The right place for metformin today

Schernthaner, Guntram; Schernthaner, Gerit-Holger

doi:10.1016/j.diabres.2019.107946

Cited by 52 publications

(35 citation statements)

References 71 publications

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“…The high prevalence of baseline metformin users in CVOTs of GLP‐1 RAs or SGLT‐2 inhibitors argues against this approach, as the benefits observed were in a population with high background metformin use. Thus, it is clearly of interest to assess cardiorenal outcomes in patients with versus those without baseline metformin use 15,16 …”

Section: Introductionmentioning

confidence: 99%

Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58

Cahn

Wiviott

Mosenzon

et al. 2020

Diabetes Obesity Metabolism

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Aim To assess the associations between baseline glucose‐lowering agents (GLAs) and cardiorenal outcomes with dapagliflozin versus placebo in the DECLARE‐TIMI 58 study. Materials and methods DECLARE‐TIMI 58 assessed the cardiorenal outcomes of dapagliflozin versus placebo in patients with type 2 diabetes. This post hoc analysis elaborates the efficacy and safety outcomes by baseline GLA for treatment effect and GLA‐based treatment interaction. Results At baseline, 14 068 patients (82.0%) used metformin, 7322 (42.7%) sulphonylureas, 2888 (16.8%) dipeptidyl peptidase‐4 inhibitors, 750 (4.4%) glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and 7013 (40.9%) insulin. Dapagliflozin reduced the composite of cardiovascular death (CVD) and hospitalization for heart failure (HHF) versus placebo regardless of baseline GLA, with greater benefit in the small group of patients with baseline use of GLP‐1 RAs (HR [95% CI] 0.37 [0.18, 0.78] vs. 0.86 [0.75, 0.98] in GLP‐1 RA users vs. non‐users, Pinteraction = .03). The overall HR for major adverse cardiovascular events (CVD, myocardial infarction or ischaemic stroke) was 0.93 (95% CI 0.84, 1.03) with dapagliflozin versus placebo, with no interaction by baseline GLA (Pinteraction > .05). The renal‐specific outcome was reduced with dapagliflozin versus placebo in the overall cohort (HR [95%CI] 0.53[0.43‐0.66]), with no interaction by baseline GLA (Pinteraction > .05). All of these outcomes were similar in those with versus those without baseline metformin use. Conclusions The effects of dapagliflozin on cardiorenal outcomes were generally consistent regardless of baseline GLA, with consistent benefits regardless of baseline metformin use. The potential clinical benefit of combining sodium‐glucose co‐transporter‐2 inhibitors with GLP‐1 RAs, given some evidence of cardiovascular risk reduction with both classes, should be explored further.

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Section: Introductionmentioning

confidence: 99%

Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58

Cahn

Wiviott

Mosenzon

et al. 2020

Diabetes Obesity Metabolism

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“…25 The short term goal of AGIs therapy is to reduce current level of blood glucose, the long term target is to diminish HbAIc (glycated haemoglobin) level. 10 Metformin and other biguanides such as phenformin on the other hand, precipitate lactic acidosis 9,11,12 and lactose intolerance-caused diarrhoea, 26 which of course, call for concern despite being effective even in the absence of functional pancreatic beta cells. The extract of C. roseus in the study showed antidiarrhoeal activity in the presence of both acarbose and metformin.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant and Anti-Proliferative Studies on Kigelia africana (Lam.) Benth. and its Constituents

2021

TJNPR

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The study conceptualized the sites and mechanisms of action as well as explored the interacting benefits of Catharanthus roseus (C. roseus) against the diarrhea-like toxicity associated with the hypoglycemic activity of acarbose and metformin using experimental rats. The diabetes was induced with alloxan. Diarrhoea was induced with castor oil (1 mL per rat) after 30 min of determining blood glucose levels of the different groups including additional Group VIII which received loperamide (3 mg/kg) serving as positive control. The sugar level was determined using a glucometer; while inhibition percent of faecal count and faecal weight were employed to determine antidiarrheal activity. All medicaments showed significant lowering of blood glucose levels when compared with control alone (P < 0.05) having the combination of extractmetformin-acabose extremely significant (P < 0.01), followed by extract-metformin. Also, significant antidiarrheal activity was shown in all groups treated with C. roseus, with highest percentage inhibition in fecal count 86.72% and fecal weight 89.78% exhibited by extractmetformin-acarbose combination compared to loperamide (86.74% and 81.17%, respectively). The extract of C. roseus enhances hypoglycemic efficacy and safety by significantly nullifying diarrheal-like adverse effects of acarbose and metformin.

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“…For these reasons, metformin was the baseline therapy in the majority of recent MACE outcome trials assessing the newer agents including GLP-1RA and SGLT2i therapies [43]. Hence, the cardiovascular benefits for SGLT2i and GLP-1RA therapy are seen mostly in individuals who were already taking metformin and we have limited information about the precise interaction of these relatively "newer" agents with metformin [97], which are unlikely to be detrimental.…”

Section: Thiazolidinediones (Tzds)mentioning

confidence: 99%

Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes?

et al. 2020

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Metformin is the most commonly used glucose-lowering therapy (GLT) worldwide and remains the first-line therapy for newly diagnosed individuals with type 2 diabetes (T2D) in management algorithms and guidelines after the UK Prospective Diabetes Study (UKPDS) showed cardiovascular mortality benefits in the overweight population using metformin. However, the improved Major Adverse Cardiovascular Events (MACE) realised in some of the recent large cardiovascular outcomes trials (CVOTs) using sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have challenged metformin’s position as a first-line agent in the management of T2D. Many experts now advocate revising the existing treatment algorithms to target atherosclerotic cardiovascular disease (ASCVD) and improving glycaemic control as a secondary aim. In this review article, we will revisit the major cardiovascular outcome data for metformin and include a critique of the UKPDS data. We then review additional factors that might be pertinent to metformin’s status as a first-line agent and finally answer key questions when considering metformin’s role in the modern-day management of T2D.

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The right place for metformin today

Cited by 52 publications

References 71 publications

Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58

Cardiorenal outcomes with dapagliflozin by baseline glucose‐lowering agents: Post hoc analyses from DECLARE‐TIMI 58

Antioxidant and Anti-Proliferative Studies on Kigelia africana (Lam.) Benth. and its Constituents

Where Does Metformin Stand in Modern Day Management of Type 2 Diabetes?

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