Dataset Information

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

ABSTRACT:

Aims/hypothesis

Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone.

Methods

Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest.

Results

In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63-1.35) vs rosiglitazone and 0.78 (0.53-1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86-1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94-1.88]).

Conclusions/interpretation

The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas.

SUBMITTER: Home PD

PROVIDER: S-EPMC2910882 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Publications

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

Home P D PD Kahn S E SE Jones N P NP Noronha D D Beck-Nielsen H H Viberti G G

Diabetologia 20100608 9

<h4>Aims/hypothesis</h4>Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed ...[more]

PMID: 20532476

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Project description:AimsThiazolidinediones are insulin sensitizers, and are associated with fluid retention and increased risk of heart failure (HF) in people with type 2 diabetes. We assessed fatal and non-fatal HF events and their outcome, and identified HF predictors in the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes) trial population.Methods and resultsIn a multicentre, open-label study, we randomized 4447 people with type 2 diabetes on metformin or sulfonylurea monotherapy with a mean HbA(1c) of 7.9% to add-on rosiglitazone (n = 2220) or to a combination of metformin and sulfonylurea (n = 2227) and followed them over 5.5 years on average. Heart failure hospitalizations and deaths were adjudicated by a Clinical Endpoint Committee using pre-specified criteria. Independent predictors of HF events were identified out of a group of 30 pre-specified clinical, demographic, and biological variables. In the rosiglitazone group, the risk of HF death or hospitalization was doubled: HR = 2.10 (95% CI, 1.35-3.27): the excess HF event rate was 2.6 (1.1-4.1) per 1000 person-years. An excess in HF deaths was observed (10 vs. two), including four HF deaths as first HF events. By contrast, there was no increase in cardiovascular mortality or hospitalization (HR = 0.99, 95% CI, 0.85-1.16) or in cardiovascular deaths (60 vs. 71). Independent predictors of HF were rosiglitazone assignment, age, urinary albumin : creatinine ratio, body mass index, and systolic blood pressure at baseline. A history of previous cardiovascular disease was not predictive of HF. Duration of HF hospitalization and rate of HF re-hospitalization were similar in the two groups.ConclusionThese findings confirm the increased risk of HF events in people treated with rosiglitazone and support the recommendation that this agent should not continue to be used in people developing symptomatic HF while using the medication. Close follow-up for the risk of HF should be offered to elderly people, people with markedly increased body mass index, people with microalbuminuria/proteinuria, and people with increased systolic blood pressure.

Dataset Information

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

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