Improved Clinical Outcomes Associated With Metformin in Patients With Diabetes and Heart Failure

Eurich, Dean T.; Majumdar, Sumit R.; McAlister, Finlay A.; Tsuyuki, Ross T.; Johnson, Jeffrey

doi:10.2337/diacare.28.10.2345

Cited by 369 publications

(265 citation statements)

References 46 publications

(37 reference statements)

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“…Reduced cardiovascular risk appeared to be largely independent of glucose-lowering efficacy and attention is drawn to a substantial literature noting potentially advantageous effects of the drug on the macro-and microvasculature (Table 3) [70,71]. Interrogation of large databases that captured longterm treatment of type 2 diabetes consistently confirmed the reduced cardiovascular risk with metformin, and a 10-year follow-up of the UKPDS in 2008 showed a continued cardiovascular benefit of early use of the drug [72][73][74].…”

Section: The Ukpds and Long-term Retrospective Studiesmentioning

confidence: 97%

Metformin: historical overview

2017

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Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications.

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Section: The Ukpds and Long-term Retrospective Studiesmentioning

confidence: 97%

Metformin: historical overview

2017

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“…A reduction in deaths or hospitalizations was also observed: for metformin monotherapy HR=0.83 ; 0.70-0.99 and for combination therapy HR=0.86 ; 0.77-0.96). Thus, metformin, alone or in combination, in subjects with T2DM and CHF was associated with lower morbidity and mortality compared with sulfonylurea monotherapy [40].…”

Section: Metformin In Patients With Congestive Heart Failurementioning

confidence: 99%

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Scheen

Paquot

2013

Diabetes & Metabolism

143

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Metformin is unanimously considered as the first-line glucose-lowering agent. Theoretically, however, it cannot be prescribed in a large proportion of patients with type 2 diabetes because of the presence of numerous contraindications corresponding to situations that may increase the risk of lactic acidosis. Various observational data from real life showed that many diabetic patients considered as "at risk" still receive metformin, often without appropriate dose adjustment, apparently without any harm, especially no increased risk of lactic acidosis. More interestingly, recent data suggest that type 2 diabetes patients who are considered as being "at risk" because of the presence of traditional contraindications still take benefit from metformin therapy, with a reduction of morbidity and mortality compared with other glucose-lowering agents, more particularly sulfonylureas. The present review analyzes the benefit-risk balance of metformin therapy in special populations, namely patients with stable coronary artery disease, acute coronary syndrome or myocardial infarction, congestive heart failure, renal impairment or chronic kidney disease, hepatic dysfunction and chronic respiratory insufficiency, all conditions that may theoretically increase the risk of lactic acidosis. A special attention will be devoted to elderly patients with type 2 diabetes. Indeed, this population is growing rapidly and older patients may cumulate several comorbidities

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“…However, the incidence of lactic acidosis due to metformin treatment even in high-risk patients, i.e. patients with heart failure, having procedures requiring iodinated contrast, and/or patients with renal impairment, seems to be very small (33), and data actually suggest that metformin is associated with improved survival in heart failure patients (34).…”

Section: Discussionmentioning

confidence: 99%

Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes

Andersson

Søgaard²,

Hoffmann³

et al. 2010

European Journal of Endocrinology

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Objective: To examine the association between selected glucose-lowering medications and left ventricular (LV) diastolic function in patients with diabetes. Design: Retrospective cohort study (years 2005-2008). Methods: Echocardiograms of 242 patients with diabetes undergoing coronary angiography were analyzed. All patients had an LV ejection fraction (LVEF) R20% and were without atrial fibrillation, bundle branch block, valvular disease, or cardiac pacemaker. Patients were grouped according to the use of metformin (nZ56), sulfonylureas (nZ43), insulin (nZ61), and combination treatment (nZ82). Results: Mean age (66G10 years) and mean LVEF (45G11%) were similar across the groups. Mean isovolumic relaxation time (IVRT) was 66G31, 79G42, 69G23, and 66G29 ms in metformin, sulfonylureas, insulin, and combination treatment groups respectively (PZ0.4). Mean early diastolic longitudinal tissue velocity (e 0 ) was 5.3G1.6, 4.6G1.6, 5.3G1.8, and 5.4G1.7 cm/s in metformin, sulfonylureas, insulin, and combination treatment groups (PZ0.04). In adjusted linear regression models, the use of metformin was associated with a shorter IVRT (parameter estimate K9.9 ms, PZ0.049) and higher e 0 (parameter estimate C0.52 cm/s, PZ0.03), compared with no use of metformin. The effects of metformin were not altered by concomitant use of sulfonylureas or insulin (P for interactions O0.4). Conclusions: The use of metformin is associated with improved LV relaxation, as compared with no use of metformin.

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Improved Clinical Outcomes Associated With Metformin in Patients With Diabetes and Heart Failure

Cited by 369 publications

References 46 publications

Metformin: historical overview

Metformin: historical overview

Metformin revisited: A critical review of the benefit–risk balance in at-risk patients with type 2 diabetes

Metformin is associated with improved left ventricular diastolic function measured by tissue Doppler imaging in patients with diabetes

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