Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes

Johnson, Jeffrey; Simpson, Scot H.; Toth, Ellen L.; Majumdar, Sumit R.

doi:10.1111/j.1464-5491.2005.01448.x

Cited by 144 publications

(117 citation statements)

References 28 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…These findings are in contrast to those reported by Olsson and co-workers [7], also referred to by Tayek in his letter [1]. Although Olsson and colleagues reported that mortality was increased in diabetic patients given a combination of sulfonylurea and metformin compared with those patients given sulfonylurea alone, this study involved far fewer patients than the study by Johnson et al [6]. Moreover, Olsson et al [7] state that the observed increased mortality in the combination group may be secondary to a more aggressive type of diabetes.…”

contrasting

confidence: 55%

“…This finding is difficult to interpret as patients given higher doses of oral glucose-lowering therapies may have presented with worse glycaemia and/or more advanced type 2 diabetes, which are confounding factors. The same group of investigators demonstrated in another two studies [5,6] using the same database that, compared with sulfonylurea monotherapy, the combination of sulfonylurea and metformin is associated with a reduced risk of mortality. These findings are in contrast to those reported by Olsson and co-workers [7], also referred to by Tayek in his letter [1].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

Raccah

2007

Diabetologia

View full text Add to dashboard Cite

contrasting

confidence: 55%

mentioning

confidence: 99%

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

Raccah

2007

Diabetologia

View full text Add to dashboard Cite

“…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: 96%

Metformin: historical overview

2017

View full text Add to dashboard Cite

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.

show abstract

“…Our findings, which controlled for many potential confounding variables, found no significant increase in mortality associated with metformin used alone or in combination with sulfonylureas. Recently, studies published by Johnson and colleagues (7,20) concluded that metformin alone and in combination was associated with a reduced risk of mortality. Our sample size and duration of follow-up may have limited our ability to detect any potential beneficial effect of drug therapy on allcause mortality.…”

mentioning

confidence: 99%

Impact of Oral Antihyperglycemic Therapy on All-Cause Mortality Among Patients With Diabetes in the Veterans Health Administration

Kahler

Rajan

Rhoads³

et al. 2007

Diabetes Care

View full text Add to dashboard Cite

OBJECTIVE -The objective of this analysis was to evaluate the impact of several classes of oral antihyperglycemic therapy relative to sulfonylurea monotherapy on all-cause mortality among a cohort of patients with diabetes from the Veterans Health Administration (VHA). RESEARCH DESIGN AND METHODS-A retrospective cohort study using data obtained from the VHA Diabetes Epidemiology Cohort was used. Users of oral antihyperglycemic therapy were classified into the following cohorts: sulfonylurea monotherapy, metformin monotherapy, metformin plus sulfonylurea, thiazolidinedione (TZD) use alone or in combination with other oral agents (TZD users), and no drug therapy. All-cause mortality was the outcome of interest. Multivariate mixed models incorporating a propensity score to account for imbalance among cohorts were used to estimate drug effects on mortality with associated 95% CIs.RESULTS -A total of 39,721 patients with diabetes were included in the study. Adjusted odds ratios and 95% CIs for all-cause mortality were 0.87 (0.68 -1.10) for metformin monotherapy users, 0.92 (0.82-1.05) for metformin plus sulfonylurea users, and 1.04 (0.75-1.46) for TZD users, relative to sulfonylurea monotherapy users.CONCLUSIONS -We did not find any significant drug effect on all-cause mortality for any oral treatment cohorts relative to sulfonylurea oral monotherapy. Diabetes Care 30:1689-1693, 2007T he most influential study designed to assess long-term microvascular and macrovascular outcomes in patients with type 2 diabetes was the U.K. Prospective Diabetes Study (UKPDS). It was specifically designed to assess the effects of intensive glycemic control versus a more liberal treatment target on the cardiovascular and microvascular complications of type 2 diabetes (1,2). Despite several shortcomings (3), the UKPDS answered the question of whether intensive blood glucose control is beneficial for people with type 2 diabetes and found that it definitely is, especially with regard to microvascular complications (2). However, the UKPDS was less conclusive regarding the impact of specific oral antihyperglycemic treatments targeting a lower A1C level on the risk of macrovascular complications and all-cause mortality. Furthermore, thiazolinediones (TZDs) were not available during the time period of the UKPDS.Since the publication of the primary findings from the UKPDS, several observational studies conducted in Europe and Canada have assessed the effect of diabetes drug treatment on mortality but have produced conflicting results (4 -8). A commonality across most of the observational studies conducted to date is that it has been difficult to draw conclusions because of the high potential for confounding by indication (i.e., the tendency for patients with more severe disease both to be exposed to more aggressive therapy and to be more likely to experience an adverse outcome). The direct effect of drug exposure also has been difficult to ascertain because many of the long-term studies assessed drug exposure only once and then assessed mortal...

show abstract

Reduced cardiovascular morbidity and mortality associated with metformin use in subjects with Type 2 diabetes

Abstract: Metformin monotherapy was associated with a lower risk of cardiovascular-related morbidity and mortality, and combination metformin and sulphonylurea therapy was associated with a reduced risk of fatal cardiovascular events, when compared with sulphonylurea monotherapy.

Cited by 144 publications

References 28 publications

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

Comment on: Evans JMM, Ogston SA, Emslie-Smith A, Morris AD (2006) Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 49:930–936

Metformin: historical overview

Impact of Oral Antihyperglycemic Therapy on All-Cause Mortality Among Patients With Diabetes in the Veterans Health Administration

Contact Info

Product

Resources

About