT2i (Heymsfield et al, 2020; Pradhan et al, 2019); however, circulating ketone concentrations are increased, presumably due to a decrease in blood glucose concentrations (Ferrannini et al, 2017; Qiu et al, 2017). Given that ketogenic pathways are relatively unimportant in horses (Rose & Sampson, 1982), the authors' hypothesise that triglycerides are increased in response to lowered blood glucose and insulin concentrations, increased glucagon secretion and subsequent lipolysis (Janež & Fioretto, 2021; Sargent, 2015; Zhu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

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Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

Sundra¹,

Kelty

Rendle³

2022

Equine Veterinary Education

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Background: Hyperinsulinaemia-associated laminitis (HAL) is encountered commonly in equine practice. There are currently no registered medications which specifically target hyperinsulinaemia in horses and ponies. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to limit post-prandial insulin responses and prevent the development of diet-induced laminitis. Objectives:The objective of the study was to evaluate the efficacy of an SGLT2i, ertugliflozin, in the management of hyperinsulinaemia and laminitis. Study design: Retrospective case series.Methods: Medical records of 51 horses and ponies that had presented with laminitis and hyperinsulinaemia and had been treated with oral ertugliflozin at 0.05 mg/kg once daily for a minimum of 30 days were reviewed.Results: After 30 days of treatment with ertugliflozin, there was a reduction in insulin concentrations from a median of >300 μu/ml (IQR: 149, >300) to 43 μu/ml (IQR: 20, 66) (p < 0.001). Modified Obel laminitis scores improved, reducing from a median of 10/12 to 1/12 (p < 0.001). Median serum triglyceride concentrations increased from 0.6 (IQR: 0.4, 0.9) before treatment to 1.4 (IQR: 0.8, 3.7) mmol/L after 30 days of treatment (p < 0.001) before declining, however, none of the horses developed any clinical signs of hyperlipaemia. Ten horses (19%) were reported to have polyuria and polydipsia during treatment, otherwise no adverse clinical effects were identified. Main limitations:The study was limited by the absence of a control group, the retrospective data collection and the short period of follow-up.Conclusions: Ertugliflozin may be effective in reducing insulin concentrations in horses and ponies with equine metabolic syndrome and its use may hasten recovery from laminitis associated with hyperinsulinaemia.

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Section: Discussionmentioning

confidence: 99%

“…Given that ketogenic pathways are relatively unimportant in horses (Rose & Sampson, 1982), the authors' hypothesise that triglycerides are increased in response to lowered blood glucose and insulin concentrations, increased glucagon secretion and subsequent lipolysis (Janež & Fioretto, 2021;Sargent, 2015;Zhu et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

Sundra¹,

Kelty

Rendle³

2022

Equine Veterinary Education

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“…Although the first interest in SGLT2i was their glucose-lowering capacity, lately there have been described pleiotropic effects of SGLT2i in a wide range of targets throughout the body ( Figure 2 ). Using different experimental approaches and in different scenarios, SGLT2i have been shown to participate in the regulation of osmotic natriuresis and diuresis [ 103 , 104 ], hypertension [ 105 ], glucagon [ 106 , 107 ] and energy metabolism [ 108 , 109 , 110 , 111 , 112 ], mitochondrial function and biogenesis [ 113 , 114 , 115 , 116 , 117 , 118 ], autophagy [ 112 , 119 , 120 , 121 , 122 , 123 , 124 , 125 ], oxidative stress [ 46 , 123 , 126 , 127 , 128 , 129 ], fibrosis [ 46 , 130 , 131 , 132 , 133 ], apoptosis [ 122 , 128 , 134 , 135 , 136 , 137 , 138 , 139 ], endoplasmic reticulum stress [ 124 , 139 , 140 , 141 , 142 , 143 ], or inflammation [ 120 ,…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models

Feijóo‐Bandín

Aragón-Herrera

Otero-Santiago

et al. 2022

IJMS

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Sodium-glucose co-transporter 2 inhibitors, also known as gliflozins, were developed as a novel class of anti-diabetic agents that promote glycosuria through the prevention of glucose reabsorption in the proximal tubule by sodium-glucose co-transporter 2. Beyond the regulation of glucose homeostasis, they resulted as being effective in different clinical trials in patients with heart failure, showing a strong cardio-renal protective effect in diabetic, but also in non-diabetic patients, which highlights the possible existence of other mechanisms through which gliflozins could be exerting their action. So far, different gliflozins have been approved for their therapeutic use in T2DM, heart failure, and diabetic kidney disease in different countries, all of them being diseases that have in common a deregulation of the inflammatory process associated with the pathology, which perpetuates and worsens the disease. This inflammatory deregulation has been observed in many other diseases, which led the scientific community to have a growing interest in the understanding of the biological processes that lead to or control inflammation deregulation in order to be able to identify potential therapeutic targets that could revert this situation and contribute to the amelioration of the disease. In this line, recent studies showed that gliflozins also act as an anti-inflammatory drug, and have been proposed as a useful strategy to treat other diseases linked to inflammation in addition to cardio-renal diseases, such as diabetes, obesity, atherosclerosis, or non-alcoholic fatty liver disease. In this work, we will review recent studies regarding the role of the main sodium-glucose co-transporter 2 inhibitors in the control of inflammation.

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“…Plasma glucagon levels increased in all subjects. This is a well-described effect of SGLT2i therapy and may suggest reduced beta-cell insulin secretion [ 47 ]. Supporting this notion, there was also a borderline increase in pancreatic polypeptide levels though C-peptide concentrations did not change.…”

Section: Discussionmentioning

confidence: 99%

Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study

et al. 2023

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Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Thus, there is an urgent need for safe and effective novel therapies. PDAC’s excessive reliance on glucose metabolism for its metabolic needs provides a target for metabolic therapy. Preclinical PDAC models have demonstrated that targeting the sodium-glucose co-transporter-2 (SGLT2) with dapagliflozin may be a novel strategy. Whether dapagliflozin is safe and efficacious in humans with PDAC is unclear. Methods We performed a phase 1b observational study (ClinicalTrials.gov ID NCT04542291; registered 09/09/2020) to test the safety and tolerability of dapagliflozin (5 mg p.o./day × 2 weeks escalated to 10 mg p.o./day × 6 weeks) added to standard Gemcitabine and nab-Paclitaxel (GnP) chemotherapy in patients with locally advanced and/or metastatic PDAC. Markers of efficacy including Response Evaluation Criteria in Solid Tumors (RECIST 1.1) response, CT-based volumetric body composition measurements, and plasma chemistries for measuring metabolism and tumor burden were also analyzed. Results Of 23 patients who were screened, 15 enrolled. One expired (due to complications from underlying disease), 2 dropped out (did not tolerate GnP chemotherapy) during the first 4 weeks, and 12 completed. There were no unexpected or serious adverse events with dapagliflozin. One patient was told to discontinue dapagliflozin after 6 weeks due to elevated ketones, although there were no clinical signs of ketoacidosis. Dapagliflozin compliance was 99.4%. Plasma glucagon increased significantly. Although abdominal muscle and fat volumes decreased; increased muscle-to-fat ratio correlated with better therapeutic response. After 8 weeks of treatment in the study, partial response (PR) to therapy was seen in 2 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. After dapagliflozin discontinuation (and chemotherapy continuation), an additional 7 patients developed the progressive disease in the subsequent scans measured by increased lesion size as well as the development of new lesions. Quantitative imaging assessment was supported by plasma CA19-9 tumor marker measurements. Conclusions Dapagliflozin is well-tolerated and was associated with high compliance in patients with advanced, inoperable PDAC. Overall favorable changes in tumor response and plasma biomarkers suggest it may have efficacy against PDAC, warranting further investigation.

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SGLT2i increased the plasma fasting glucagon level in patients with diabetes: A meta-analysis

Cited by 5 publications

References 51 publications

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

Preliminary observations on the use of ertugliflozin in the management of hyperinsulinaemia and laminitis in 51 horses: A case series

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models

Safety, tolerability, and effectiveness of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin in combination with standard chemotherapy for patients with advanced, inoperable pancreatic adenocarcinoma: a phase 1b observational study

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