Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study

Gulliford, Martin; Latinovic, Radoslav

doi:10.1002/dmrr.457

Cited by 62 publications

(51 citation statements)

References 19 publications

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“…Combination cohort patients also had an increased risk of cardiovascular hospital admission. These results conflict with those from a previous study that, using the UK General Practice Research Database [9], found no increased risk of mortality in combination cohorts compared with patients prescribed drugs singly. However, it is important to recognise that these cohorts represent a heterogeneous mix of patients, with widely varying levels of exposure to sulfonylureas and metformin.…”

Section: Discussioncontrasting

confidence: 99%

“…Observational studies have shown increased risks associated with a combination of metformin and sulfonylureas, but have been unable to account fully for underlying differences between patients in different therapy groups [7,8]. In contrast, a more recent study found no increased risk of mortality among patients who were prescribed sulfonylureas and metformin in combination, compared with those prescribed either drug as monotherapy [9].…”

Section: Introductionmentioning

confidence: 98%

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Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

et al. 2006

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Aims/hypothesis: The aim of this study was to evaluate the risk of adverse cardiovascular outcomes in patients with type 2 diabetes newly treated with sulfonylureas and metformin. Subjects and methods: The Diabetes Audit and Research in Tayside Scotland (DARTS) diabetes information system and the Medicines Monitoring Unit (MEMO) dispensed prescribing database for the population of Tayside, Scotland (400,000 people) were employed. Patients newly prescribed with oral hypoglycaemic agents between 1994 and 2001 were classified into five study cohorts according to the treatment received: metformin only, sulfonylureas only, sulfonylureas added to metformin, metformin added to sulfonylureas, and both drugs simultaneously. In Cox regression analyses, we estimated relative risks for all-cause mortality, cardiovascular mortality and cardiovascular hospital admission for patients in the five study cohorts, with metformin monotherapy as the reference group. Results: Of the 5,730 study patients, 1,000 died during a maximum of 8 years follow-up. Patients in the sulfonylureas only cohort had increased risks of mortality and cardiovascular mortality, with unadjusted relative risks of 3.12 (95% CI 2.54-3.84) and 3.71 (95% CI 2.64-5.22), respectively. After adjusting for differences between groups (age, sex, duration of diabetes, blood pressure, cholesterol, HbA 1c , smoking, previous hospital admission, treatment with cardiovascular medication), these relative risks were 1.43 (95% CI 1.15-1.77) and 1.70 (95% CI 1.18-2.45), respectively. Patients in the combination cohorts had significantly increased risks of cardiovascular hospital admission, as well as increased risks of mortality and cardiovascular mortality. Conclusions/interpretation: In this cohort study of patients newly treated with oral hypoglycaemic agents, those treated with sulfonylureas only, or combinations of sulfonylureas and metformin, were at higher risk of adverse cardiovascular outcomes than those treated with metformin alone.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

et al. 2006

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“…However, these results have not been confirmed by other studies (9,10,11), and either reduced (12,13,14) or increased all-cause or CV mortality has been reported in patients treated with sulphonylureas (15,16). Furthermore, although metformin has been shown to consistently reduce the risks of cancer incidence and mortality (17), the data concerning sulphonylureas are controversial because a neutral effect (14,18,19), an increased risk (20,21,22,23) and a reduced cancer-related mortality (24) have been described in the literature.…”

Section: Introductionmentioning

confidence: 83%

“…Furthermore, not all studies evaluated glibenclamide separately from other sulphonylureas but considered 'second-generation' sulphonylureas (13), or 'old sulphonylureas' (35), or 'sulphonylureas' alone (7,8,9,10,11,14,20). The possibility that the sulphonylureas are not equal in terms of all-cause mortality risk or CV risk had already been raised (1,2,3,4,5,12,13,15,25,26,27,28,29).…”

Section: Glibenclamidementioning

confidence: 99%

Mortality outcomes of different sulphonylurea drugs: the results of a 14-year cohort study of type 2 diabetic patients

Castiglione

Ghigo

et al. 2013

European Journal of Endocrinology

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Objective: Available data about mortality of type 2 diabetic patients treated with different sulphonylureas are scarce and contradictory. Design: We evaluated the associations between all-cause and cause-specific mortality and treatments with different sulphonylureas in a retrospective cohort of type 2 diabetic patients from a diabetes clinic. Methods: All 1277 patients treated with sulphonylureas during 1996-1997 were enrolled: 159 patients were treated with tolbutamide, 977 glibenclamide and 141 gliclazide. The baseline data (centralised laboratory parameters, anthropometric data and presence of chronic complications) were abstracted from the clinical records. Information on vital status was collected from demographic files after 14-year follow-up. Adjusted hazard ratios (HR) were estimated with Cox (all-cause mortality) or Fine and Gray models (cause-specific mortality), including several potential confounders. Results: Five hundred and fifty-six patients died during the follow-up: 262 from cardiovascular causes, 158 from cancer and 136 from other causes. When compared with the glibenclamide users, the gliclazide and tolbutamide users showed a significantly lower cancer mortality (HRZ0.30; 95% CI 0.16-0.55, and HRZ0.48; 95% CI 0.29-0.79 respectively). These results were strongly confirmed in the 555 patients on sulphonylurea monotherapy. None of the patients who were treated with gliclazide monotherapy died from cancer during the follow-up, and the patients on tolbutamide treatment exhibited a lower cancer mortality than the glibenclamide users (HRZ0.40; 95% CI 0.22-0.71). Data did not change after stratification for the duration of sulphonylurea treatment from diabetes diagnosis to the study enrolment. Conclusions: Cancer mortality was markedly reduced in the patients on gliclazide and tolbutamide treatment. These results suggest additional benefits for these drugs beyond their blood glucoselowering effect and strongly advocate for further investigation.

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“…Так, исследование, проведенное в Великобритании, основывалось на общенациональном регистре, обоб-щающем данные 263 врачей общей практики [29]. Кроме характера медикаментозного лечения учитывался возраст больного в начале медикаментозной тера-пии, пол, время начала терапии, наличие ИБС или при-ем сердечно-сосудистых препаратов.…”

Section: сердечно-сосудистые последствия сахароснижающей терапииunclassified

Reduction of Cardiovascular Complications of Modern Hypoglycemic Therapy of Diabetes Mellitus Type 2: "Florentine Heresy"

Александров¹

2010

Racionalʹnaâ farmakoterapiâ v kardiologii

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Эндокринологический научный центр. 117036, Москва, ул. Дмитрия Ульянова, 11Снижение сердечно-сосудистых осложнений современной сахароснижающей терапии сахарного диабета 2 типа: «флорентийская ересь» А.А. Александров* Эндокринологический научный центр. 117036, Москва, ул. Дмитрия Ульянова, 11Классические гипогликемические препараты включают бигуаниды, препараты сульфонилмочевины, меглитиниды, глитазоны и ингибиторы альфа-глюкозидазы. Современный алгоритм гипогликемической терапии на первой ступени предполагает изменение образа жизни и монотерапию метформином, на второй ступени -комбинированную терапию. Однако влияние комбинаций сахароснижающих препаратов на долгосрочный сердечно-сосудистый прогноз у пациентов с сахарным диабетом 2 типа изучено недостаточно. Ком-бинированная терапия глибенкламидом и метформином может иметь неблагоприятные сердечно-сосудистые эффекты, в связи с чем необходимо избегать длительного ее при-менения у пациентов с коронарной болезнью сердца и разработать адекватные фармакологические подходы к коррекции гипергликемии. Ключевые слова: сахарный диабет, комбинированная гипогликемическая терапия, метформин, препараты сульфонилмочевины. The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step -the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

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Mortality in type 2 diabetic subjects prescribed metformin and sulphonylurea drugs in combination: cohort study

Abstract: In this large non-randomized study, there was no evidence of increased mortality risk following prescription of sulphonylurea and metformin in combination, as compared to either drug prescribed singly.

Cited by 62 publications

References 19 publications

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin

Mortality outcomes of different sulphonylurea drugs: the results of a 14-year cohort study of type 2 diabetic patients

Reduction of Cardiovascular Complications of Modern Hypoglycemic Therapy of Diabetes Mellitus Type 2: "Florentine Heresy"

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