When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

Avogaro, Angelo; Delgado, Elías; Lingvay, Ildiko

doi:10.1002/dmrr.2981

Cited by 28 publications

(20 citation statements)

References 120 publications

(262 reference statements)

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“…DDP4 or SGLT2 inhibitors) [ 12 ]. Avogaro et al [ 52 ] showed in a meta-analysis of DPP4 inhibitors an apparently accepted mean increase in HbA 1c of 0.22% after 52 weeks of usage. Long-term loss of glycaemic control of 0.30% over 4 years of treatment was observed with dapagliflozin [ 53 ].…”

Section: Rationale For Timely Insulin Treatmentmentioning

confidence: 99%

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

Hanefeld

Fleischmann

Siegmund³

et al. 2020

Diabetes Ther

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Type 2 diabetes is characterised by chronic hyperglycaemia and variable degrees of insulin deficiency and resistance. Hyperglycaemia and elevated fatty acids exert harmful effects on bcell function, regeneration and apoptosis (gluco-lipotoxicity). Furthermore, chronic hyperglycaemia triggers a vicious cycle of insulin resistance, low-grade inflammation and a cascade of pro-atherogenic processes. Thus,

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Section: Rationale For Timely Insulin Treatmentmentioning

confidence: 99%

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

Hanefeld

Fleischmann

Siegmund³

et al. 2020

Diabetes Ther

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“…Considering their complementary physiological pathways, the combination of incretin‐based agents may prevent the rise in EGP and thus improve the hypoglycemic efficacy. Recent studies have confirmed a favourable role of these new classes of oral therapies over the conventional hypoglycemic agents in the treatment of T2DM and suggested a pleiotropic benefit when they were used in combination . What is more, each drug class has specific adverse effect (AE) profiles, and their combination has the potential to change respective side effect profiles or to mitigate or cause additive AEs, which still remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes

Zhou

Geng

Wang

et al. 2019

Diabetes Metabolism Res

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We aimed to determine whether sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and incretin-based agents combination therapy produces more benefits than SGLT2is alone in patients with type 2 diabetes mellitus (T2DM). PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) comparing SGLT2is plus Dipeptidyl-Peptidase 4 inhibitors (SGLT2is/DPP4is) or glucagon like peptide-1 receptor agonists (SGLT2is/GLP-1RAs) against SGLT2is as monotherapy or add-on to metformin in T2DMs. A total of 13 studies with 7350 participants were included. Combination with GLP-1RAs exhibited more HbA1c reduction (WMD: −0.8; 95% CI, −1.14 to −0.45%), weight loss (−1.46; 95% CI, −2.38 to −0.54 kg), and systolic blood pressure (SBP) reduction (−2.88; 95% CI, −4.52 to −1.25 mmHg) versus SGLT2is alone but increased the gastrointestinal disorder risk (RR: 1.68; 95% CI, 1.14-2.47). Combination with DPP4is exhibited an extra effect on HbA1c reduction (−0.47; 95% CI, −0.58 to −0.37%), a neutral effect on weight (0.19; 95% CI, −0.11 to 0.48 kg) and SBP (−0.01; 95% CI, −0.85 to 0.63 mmHg), and ameliorated the genital infections risk (0.73; 95% CI, 0.54-0.97) versus SGLT2is. Meta-regression indicated the hypoglycemic efficacy of SGLT2is/DPP4is is higher in Asians than in other ethnics, and the differences in BMI across ethnic groups may mediate this effect. SGLT2is and incretin-based agents combination therapy is efficacious and safe versus SGLT2is alone in T2DMs. Particularly, combination with GLP-1RAs shows additional benefits to glycemic, weight, and SBP control to a larger extent than DPP4is, while combination with DPP4is ameliorates the risk for genital infection seen with SGLT2is.We highlight the need for individualized treatment related to the selection of this novel combination therapy. KEYWORDSincretin-based agents, meta-analysis, SGLT2 inhibitors, type 2 diabetes

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“…Importantly, GLP‐1RAs and SGLT‐2 inhibitors have a different adverse event profile . Most of these events are infrequent, but yet they were significantly greater in the treatment groups compared to the placebo ones.…”

Section: Direct Evidences For New Anti‐diabetic Drugs Against CV Diseasementioning

confidence: 99%

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists

et al. 2019

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Bonaventura A, ). Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT-2 inhibitors and GLP-1 receptor agonists (Review). J Intern Med 2019; 286: 16-31.Patients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose-lowering therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose cotransporter (SGLT)-2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose-lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP-1RAs and SGLT-2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT-2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their 'pleiotropic' effects, specifically on heart failure, while GLP-1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP-1RAs and SGLT-2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.

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When metformin is not enough: Pros and cons of SGLT2 and DPP‐4 inhibitors as a second line therapy

Cited by 28 publications

References 120 publications

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update

Meta‐analysis on the efficacy and safety of SGLT2 inhibitors and incretin based agents combination therapy vs. SGLT2i alone or add‐on to metformin in type 2 diabetes

Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT‐2 inhibitors and GLP‐1 receptor agonists

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