Sodium–glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus

Scheen, André

doi:10.1038/s41574-020-0392-2

Cited by 213 publications

(134 citation statements)

References 251 publications

(389 reference statements)

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“…The most frequent AEs for henagliflozin were ketosis‐related events, which could be expected from the metabolic shift towards lipids and ketone bodies as energy fuel resulting from increased urine glucose excretion by the drug 25 . Importantly, most cases of ketosis were mild, with no case of DKA observed in our study, consistent with the low occurrence rate of DKA documented for other SGLT2 inhibitors 19 . The incidence of urinary tract infections was generally low and similar across the henagliflozin and placebo groups, consistent with a meta‐analysis of 86 randomized trials reporting that the risk of urinary tract infections was not increased with SGLT2 inhibitors compared with placebo or active control 26 .…”

Section: Discussionsupporting

confidence: 88%

“…25 Importantly, most cases of ketosis were mild, with no case of DKA observed in our study, consistent with the low occurrence rate of DKA documented for other SGLT2 inhibitors. 19 The incidence of urinary tract infections was generally low and similar across the henagliflozin and placebo groups, consistent with a meta-analysis of 86 randomized trials reporting that the risk of urinary tract infections was not increased with SGLT2 inhibitors compared with placebo or active control. 26 Notably, the incidence of genital infections, a common AE reported for SGLT2 inhibitors, was also low (<2%) across all treatment groups.…”

Section: Discussionsupporting

confidence: 78%

“…Nevertheless, our subgroup analysis showed a trend of greater reduction in HbA1c for henagliflozin 10 mg over 5 mg in patients with a baseline HbA1c of more than 8.5%. With their unique insulin‐independent mechanism of action, SGLT2 inhibitors have been widely shown to be effective both as monotherapy or as combined therapy with other glucose‐lowering drugs for treatment of T2D 19 . The role of henagliflozin as an add‐on therapy to metformin will be further elucidated in a separate phase 3 trial (NCT04390295).…”

Section: Discussionmentioning

confidence: 99%

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Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Li³

et al. 2021

Diabetes Obesity Metabolism

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Aim: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise.Materials and Methods: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period.Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks.Results: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were −0.91% (95% CI: −1.11% to −0.72%; P < .001) and −0.94% (−1.13% to −0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were −1.3 (−1.8 to −0.9) and −1.5 (−2.0 to −1.1) kg in body weight, and −5.1 (−7.2 to −3.0) and −4.4 (−6.5 to −2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred.Conclusions: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Li³

et al. 2021

Diabetes Obesity Metabolism

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“…The chronic hyperglycemic state contributes to oxidative stress by increasing levels of AGEs and ROS (46), increasing the risk of development of microvascular (retinopathy, nephropathy, and neuropathy), and macrovascular complications (congestive heart failure, stroke, coronary heart disease, myocardial infarction, and peripheral vascular disease) (42,47). These consequences result in a reduction in quality of life and life expectancy by even ten years among diabetic patients (42,48).…”

Section: Discussion Type II Diabetes Mellitus In a Nutshellmentioning

confidence: 99%

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

et al. 2021

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Diabetes mellitus (DM) is an ensemble of metabolic conditions that have reached pandemic proportions worldwide. Pathology’s multifactorial nature makes patient management, including lifelong drug therapy and lifestyle modification, extremely challenging. Currently, there is growing evidence about the effectiveness of using herbal supplements in preventing and controlling DM. Curcumin is a bioactive component found Curcuma longa, which exhibits several physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective, and anti-diabetic activities. For these reasons, our objective is to systematically review the effects of Curcuma longa or curcumin on DM. Databases such as PUBMED and EMBASE were searched, and the final selection included sixteen studies that fulfilled the inclusion criteria. The results showed that curcumin’s anti-diabetic activity might be due to its capacity to suppress oxidative stress and inflammatory process. Also, it significantly reduces fasting blood glucose, glycated hemoglobin, and body mass index. Nanocurcumin is also associated with a significant reduction in triglycerides, VLDL-c, total cholesterol, LDL-c, HDL-c, serum C reactive protein, and plasma malonaldehyde. Therefore, it can be considered in the therapeutic approach of patients with DM.

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“…Diabetes is a serious chronic metabolic disorder affecting 463 million of individuals worldwide in 2019, and a further 700 million likely to be added by 2045 1 . Additionally, numerous epidemiological studies have shown that diabetes is not only closely related to blindness, limb amputations, and renal failure, but also an independent risk factor for peripheral artery disease [2][3][4] . Indeed, diabetes can be categorized into two types: T1D is mainly caused by insu cient insulin secretion, and T2D is abnormal insulin secretion and/or non-insulin-dependent diabetes, complicated by postprandial hyperglycemia 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Bioactivity-Guided Separation of Potential α-glycosidase Inhibitor from Clerodendranthus Spicatus based on HSCCC with Molecular Docking

Zhu

Niu

Nie

et al. 2020

Preprint

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Clerodendranthus Spicatus is a traditional Dais medi-edible plant and it has been proven to have good blood glucose-lowering efficacy. However, the material basis of Clerodendranthus Spicatus has not been clarified yet. Therefore, in this paper, the compounds were purified by high-speed counter-current chromatography (HSCCC) and the potential activity of compounds were determined by molecular docking. In the separation process, the solvent system was determined by a 9 × 9 map-based solvent selection strategy and the solvent system hexane/ethyl acetate/methanol/water (3:5:3:5, v/v) was used for HSCCC. Finally, five compounds were purified and identified as 2-Caffeoyl-L-tartaric acid (1), N-(E)-caffeoyldopamine (2), rosmarinc acid (3), Methyl rosmarinate (4), 6,7,8,3',4'-Pentamethoxyflavone (5). Then, the identified compounds were individually docked with α-glycosidase. The affinity energies of the identified compounds ranged from -7.6 to -8.6 kcal/mol, which are all better than acarbose (-6.6 kcal/mol). In particularly, rosmarinc acid with the lowest affinity energy of -8.6 kcal/mol was wrapped by the active site of α-glycosidase. The docking results indicated that the target compounds have potential α-glycosidase inhibitory activity and may be responsible for the blood glucose-lowering activity of Clerodendranthus Spicatus. The results indicated that the bioactivity-guided method is practical for the effective separation of active compounds from natural resources.

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Sodium–glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus

Cited by 213 publications

References 251 publications

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double‐blind, placebo‐controlled, phase 3 trial

The Effects of Curcumin on Diabetes Mellitus: A Systematic Review

Bioactivity-Guided Separation of Potential α-glycosidase Inhibitor from Clerodendranthus Spicatus based on HSCCC with Molecular Docking

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