SGLT2 versus DPP4 inhibitors for type 2 diabetes

Scheen, André

doi:10.1016/s2213-8587(13)70095-0

Cited by 22 publications

(13 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 19 , 169 However, from the point of view of the endocrinologist, both DPP-4 and SGLT-2 inhibitors have advantages and disadvantages so that a personalized approach based on the properties of the medication and the individual characteristics of the patient is the recommended best approach (Table 7 ). 170 The use of glucose-lowering medications should be optimized according to a patient-centered approach, and the emergence of precision medicine may help to have a better strategy for the management of T2DM in the future. 171 …”

Section: Personalized Approach: Dpp-4 or Sglt-2 Inhibitor?mentioning

confidence: 99%

Cardiovascular Effects of New Oral Glucose-Lowering Agents

Scheen

2018

Circulation Research

233

157

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is a major challenge in the management of type 2 diabetes mellitus. Glucose-lowering agents that reduce the risk of major cardiovascular events would be considered a major advance, as recently reported with liraglutide and semaglutide, 2 glucagon-like peptide-1 receptor agonists, and with empagliflozin and canagliflozin, 2 SGLT-2 (sodium-glucose cotransporter type 2) inhibitors, but not with DPP-4 (dipeptidyl peptidase-4) inhibitors. The present review is devoted to CV effects of new oral glucose-lowering agents. DPP-4 inhibitors (gliptins) showed some positive cardiac and vascular effects in preliminary studies, and initial data from phase 2 to 3 clinical trials suggested a reduction in major cardiovascular events. However, subsequent CV outcome trials with alogliptin, saxagliptin, and sitagliptin showed noninferiority but failed to demonstrate any superiority compared with placebo in patients with type 2 diabetes mellitus and high CV risk. An unexpected higher risk of hospitalization for heart failure was reported with saxagliptin. SGLT-2 inhibitors (gliflozins) promote glucosuria, thus reducing glucose toxicity and body weight, and enhance natriuresis, thus lowering blood pressure. Two CV outcome trials in type 2 diabetes mellitus patients mainly in secondary prevention showed remarkable positive results. Empagliflozin in EMPA-REG-OUTCOME (EMPAgliflozin Cardiovascular OUTCOME Events in Type 2 Diabetes Mellitus Patients) reduced major cardiovascular events, CV mortality, all-cause mortality, and hospitalization for heart failure. In CANVAS (Canagliflozin Cardiovascular Assessment Study), the reduction in CV mortality with canagliflozin failed to reach statistical significance despite a similar reduction in major cardiovascular events. The underlying protective mechanisms of SGLT-2 inhibitors remain unknown and both hemodynamic and metabolic explanations have been proposed. CVD-REAL studies (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors; with the limitation of an observational approach) suggested that these favorable results may be considered as a class effect shared by all SGLT-2 inhibitors (including dapagliflozin) and be extrapolated to a larger population of patients with type 2 diabetes mellitus in primary prevention. Ongoing CV outcome trials with other DPP-4 (linagliptin) and SGLT-2 (dapagliflozin, ertugliflozin) inhibitors should provide additional information about CV effects of both pharmacological classes.

show abstract

Section: Personalized Approach: Dpp-4 or Sglt-2 Inhibitor?mentioning

confidence: 99%

Cardiovascular Effects of New Oral Glucose-Lowering Agents

Scheen

2018

Circulation Research

233

157

View full text Add to dashboard Cite

show abstract

“…Despite the complementary mechanisms of DPP-4i and SGLT2i, it is thus difficult to systematically recommend the initiation of a combined therapy after failure of metformin monotherapy. The question that thus arises is which of the two pharmacological agents should be added first, either SGLT2i or DPP-4i, in T2D patients who do not reach individual HbA1c targets with metformin [55]. According to the results of a recent systematic review and network meta-analysis of clinical trials and compared to DPP-4i, almost similar reductions in HbA1c were reported with dapagliflozin and empagliflozin but a greater reduction in HbA1c was observed with canagliflozin, especially at the dosage of 300 mg [10].…”

Section: Expert Opinionmentioning

confidence: 99%

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Scheen

2016

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

SUMMARYIntroduction : Type 2 diabetes (T2D) is a complex disease with multiple defects, which generally require a combination of several pharmacological approaches to control hyperglycemia. Combining a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGT2i) appears to be an attractive approach.Area covered: An extensive literature search was performed to analyze the pharmacokinetics, pharmacodynamics and clinical experience of different gliptin-gliflozin combinations.Expert opinion: There is a strong rationale for combining a DPP-4i and a SGLT2i in patients with T2D because the two drugs exert different and complementary glucose-lowering effects.Dual therapy (initial combination or stepwise approach) is more potent than either monotherapy in patients treated with diet and exercise or already treated with metformin.Combining the two pharmacological options is safe and does not induce hypoglycemia. The additional glucose-lowering effect is more marked when a gliflozin is added to a gliptin than when a gliptin is added to a gliflozin. Two fixed-dose combinations (FDCs) are already available (saxagliptin-dapagliflozin and linagliptin-empagliflozin) and others are in current development. Bioequivalence of the two compounds given as FDC tablets was demonstrated when compared with coadministration of the individual tablets. FDCs could simplify the antihyperglycaemic therapy and improve drug compliance. Article highlights box -Type 2 diabetes (T2D) often requires the combination of several medications with complementary actions to reach glucose control targets while limiting side effects -The combination of a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) is an attractive approach for the management of T2D. Keywords-Both saxagliptin plus dapagliflozin and linagliptin plus empagliflozin combined therapies have been tested as separate tablets (no clinically relevant pharmacokinetic drug-drug interactions) and as fixed-dose combination (FDC : bioequivalence studies).-DPP-4i -SGLT2i combined therapies are more efficacious than either monotherapy to control blood glucose, without worsening of the safety profile.-Initial DPP-4i -SGLT2i combination may be considered or one compound may the added to the other. However, which one should be used in first place remains an open question.

show abstract

“…or background SU plus metformin therapy (Schernthaner et al .). [20] There was no significant difference among this agent in A1c reduction but SGLT2I were associated with consistent weight loss and BP reduction. In fact in one study, canagliflozin 300 mg was superior to sitagliptin 100 mg [Table 11].…”

Section: Second-line Oral Drugs After Metformin: Options Left Openmentioning

confidence: 95%

Deciding oral drugs after metformin in type 2 diabetes: An evidence-based approach

Singh

2014

Indian J Endocr Metab

View full text Add to dashboard Cite

SGLT2 versus DPP4 inhibitors for type 2 diabetes

Cited by 22 publications

References 9 publications

Cardiovascular Effects of New Oral Glucose-Lowering Agents

Cardiovascular Effects of New Oral Glucose-Lowering Agents

DPP-4 inhibitor plus SGLT-2 inhibitor as combination therapy for type 2 diabetes: from rationale to clinical aspects

Deciding oral drugs after metformin in type 2 diabetes: An evidence-based approach

Contact Info

Product

Resources

About