Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes

Vasilakou, Despoina; Karagiannis, Thomas; Athanasiadou, Eleni; Mainou, Maria; Liakos, Aris; Bekiari, Eleni; Sarigianni, Maria; Matthews, David R.

doi:10.7326/0003-4819-159-4-201308200-00007

Cited by 829 publications

(773 citation statements)

References 42 publications

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“…Because of their mode of action, SGLT-2 inhibitors can be combined with any other glucose-lowering agent [18] . PD investigations and clinical studies have shown complementary efficacy in reducing fasting and postprandial glucose and glycated haemoglobin (HbA 1c ) levels.…”

Section: Drug-drug Interactions With Other Glucose-lowering Agentsmentioning

confidence: 99%

“…SGLT2 inhibitors may be used as monotherapy in diet-treated patients or in combination with any other glucose-lowering agent [18] . PK characteristics of SGLT2 inhibitors show an excellent oral bioavailability, a rather long half-life allowing once daily administration, a low accumulation index, no active metabolites and a negligible renal clearance (Table 1) [19] .…”

Section: Introductionmentioning

confidence: 99%

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Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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SUMMARYInhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure (assessed by peak plasma concentrations -C max -and area under the concentrationtime curve -AUC -) to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin.Some modest changes were not considered as clinically relevant. However, drugs which could specifically interfere with the metabolic pathways of SGLT2 inhibitors (rifampin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase -UGT -) may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin.Potential drug-drug interactions in patients with type 2 diabetes receiving a chronic treatment with a SGLT2 inhibitor deserve further attention, especially in the numerous individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

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Section: Drug-drug Interactions With Other Glucose-lowering Agentsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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“…즉, SGLT2 억제제가 근위세뇨관 에서 과흡수를 억제하면 원위세뇨관으로 나트륨 전달이 증가하고 염분의 증가가 macula densa에서 감지되면 afferent arteriole을 수축시키는 tubuloglomerular feedback이 작동하여 사구체의 과여과가 개선되어 사구 체여과율이 감소하며 당뇨병 환자에서 empagliflozin 투여에 의한 과여과의 감소 정도는 레닌-안지오텐신-알도스테론 축(renin-anigotensin-aldosterone system, 이하 RAAS)의 억제 효과와 비슷할 정도라고 보고되었다( Fig. 1) [19]. 당뇨병 환자에서 SGLT2 투여 후 소변으로 포도당 배설은 1일 약 70 그램 정도 배설되므로 이에 의 한 칼로리 소실과 삼투압성 이뇨에 의한 체액 감소가 기 여할 것으로 여겨진다 [20].…”

Section: 근위세뇨관에서의 과흡수 (Hyperreabsorption)와 Tubuloglomerular Feedback의unclassified

“…체중감소를 조사한 연구 결과들에 의하면 CANTATA-SU 연구에서는 Canagliflozin 100 mg/일(-3.7 kg) 혹은 300 mg/일(-4.0 kg) 투여군에서 glimepiride 투 여군(+0.7 kg)에 비해서 52주째 체중변화가 유의하게 감소되었는데 canagliflozin 투여군에서는 2/3 정도의 체중감소는 체지방감소가, 1/3 정도의 체중감소는 지방 조직 외 조직의 감소가 기여하였고 전산화단층촬영 분 석에서는 복부지방 감소가 피하지방감소보다 더 저명하 였다 [19].…”

Section: 근위세뇨관에서의 과흡수 (Hyperreabsorption)와 Tubuloglomerular Feedback의unclassified

The Non-glycemic Effects of SGLT2 Inhibitor

Lee

2014

J Korean Diabetes

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Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been introduced as a new class of antidiabetic agents. In addition to their glycemic action, SGLT2 inhibitors also have a number of non-glycemic effects that may contribute to renal and/or cardiovascular benefits. These include effects on tubuloglomerular feedback in the kidney, body weight, blood pressure, and serum uric acid. Other non-glycemic effects of SGLT2 inhibitors that need to be further studied include the effects on lipid profiles, food intake, and secretion of hormones such as leptin, incretins, and aldosterone. Also, the exact mechanisms of various non-glycemic actions should be further studied. Additionally, SGLT2 inhibitor therapy in combination with other drugs may have beneficial glycemic and non-glycemic effects. (

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“…Weight reduction and sodium depletion also contribute to this finding. 23,24 In addition, a direct vascular effect, with reduced arterial stiffness, leads to BP change. 25 The effect of this class on serum lipid levels is mild.…”

Section: The Kidney As a Treatment Targetmentioning

confidence: 99%

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

Santos¹,

Lima

Sousa‐Rodrigues³

et al. 2017

Rev. Assoc. Med. Bras.

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Summary Introduction: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. Objective: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile. Method: A literature search on Pubmed database was performed using the following keywords: "SGLT-2 inhibitors," "dapagliflozin," "empagliflozin," "canagliflozin." Results: SGLT-2 inhibitors are a class of oral antidiabetic drugs directed to the kidney. Their mechanism of action is to reduce blood glucose by inducing glycosuria. Extra-glycemic benefits have been described, such as weight loss, decline in blood pressure and levels of triglycerides and uric acid, and they can slow the progression of kidney disease. Genitourinary infections are the main side effects. There is a low risk of hypotension and hypoglycemia. Diabetic ketoacidosis is a serious adverse effect, although rare. Empagliflozin has already had its cardiovascular benefit demonstrated and studies with other drugs are currently being performed. Conclusion: SGLT-2 inhibitors are a new treatment option for type 2 diabetes mellitus, acting independently of insulin. They have potential benefits other than the reduction of blood glucose, but also carry a risk for adverse effects.

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Sodium–Glucose Cotransporter 2 Inhibitors for Type 2 Diabetes

Abstract: None.

Cited by 829 publications

References 42 publications

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

The Non-glycemic Effects of SGLT2 Inhibitor

Use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus

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